Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 DOI 10.1007/s11739-011-0736-y

Posters

Saturday, October 22nd 2011 Allergology and Clinical Immunology Cough, oedema and fever in a patient with ventriculo-atrial shunt M. Ammendola, G. Tarquini, B. Ciccantelli, S. Da Ros, L. Lamartina, M. Sellini, P. Lucia, S. Matteoli Dipartimento di Medicina Interna e Specialita` Mediche, Universita` di Roma Sapienza, Roma, Italy A 38 year old woman came to our attention with columnar lower limbs oedema and developed over the three days before, macrohematuria since twenty days before, anemia, hypoalbuminemia and lowered values of all serum electrolytes. Renal function was in normal range. A modest cognitive slowing was present. A past history of congenital hydrocephalus, with several ventriculo atrial shunts changed over time, with residual mental retardation, was reported. A fractious cough since she was 6 years old after one of the shunt removals, a slight anemia detected a year before referred. No changes in her usual home therapy was made in the last years (antiepileptic and iron therapy). A renal problem related to a nephrotic syndrome was early suspected since concomitance of signs and symptoms noticed and the blood tests results. A medical therapy was started with low molecular weight heparin, diuretic, ACE-inhibitor, angiotensin II receptor antagonist and low protein diet. Even if medical therapy was started a worsening of oedema and of renal function was seen. Etiological diagnosis was still to be determined. We started excluding secondary causes of nephrotic syndrome. Anamnesis, first and second level exams excluded: Diabetes Mellitus, drug toxicity, amyloidoisis, autoimmune disease, cancer and paraneoplastic syndromes and eclampsy. During the exclusion of infective disease, high levels of inflammation indexes (C-reacting protein and Erythrocyte Sedimentation Rate) and low C3 and C4 complement values were detected, these findings together with recent onset of intermittent fever required a more accurate study. Multiple hemoculture tests, drawn during fever peaks, showed a single positivity for S. epidermis, which was assumed as contamination of the blood sample, all other infections specific and unspecific tests resulted negative. Before proceeding with invasive diagnostic method as a renal biopsy to exclude a primitive disease cause, a review of international literature was made considering peculiar characteristics of our patient (ventriculo-atrial shunt carrier). Several case reports and reviews on ‘‘Shunt Nephritis’’ came to our attention since clinical symptoms, laboratory results and disease natural history were almost super imposable. Shunt nephritis is an immune-complex mediate glomerulo-nephritis associated with chronically infected ventriculo atrial shunts inserted for treatment of hydrocephalus. In device carrier patients a single hemoculture for S. epidermis could be considered diagnostic for infection. Before starting an antibiotic treatment (meropenem and linezolid), a culture of cerebro spinal fluid was performed, collected from the transcranial

valve of the shunt system, but with a negative outcome for bacterial growth. This findings seemed to direct the diagnosis away from the shunt nephritis, but from the patient’s history we noticed that during the multiple shunt replacements a portion of an old shunt was left in the left jugular vein. Since strong evidence given from international literature and the few clinical evidence of other causes, except for primitive nephritis, and since the possibility of a surgical approach to the remnant, we decide to remove the infected device, which is considered the only treatment, combined with antibiotic therapy, available for shunt nephritis. After the patient underwent to surgery, a clinical and laboratory improvement was observed in a period of about one week until complete recovery was achieved. Moreover cough that afflicted the patient for all previous years disappeared. Culture of the removed shunt has not been possible for technical problems, but using an ex-adiuvantibus criteria we can say that correct diagnosis was made and appropriate treatment was given.

Profilin desensitization in two patients with plant-derived foods allergy A. Aruanno, E. Nucera, A. Buonomo, T. De Pasquale, V. Pecora, A. Colagiovanni, V. Sabato, A. Rizzi, L. Pascolini, A.G. Ricci, A. Di Rienzo, S. Mezzacappa, M.T. Liuzzo, D. Schiavino Allergy Unit, Universita` Cattolica del Sacro Cuore, Policlinico ‘‘A. Gemelli’’, Rome, Italy We describe the case of two plant-derived food allergic patients, a 36 (patient 1) and a 46 (patient 2) year-old woman, with oral allergic syndrome (OAS), urticaria and gastrointestinal disorders after eating some fruits and vegetables. Patient 1, with rhinitis from January to June, referred oropharyngeal itching, lip oedema, urticaria and sometimes dyspepsia after eating peach, apricot, tomato, potato, eggplant, peppers, melon, avocado, pineapple, lettuce and peanut. Patient 2, with history of rhinoconjunctivitis from March to June, presented urticaria, epigastralgia and abdominal distension after the ingestion of apple, apricot, potato, tomato, eggplant, pineapple, kiwi, watermelon, melon, lettuce, corn, wheat, carrot, banana, chestnut, walnut and hazelnut. Skin prick tests (SPT) to pollens (grass pollen, parietaria, olive tree, cypress, mugwort, birch, beech tree, hazel tree) and some plantderived foods (apple, peach, tomato, kiwi, hazelnut, peanut, banana, walnut, potato, lettuce, wheat, carrot, etc.) were performed. Moreover, since we suspected cross-reactivity between pollens and food, related to the presence of panallergens, such as profilin, nonlipid transfer protein (nLTP) and PR 10 proteins, we also tested patients for these allergens with SPT (Alk-Abello`, Milan, Italy) and specific IgE assay (UniCAP, Phadia, Uppsala, Sweden). Patient 1 had positive SPT and specific IgE to grass, birch tree, profilin and to all the vegetables referred in clinical history (profilin specific IgE: 13 kU/l).

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S192 She underwent double-blind placebo-control challenge (DBPCFC) test with peanut and profilin extract, which resulted positive (oropharyngeal itching, lip oedema and throat-ache, that receded with antihistamines and corticosteroids endovenous therapy). DBPCFCs with other culprit food were not performed because the patient had recent reactions. Therefore, at the end of the allergological evaluation, we made the diagnosis of allergic rhinitis (grass and birch pollen) and food allergy determined by a profilin cross-reactivity. We thus attempted to treat the food allergy and the woman underwent a sublingual desensitization treatment with profilin extract in 13 months without side effects. At the end of the treatment the patient underwent DBPCFCs with peanuts and tomatoes and, in order to evaluate the immunological changes occurring during the immunotherapy, we performed the detection in serum of specific IgE to profilin and indicted food. Challenges were negative for both, peanuts and tomatoes, and the patient showed a decrease of specific IgE levels for profilin and vegetable food, but didn’t reach normal values. Patient 2 had positive SPT and specific IgE to spring pollens (parietaria, grass and olive tree), profilin (14.9 kU/l) and also to every plant-derived food referred in anamnesis. She underwent DBPCFC only with profilin, because she had recent adverse reaction with several vegetables and fruits; the test resulted positive (cough and oral itching) and the patient treated with aerosol therapy (salbutamol and beclometasone). Therefore, patient 2 underwent the same sublingual desensitization treatment in 10 months without side effects. At the end of the treatment she underwent DBPCFCs with kiwi and tomato, that resulted negative, and her profilin specific IgE showed a significant decrease (2.52 kU/l). In this case report, we tried to evaluate the effectiveness of profilin desensitization in patients with allergy to vegetables and fruits crossreacting to this proteins. At the end of the treatment both patients showed tolerance to several foods that previously did not tolerate.

A case report of pyoderma gangrenosum malignant associated with IBD: therapeutic perspectives A. Cappelli1, P. Sperti1, A. Onesti1, V. Verardi2, R. Barbati3, R. Temperilli1 UOC II Medicina; 2U.O.C. A.S. Centro Grandi Ustionati e Chirurgia Plastica; 3UO Dermatologia, Ospedale S. Eugenio, ASL RMC Roma, Italy 1

We report the clinical case of a woman 51 years old from Sri Lanka suffering from ulcerative colitis in clinical remission and with a history of previous PG in clinical remission for several months until the time of our clinical observation. The patient was admitted for recurrence of PG with polymorphous skin lesions characterized by vesicles, dermo hypodermitis and eschar sited at the right breast. Despite the early treatment with systemic steroids at high dosage and with aziathioprine in few days the disease worsened progressively and aggressively for the appearance of new lesions in multiple sites (face, trunk, upper and lower limbs). Some lesions progressed to skin necrosis causing sepsis complicated by DIC. The PG is a neutrophilic, ulcerative dermatosis, accompanied by mucopurulent or hemorrhagic exudate, associated in 70% of cases with underlying systemic disease (IBD, malignancy, rheumatological or emathological disease). In the pathogenesis of PG the neutrophilic component is important. In this case we can speak of malignant pyoderma as this severe recurrence was not associated with a recurrence of the underlying

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 disease; to the extent and aggressiveness of skin lesions involving the lower limbs to the gangrenous mummification of the fingers. The treatment of PG is empirical, based on the use also concurrent of immunosuppressive and immunomodulatory agents (corticosteroids; cyclosporine; azathioprine; mycophenolate, ecc) and local topical wound-care. The TNF alfa stimulates the synthesis of G-CSF, neutrophil activation and release of pro-inflammatory cytokines. Pharmacologic inhibition of the pro-inflammatory cytokine TNFalfa has demonstrated efficacy for a wide range of inflammatory conditions, including IBD e PG. In our case where there is a severe disease with poor prognosis in the fifteenth day from the beginning of our clinical observation we began treatment with adalimumab a fully human monoclonal antibody to TNF-alfa. In the eighth week the patient underwent surgery with removal of large areas of necrotic skin tissue and homologous skin transplant. The clinical follow up in the coming months will allow us to assess the effectiveness and appropriateness of the use of adalimumab and skin grafting in the malignant PG.

A refractory adult onset Still’s disease V. Caterino, R. Esposito, V. Coletta, D. Scognamiglio, G. Amore, C. Cimini, A. Izzo, R. Giunta V Divisione Di Medicina Interna e Immunoallergologia, SUN, Naples, Italy A 68-year-old man was admitted to our hospital on October 2009 because of fever, polyarthritis and sore throat. He had been well until approximately 3 week earlier, when he developed fever and sore throat and an evanescent skin rash on the trunk, followed by polyarthralgia. Until 1 week before admission, he had received antibiotics (ceftriaxone and piperacillin), but had shown no response. He had a quotidian fever with spike C 39C in the afternoon, followed by defervescence with drenching sweats. On admission, he had fever (39C), polyarthritis (bilateral knees, metacarpophalangeal and metatarso-phalangeal joints), generalized myalgias and a salmon pink rash on the trunk. The patient denied any pharmacologic therapy; his medical history was negative. He did not smoke or drink alcohol. Initial blood data showed a neutrophilic leukocytosis (12.800/ml, neutrophils 9.800/ml), hemoglobin 12,8 g/dl, platelets 120.000/ml, erythrocyte sedimentation rate 100 mm/h, Creactive protein 26 mg/dl. Laboratory tests including liver and kidney functions, electrolytes, glucose, cholesterol, LDH, triglycerides, creatine kinase, uric acid, b2 microglobulin were normal. Serum ferritin levels were high (3.000 ng/ml). Rheumatoid factor and antinuclear antibody were negative. Blood and urine culture were sterile. Serological tests for EpsteinBarr virus and anti-cytomegalovirus IgM antibodies and a skin test for tuberculosis showed negative results. A computed tomography (CT) scan was negative for neoplasia. A diagnosis of Still’s disease was made and steroid therapy was started at a daily dose of 75 mg (1 mg/kg) with oral Methylprednisolone. After a transient improvement, a mild reduction of the dose of Methylprednisolone caused a relapse of the disease. To avoid prolonged high-dose steroid therapy, the patient had been successfully maintained on a dose of 25 mg of Methylprednisolone and 200 mg of oral Cyclosporin A. On February 2010 a relapse of the disease occurred with arthritis of both elbow and high fever ([ 39C). For this reason, a biological therapy was started with Infliximab (5 mg/kg on weeks 0, 2 and 6, continuing with intervals of 8 weeks), associated with Methotrexate(15 mg i.m. every week) plus folic acid.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Six months later he developed a deep asthenia. His blood examination showed a macrocytic anaemia(Hb: 7,3 g/dl; MCV: 100,8 fl; MCH: 35,9 pg) and thrombocytopenia (PLT 80.000/ml). Bone marrow aspiration showed a myelodysplastic syndrome, which can often be associated with Still’ s disease. A positron emission tomography/CT scan indicated 18 F-fluorodeoxyglucose uptake in the bone marrow. Because of unfavourable response to Infliximab, we decided to began treatment with Anakinra at 100 mg/day. He required continuous multiple blood transfusions and after four months, a high fever occurred with new salmon pink skin rash on the upper and the lower limbs. So, the patient switched his treatment on Tocilizumab 8 mg/kg with intervals of 4 week: after ten days our patient died suddenly, likely for myocardial infarction. Still’s disease is a systemic inflammatory disorder of unknown etiology. The inflammatory cytokines, including IL-6, IL-18, IFNc and TNF, play pathogenic roles in the disease processes of Still’s disease. Epidemiological studies have established that rheumatoid arthritis and Still’s disease are associated with an increased risk of cardiovascular disease. This heightened risk is not completely attributable to traditional CV risk factors and there is growing evidence that inflammatory mediators contribute to the risk. Moreover, recent studies indicate that inflammation plays a key role in atherosclerosis among patients without an underlying inflammatory disease. Inhibiting inflammatory cytokine may be a sensible therapeutic strategy for Still’ s disease. On the other hand, it is unknown whether the blockade of a single cytokine pathway in the setting of a cytokine storm, if any, causes an unfavorable imbalance in the cytokine system or whether it is sufficient to suppress the inflammatory condition. An unfavorable imbalance in the cytokine could increase the risk of the cardiovascular disease. Our patient hadn’t any cardiovasculary risk factor and also if we suppose there are correlation between his myocardial infarction and Still disease, we can’t exclude the correlation between biological therapy and sudden death.

Acquired hemophilia A in an elderly patient at high thromboembolic risk: a case report A.M. Cerbone, A. Guida, A. Tufano, P. Conca, P. Ierano`, E. Marrone, A. Nardo, E. Cimino, A. Coppola, G. Di Minno Department of Clinical and Experimental Medicine, University ‘‘Federico II’’ of Naples, Italy A 77 years old male patient presenting haematuria, anemia and muscle haematomas was admitted to our regional reference centre for coagulation disease for a prolonged APTT (72’’), non corrected from mixing test. Coagulation tests were performed revealing FVIII: C = 0.90% (70-120%), FVIII:C Inhibitor 13 Bethesda units (BU) and acquired Haemophilia A (AHA) was diagnosed. For this reason oral corticosteroids (prednisone 1 mg/kg per day) and cyclophosphamide (1.5 mg/kg daily) were started, as currently recommended. He had a history of arterial hypertension, hypercholesterolemia, chronic obstructive pulmonary disease, cigarette smoking, and a recent history of hyperthyroidism. Because of stable haemoglobin levels and cessation of haematuria, bypassing haemostatic agents (such as recombinant FVIIa or APCC) were not administered. In the following days, clinical stability was observed and a progressive shortening of APTT emerged, while persisting a low-titer FVIII inhibitor. Further laboratory tests showed neither autoimmunity, nor infectious disease, and instrumental tests revealed absence of evident neoplasm or deep haematomas (CT scan, PET-CT scan were both negative). At the day 15 the patient presented with atrial fibrillation, lasted more than 24 h,

S193 and an episode of cerebral ischemic attack: for this reason he was treated with propaphenone and beta-blockers, in order to achieve a rate control, and low doses of a low molecular weight heparin (enoxaparin 4000 UI twice daily subcutaneously) were started, despite the haemorrhagic risk due to the underlying acquired hemorrhagic disease. The CNS CT scan revealed an ischemic area in the left putamen. Once obtained the negativization of FVIII:C inhibitor (at the day 30), oral anticoagulant therapy (OAT), INR range 2.0-3.0, was bridged because of a CHADS2 score of 5. The immunosuppressive therapy was progressively reduced after the week 4 and then withdrawn according to the standard protocol. No relapse of AHA during the monthly follow up and laboratory check of FVIII: C inhibitor emerged in the first 6 months. The patient was also attentively monitored as to hemorrhagic complication of the OAT and neither major nor minor haemorrhagic manifestation were observed. We described a case of coexistence of bleeding and thrombotic risk in a rare acquired bleeding disorder.

Attention: it is a BOOP S. Chimienti, A. Marseglia, L. Catalano, S. Antonaci, G. Giannelli Dipartimento di Clinica Medica, Immunologia e Malattie Infettive, Bari We are describing the case of a 70 years old woman, who came to our observation for recurrence of several months of productive cough with purulent sputum, and fever, associated with chest pain intensified by breathing. Her history was absence of disease worthy of note. She presented a chest X-ray image performed a few days before showing multiple and diffuse ipodiaphanous oval formations. During hospitalization blood tests were performed with evidence of mild leukocytosis with a formula preserved; elevated index of inflammation; liver functionality, kidney functionality, electrolytes, LDH, and autoantibodies: in the standard. Also a Total body CT scan was performed with detection of areas of parenchymal consolidation round and confluent, some empty and other surrounded by groundglass parenchymal hyperdensity at lower lung lobes. This framework is compatible with aspergillosis and tuberculosis. The patient underwent a bronchoscopy and Mantoux tests both resulting negative. Aspergillus antigen research was performed in serum resulting positive and has been followed immediately an antimycotic therapy. Chest CT scan performed after 10 days showed a modest increase in the size of the areas of parenchymal consolidation. However, the CT framework was also compatible with BOOP (bronchiolitis obliterans with organizing pneumonia). Therefore, corticosteroid therapy was followed as the criterion ‘‘ex adiuvantibus’’; the CT scan performed after 15 days showed a dramatic improvement of the lung. The idiopathic interstitial pneumonia, BOOP, is characterized by fever, cough and a functional alteration with a restrictive pattern in which the CT frequently shows the consolidation of the airspaces, hyperdensity with areas of ground glass. The disease was resolved after corticosteroid therapy. The patient started a pulmonary follow up. Postmenopausal osteoporosis and atopy F. Ciccarelli, C. Giampietro, G. Sansonetti, M. De Martinis, L. Ginaldi Dipartimento di Medicina Interna e Sanita` Pubblica Universita` degli Studi dell’Aquila, L’Aquila, Italy Post-menopausal osteoporosis is a systemic skeletal disorder characterised by reduced bone mineral density (BMD) and micro

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S194 architectural deterioration of bone tissue resulting in susceptibility to fractures. In the last years several lines of evidence have provided insights into the relationship between bone and immune system, suggesting that osteoporosis could be considered an immunological disorder. This has led to the recent emergence and subsequent rapid evolution of the field of osteoimmunology and to the publication of numerous studies about the risk of onset of osteoporosis in subjects with dysfunctions of the Immune System, such as Rheumatoid Arthritis. However there are only few studies about the relationship between osteoporosis and allergy and their results would seem to be conflicting. The aim of our study was to investigate the relationship between bone resorption and allergy, comparing bone mineral density between allergic and non allergic women. With this purpose we studied 2398 women, attending our Center for Osteoporosis to undergo densitometric assessment. Accurate clinical examination and laboratory tests were performed. Moreover, in those women with a history of atopy, prick test for more common allergens were carried out and total and specific IgE levels were evaluated. Subjects with other diseases causing osteoporosis or treated with drugs inducing bone resorption were excluded. All these data were related with both bone mineral density, evaluated by ultrasonography of heel and confirmed by DXA, and presence of osteoporotic fractures. We therefore compared the values of bone mineral density between allergic and non allergic women. Moreover we separately compared BMD values of allergic and non allergic women both in pre and post menopausal state. Our results showed that the values of T scores of allergic patients were significantly higher than the control group (-1,461 vs -1,729 p \ 0.001). However, considering women in pre and post menopausal state separately, this statistical significance was confirmed only in post menopausal women (-1,489 vs -1,830 p \ 0,0001), whereas no differences were found between bone mineral density of atopic and non atopic premenopausal subjects. These findings evidentiate for the first time that atopy, although doesn’t influence bone mineral density in young women, surprisingly represents a protective factor for the onset of postmenopausal osteoporosis.

Mild bleeding disorders (MBD): laboratory approach M.R. Cozzi, M. Battiston, C. Suine, R. Boschian Boschin, A. Steffan Department of Laboratory Medicine, CRO National Cancer Institute, I.R.C.C.S. Aviano, Italy Objective: In daily practice physicians frequently evaluated patients with bleeding tendency that comprise hematoma, epistaxis, menorrhagia or bleeding episodes after surgery or injuries. The bleeding history may often overlap with that reported by normal people and in these situation there are many questions to evaluate: is it a pathological bleeding? Which part of blood coagulation may be affected primary hemostasis or secondary hemostasis? What should be the best laboratory approach in these patients to identified subjects at risk of major bleeding? The evaluation of MBD have to start from an accurate bleeding history in the propositus and his/her family and from a quantitative assessment of bleeding severity. In this work we consider short screening coagulation test associated at extended laboratory tests, performed in patients referred to our laboratory with diagnosis of MBD, to improve diagnostic efficiency. Methods: This study was conducted from January 2010 to March 2011 on patients scheduled for pathological bleeding tendencies,

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 without any acquired causes. Patients, of all ages and both gender, were grouped according to clinical manifestation: profuse menstruation (6), prolonged bleeding after minor surgery (6), prolonged bleeding after major surgery (6) and cutaneous symptoms (6). To confirm an abnormality of primary hemostasis or coagulation were investigated first stage tests (platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT). The global platelet response were assessed with Platelet Function Analyzer PFA-100 and Platelet Aggregation with ATP release, performed using lumiaggregometer. To evaluate defects of plasmatic coagulation factors were investigated VWF, FVIII and fibrinogen. Patients remain drug free for 10 days prior to testing. Results: Among 24 subjects, a laboratory abnormality in first stage tests were found in 9 subjects (37%): in 5 patients were diagnosed von Willebrand Disease (VWD Type I) and in 4 patients were diagnosed Inherited Platelet Disorder (IPD). Extended laboratory tests identified abnormality in primary haemostasis in another 5 patients (21%): in 4 patients were diagnosed VWD Type I, in 1 patients were diagnosed IPD. Conclusion: Our results indicate that screening laboratory tests (platelet count, aPTT, PT, PFA-100) is not sufficient to identify hemostatic defects in all patients with MBD and additional tests to evaluate global platelet response and defects of plasmatic coagulation factors (VWF) are required. An accurate bleeding history, with quantitative assessment of bleeding severity, associated with secondline tests permit to improve diagnostic efficiency in selected patients.

An unusual case of chronic anemia G. Cristiano, A. D’Alessio, C. Cimini, R. Esposito, G. Amore, R. Giunta, G. Lucivero, P. Esposito V Divisione di Medicina Interna e Immunoallergologia, SUN, Naples, Italy On November 2010, a 77 years-old woman was referred to our department for the appetite loss, malaise, asthenia and mild exertional dyspnea. On medical history arterial hypertension, treated with lisinopril, and mild anemia (Hb 9,8 g/dl) associated with iron deficiency (serum iron 18 g/dl, normal values 55-190 g/dl) for two years. She required continuous oral iron supplementation, then intravenously. Her upper gastrointestinal endoscopy showed antral erosive gastritis with multiple gastric ulcers. She began therapy with proton pump inhibitor and sucralfate, without sustained haemoglobin response or endoscopic improvement of mucosal lesions. On admission, a full blood count showed microcytic hypochromic anemia (Hb 11 g/dl, MCV 74 fL, MCH 25 pg/dl, MCHC 30 g/dl, iron level of 38 g/dl). No gastrointestinal symptoms were referred. She did not smoke or drink alcohol. The patient didn’t the use aspirin, non steroidal anti-inflammatory drugs. On physical examination, the patient was pale. Serum levels of vit. B12 and complement were normal. Laboratory data, liver function test, serum albumin, renal function test and blood platelet count were within normal limits. Prothrombin time and international normalized ratio were normal too. We suspected a Zollinger Ellison Syndrome : gastrin level was above 800 pg/ml. The Octreoscan test was negative for gastrinoma. Therefore her hypergastrinemia was attributed to her antisecretory treatment. A new upper gastrointestinal endoscopy revealed a typical ‘‘watermelon’’ aspect, with multiple longitudinal stripes of red vessels, limited to the gastric antrum and radiating in a spoke-like fashion from the pylorus to the antrum. Biopsy specimens showed dilated blood vessels without obvious thrombosis, slight infiltration of lymphoid cells and fibrosis hyperplasia in mucosa. These findings were

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 concurrent with pathologic features of GAVE (Gastric antral vascular ectasia), which could explain also the anemia. Because of her hands skin were taut, firm and thickened, we began to think that the GAVE of our patient could be just a manifestation of a connective tissue disease. Our suspicion was confirmed by positive antinuclear antibody (ANA 1: 1280) with positive anticentromere and anti- scl70 antibodies. Pulmonary function tests showed a restrictive deficit and low diffusing capacity and low PO2 with exercise. Thoracic high resolution computed tomography showed pulmonary fibrosis. The capillary beds of nail folds of the fingers were disorganizated with dilated capillaries interspersed with areas where capillaries have disappeared. On December 2010, we made diagnosis of classical systemic sclerosis with lung involvement; so the patient begun monthly therapy with intravenous Methylprednisolone (1000 mg) and Cyclophosphamide (750 mg/m2), with Mesna as a urothelial protective agent. Both scleroderma and anemia improved and our patient maintained a haemoglobin level higher than 12 g/dl after four months of immunosuppressive therapy and no longer required intravenous iron supplementation. Now our patient is going on with the Cyclophosphamide treatment. GAVE has been increasingly recognized as an important origin of GI tract bleeding, even if it is most often misinterpreted as antral gastritis by endoscopists as in our patient. GAVE is associated with several other clinical conditions (liver cirrhosis, chronic renal failure, diabetis mellitus and bone marrow transplantation), but especially with autoimmune diseases as systemic sclerosis, hypothyroidism, primary biliary cirrhosis, and Sjogren’s Syndrome. The treatment of GAVE is usually endoscopic with argon plasma coagulation. A significant number of patients proceed to the partial gastrectomy. H2 histamine antagonists, tranexamic acid and oestrogen-progesterone preparations have been used as non-surgical treatments for GAVE, with poor success. Cyclophosphamide and methylprednisolone were given to our patient in view of her lung and skin disease, but there was also a complete stabilization of haemoglobin and partial resolution of endoscopic abnormalities. If autoimmune mediated gastric mucosal damage is a significant factor in the development of GAVE, partial resolution may be expected on immunosuppression. According to some authors GAVE, when associated with SSc, is a manifestation of SSc microangiopathy and accompanying vascular changes are caused by activation of inflammatory cells, leading to endothelial cell damage, cytokine release and further vascular damage. There is a significative improvement of SSc- associated GAVE after treatment with Cyclophosphamide. So, there may be a role for immunosuppression in patients with GAVE who don’ t respond to conventional treatments.

Saturday night fever A. D’Alessio, G. Cristiano, C. Cimini, V. Caterino, V. Coletta, M.G. Monsurro`, R. Giunta, G. Lucivero V Divisione di Medicina Interna e Immunoallergologia, SUN, Naples, Italy On Saturday night, a 49-year-old woman was admitted to the Emergency Department with continuous fever (40C), sore throat, nausea, epigastric pain and odynophagia lasting 3 days. Physical examination revealed hyperemic oropharyngeal mucosa, mild and no painful cervical lymphadenopathy.

S195 Blood data revealed white blood cells (WBC) at 600/mm3, neutrophils at 6% (40/mm3), and lymphocytes at 82%. RBC, haemoglobin and platelets values were normal. Three weeks earlier, the patient’s WBC count was 6,200/mm3 and her neutrophils were 71%. Biochemical tests (GOT, GPT, albumin, creatinine, bilirubin, PT-PTT, etc.) were normal. The CRP level was 6.1 mg/dl (normal value: \ 0.5). No evidence of viral infections (CMV, EBV, Parvovirus B19, etc.) was found. She received recent diagnosis of hyperthyroidism, for which she began methimazole 10 mg 2 months earlier. Her thyroid function showed thyroid stimulating hormone of \ 0.003 microU/mL, tri-iodothyronine (T3) at 15.2 pg/mL, and free thyroxine (T4) at 65.4 pg/mL. The autoimmune thyroid antibodies were negative for thyrotropin receptors, whereas Ab anti microsome were173 UI/ml (vn \ 30). Also TSH receptor antibody (TRAb) were present. During recovery on Internal Medicine Department, urine culture, throat swab, and 3 blood cultures were performed but they yielded no organism. Chest X-ray was normal. We suspected febrile neutropenia induced by methimazole. Methimazole was discontinued and she started recombinant human granulocyte colony stimulating factor (rHhug-CSF) lenograstim at 150 mg/m2/d, as well as intravenous levofloxacin 500 mg/die, piperacillin/tazobactam 4,5 g 9 3/die and fluconazole 200 mg/die. By the third day, the patient became afebrile and asymptomatic, and her WBC was 7,100/mm3 with neutrophils at 33% (2.300/mm3). Thyroyd ultrasound revealed diffuse thyroid enlargement with hypoechoic pattern and hypervasculariy. A subsequent thyroid scan showed that the uptake of I-131 had increased. So I-131 therapy, 5 mCi, was then provided. Methimazole has adverse hematological effects, ranging from mild leukopenia to agranulocytosis and aplastic anemia. Mild leukopenia, defined as a total white blood cell count \ 4,000/lL, is noted in about 12% of adults and 25%. It is usually transient and does not usually increase the risk of infection and it is not necessary to stop treatment with antithyroid drugs. Agranulocytosis is defined by a decrease in peripheral neutrophil count to less than 500 cells/mm3 and occurs in only 0.3% of patients. Its incidence is 0.55% with propylthiouracil use and 0.31% with methimazole use. Antithyroid drug-induced agranulocytosis occurs most frequently during the first ten weeks of treatment, but it can occur after long-term treatment. There has not yet been any conclusive evidence that the prevalence of agranulocytosis induced by ATDs is dose related. Between 18% and 78% of patients are asymptomatic at the time of diagnosis of agranulocytosis on routine WBC count monitoring. For this reason, some recommend routine WBC monitoring. When neutropenia (WBC 1,500/mm3) is found, then antithyroid drug therapy should be discontinued. Others instruct the patients to stop the medication whenever they develop symptoms of agranulocytosis (e.g, pharyngitis, fever, mouth ulcers, and sore throat) that last longer than 1 to 2 days. The onset of agranulocytosis is abrupt and idiosyncratic. Methimazole possibly induces reversible agranulocytosis through direct toxic effects and immunological reactions. The direct toxic effects affect both mature circulating neutrophils and stem cells. The immunological reactions are IgE-mediated (hypersensitivity reaction) and overall complementdependent (through opsonization by IgM antibodies drug-induced and neutrophil-drug complex). Treatment includes rhG-CSF and broadspectrum antibiotics. In one study, G-CSF shortened the recovery time of agranulocytosis from approximately 10.1 to 12.3 days to 6.8 days. This therapy reduces also the rate of complications from infection and the mortality rate, even in patients with asymptomatic agranulocytosis. G-CSF is mostly effective in patients whose bone marrow granulocyte to erythrocyte ratio is more than or equal to 0.5. Steroids do not seem to shorten the recovery time of neutrophils. The mortality rate is greater in elderly patients. After recovery from agranulocytosis, it is not recommended prescribing antithyroid drugs again, even another type of thioamide, because of common crossreactions among these drugs. Radioiodinetherapy or surgery are better

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S196 choices. Our case had good prognosis after granulocyte colonystimulating factor and empirical antibiotic therapy. The patient had a recovery time of 6 days. In summary, even though methimazole-induced agranulocytosis is rare, physicians should warn patients of agranulocytosis symptoms while taking antithyroid drugs, so they may contribute to an early diagnosis. Whenever patients develop these symptoms, it is important to stop the drug immediately and check a WBC count to avoid a potentially fatal febrile neutropenia. Granulocyte colony-stimulating factor therapy to patients results in good prognosis. Drug-induced agranulocytosis is believed to be an extremely rare adverse drug reaction. It can be caused by various drugs, but it is mostly described in patients taking antithyroid drugs, antipsychotics and antibiotic. Antithyroid drugs (ATDs) are widely used to treat hyperthyroidism, especially Graves’ disease, despite their acceptability, they are associated with many complications, which increases the mortality rate. Agranulocytosis, although rare, is the most severe and life-threatening complication.

Transjugular intrahepatic portosystemic shunt (TIPS) as first approach to haemorrhoidal varices in severe portal hypertension A. De Vincentis, G. Galati, U. Vespasiani Gentilucci, C. Mazzarelli, P. Gallo, V. Ripetti, Rf. Grasso, G. Luppi, E. Faiella, A. Picardi Campus Bio-Medico di Roma, Roma, Italy Case report: A 45-years-old man, known to have an alcoholic Child B liver cirrhosis, was admitted to our clinic for severe anemization (hemoglobin 5,8 g/dL) secondary to persistent rectorrhagia. The patient reported persistent loss of bright blood with stools from a couple of months and he complained about asthenia, dyspnoea and dizziness. On admission he was hemodynamically stable and physical examination evidenced pale skin, tachycardia, tachypnoea and a firm, nontender liver edge 5 cm below the right costal margin with splenomegaly and cutaneous spider nevi in absence of lower limb oedema and clinically evident ascites. Laboratory results showed microcytic anemia and severe thrombocytopenia (46.000/uL), mild elevation of hepatic tests (AST 60 U/L, ALT 43 U/L, GGT 67 U/L, ALP 186 U/L) with normal bilirubinemia and coagulation tests and hypoalbuminemia (2,4 g/dL). We performed a pancolonscopy that evidenced second-degree hemorrhoids excluding other colonic bleeding lesions, while upper endoscopy was negative for varices. A color Doppler US scan of the portal system showed an hepatopetal flow with reduced mean velocity (13 cm/sec) in absence of thrombosis and increased diameter of the portal and splenic vein with partial recanalization of the umbilical vein. An abdominal CT scan with contrast medium detected a patent ectasic superior mesenteric vein with congestion of the rectal venous plexus and confirmed mild perihepatic ascites and splenomegaly. Three units of packed red blood cell and endovenous martial infusion were given to raise hemoglobin and propranolol in growing dosage was started to reduce portal hypertension. In spite of this approach, severe rectorrhagia continued. On anamnestic deepening, 15 years earlier he had undergone an haemorrhoidal prolapsectomy with Longo’s technique and 6 years earlier an haemorrhoidal ligature had been performed because of persistent symptomatic bleeding hemorrhoids. Moreover he referred severe alcohol consumption since he was twenty years old and he had been in relative good conditions since 6 months before, when he had been admitted to our hospital with tense ascites and diagnosis of liver cirrhosis was made. In that circumstance diuretic therapy was started and ascites improved.

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Diagnosis and decision making: Persistent haemorrhoidal bleeding was assessed as the leading cause of anemia and symptomatic haemorrhoidal varices were diagnosed. Although commonly detectable in patients with cirrhosis, haemorrhoidal varices only infrequently cause significant rectorrhagia. Despite there is no standardized approach, it is generally accepted that their management should be directed to ameliorate portal hypertension as they are caused or exacerbate by splanchnic venous congestion. Otherwise surgical risk in cirrhotic patients is significantly higher, so surgeons often decline surgical indication before an optimization of the patient’s general conditions. In this context the transjugular intrahepatic portosystemic shunt (TIPS) was believed to reduce this risk. Treatment: Considering the inefficacy of b-blocker, a TIPS was performed by means of a porto-systemic shunt between the right supra-hepatic vein and the left trunk of the portal vein. The initial portal venous pressure was 22 mmHg and the estimated gradient decreased from 18 mmHg to 4 mmHg after TIPS. This led to haemorrhoidal varices decrease, but rectorrhagia continued and the only solution, thus, was surgical intervention. A transanal haemorrhoidal dearterialisation was performed through a dedicated proctoscope that incorporates a Doppler probe and allows to identify haemorrhoidal arteries and to ligate them, thereby reducing the blood congestion. The surgical approach was successful and rectorrhagia definitively stopped. Discussion: Even though TIPS was realized with success in several reports of rectal varices related to cirrhotic portal hypertension, we suggest that TIPS could be performed as first approach in these cases, in order to reduce degree of portal hypertension and to plan, in case of ineffective fall in rectal congestion, a surgical intervention with a reduced operative risk related above all to a severe bleeding. Reference 1. Kochar et al. Bleeding ectopic varices in cirrhosis: the role of transjugular intrahepatic portosystemic stent shunts. Aliment Pharmacol Ther. 2008;28(3):294-303

Montelukast and Churg-Strauss syndrome. A case report G. Esposito, M.V. Guerra, R. Terribile, P. Onorato, G. Zito, C. Romano, R. Giunta, G. Lucivero V Divisione di Medicina Interna e Immunoallergologia della Seconda Universita` degli Studi di Napoli, Napoli, Italy On February 2011 a 56 year old woman suffering from continuousremittent fever (max 39.5 C), dyspnea, cough, fatigue, abdominal pain, itching palpable purpura and dysesthesias to lower limbs came to our observation. Similar episodes were presented during the last year, regressed with short courses of oral steroid therapy. In her long history of atopic asthma well controlled with inhaled steroids and b2 agonists, until about two years ago when the specialist introduced montelukast (4 mg/die) without further modification therapy. On physical examination: diffuse ronchi and wheezes, palpable purpura from the knee to the foot of both legs, livedo reticularis on posterior region of the right thigh. Laboratory findings pointed out a white blood cell count of 27.5 9 103 mm3 with 19.2 9 103 mm3 eosinophils (69.5%), while the other cell lines and in particular the platelets were normal. Other haematochemical tests showed moderate increase of cholestasis indices (ALP 157U/l, cGT 67U/l) with normal transaminases, and increase of inflammatory markers (CRP 5.20 mg/dl, ESR 78, LDH 776 U/l, hyperfibrinogenemia, ipera1 and a2, hyperferritinemia), Hyper-IgE (848 kU/l) with any specificity.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392

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The immunological study showed negative ANA and ENA, rheumatoid factor significantly high (414.7 umol/l), modest increase in anti-PR3 (21 AU/ml with normal value \ 20), normal limphocities populations. Negative for viral hepatitis markers for current and previous infections, serum cryoglobulins are undetectable; therefore we could exclude cryoglobulinemic purpura. Chest X-ray showed diffuse interstitial commitment, confirmed by HRCT which also showed bilateral medium basal infiltrates. Electromyography revealed an acute neuropathy involving tibial nerve surface. Echocardiogram was normal. Suspecting Churg-Strauss syndrome associated with montelukast, we suspended this drug and performed a skin biopsy on left leg’s region affected by petechial lesions; the subsequent histological examination showed perivascular inflammatory infiltrates, pravalenza constituted by eosinophils. The high number of eosinophils required an evaluation for chronic myeloproliferative syndrome and eosinophilic leukemia: the research on peripheral blood cells for BCR/ABL and FLIP1L1/PDGFRa rearrangements and for V617 Jak-2 mutation were negative. The presence of four of these six criteria of the American College of Rheumatology led us to diagnosis of associated montelukast ChurgStrauss in patients with hypereosinophilic syndrome. Despite the suspension of montelukast, a good control of asthma and vasculitis events weren’t obtained, for this reason we started steroid therapy (prednisone 1 mg/kg/die) resulting a complete remission of itching palpable purpura, a reduction of eosinophilia (800 mm3), of inflammatory markers (CRP 0.20 mg/dl), of cholestasis indices (ALP 40 U/l, cGT 7U/l) and a good asthma control in just 15 days. Conclusions: There are several case-reports of an association between treatment with antileukotriene receptor antagonists and development of Churg-Strauss syndrome, but the pathogenic mechanisms that sustain this association are not completely understood. The most accepted hypothesis is that the interruption/tapering of oral and inhaled steroids could unmask latent vasculite. However, the finding of similar cases in patients who hadn’t previously used oral steroids or didn’t change the dose of inhaled ones (this is our case), suggests other pathogenic hypothesis like the ‘hyperactivity of the leukotriene LTB4, an important eosinophil and neutrophil chemotactic factor, whose receptor isn’t blocked by these drugs. This process could create a state of hypereosinophilia that would support the vasculitis.

pharmacologically treated with hypnotic drugs and atypical antipsychotics (quetiapin, risperidon) without any benefit. Because of the persistence of cognitive and sleep disorders, the patient turned to us. Patient was evaluated with a multidimensional cognitive test of first level, that showed a cognitive impairment, especially in time orientation, in attention and calculation and in registration recall (MMSE 20.8/30). Patient showed also some dependences in basic life activities (ADL 3/6) and in some instrumental activities (IADL 2/5). Important neuropsychiatric alterations came out, such as frequent episodes of hallucinations, agitation, aggression, anxiety and motor disturbance, especially during the night (NPI 39/144). The evaluation of walking and balance highlighted an inappropriate trunk control, dysmetria and a slight postural instability (Tinetti scale 11/28). An encephalic RM highlighted areas of patchy signal in temporaloccipital region, due to focal ischemic lesions in subacute phase or in resolution and multiple areas of cortical atrophy. Based on these data and considering the failure of previous pharmacological treatments, the patient was submitted to a therapy with haloperidol at a dose of V gtt/die. Typical antypsychotics can result useful in such situations because they stop D2 receptor of dopamine and can also act on other systems, such as serotoninergic, cholinergic and anticholinergic, bringing to an effective control of positive symptoms linked to dementia, in contrast with atypical antipsychotics that, acting on D4 receptor of dopamine, are more useful in the control of negative symptoms. At the following control, after a month of treatment, we observed a slight improvement of sleep disorders. At that time, we decided to increase the dose of haloperidol to X gtt/die. At the second control, three months later, we registered a significative regression of sleep disorders with a better cognitive performance (MMSE 22/30; NPI 16/144).Sleep disorders are one of the major complications related to dementia and cause significant impacts on functionality and quality of life in elderly patients. These sleep disorders often contribute to institutionalization so it’s important to control them. The origin of sleep disorders in dementia is usually multifactorial, resulting from pathophysiological changes associated with the disease itself, sensory deprivations. This case proves how, even if use of haloperidol is not encouraged by guide lines as first-line treatment in long term therapies because of its side effects especially at extrapiramidal level, it can however be used, with good results and under close surveillance, in the management of behaviour disorders associated with dementia.

Utility of haloperidol in sleep disorders related to cognitive impairment

The wide spectrum of the granulomatous diseases

E. Ettorre, E. Cerra, F. Colella, C. Fiorucci, M.L. Pontecorvo, M.T. Vigliotta, V. Marigliano

L. Ferri, M. Iannotta, A. Koverech, A. Negro, L. Mattei, G. De Lucia, C. Festa, M. Proietta, M. Trappolini, F. Del Porto

Dipartimento di Scienze Cardiovascolari, Respiratorie, Nefrologiche e Geriatriche Universita` Sapienza Roma, Roma, Italy

Universita` ‘‘Sapienza’’ Roma, Ospedale Sant’Andrea, II Facolta` di Medicina e Psicologia, Dipartimento di Scienze Cliniche e Molecolari, Roma, Italy

We report the clinical case of a 89-year-old-man affected by a prostate carcinoma, treated with chemotherapy and radiotherapy, multifocal leukoencephalopathy, FAC, carotid atheromas, depressure, osteoporosis and osteoarthritis. The patient came to our attention in our outpatients’ clinic, because of a sintomatology characterized by somnambulism, mnesic gaps and verbal aggression. In particular, caregiver related that patient often experienced anxiety while sleeping, episodes of somnambulism with amnesia of what happened once he woke up, and daylight sleepness with a negativistic behaviour. Somnambulism is a parasomnia and, according to DSM criteria, it can be diagnosed when the sleep disorder constitutes the major complaint and it is so serious to require an independent clinical attention. The patient had already been followed in another hospital and

Case report: a 25-year-old man was admitted to our Department because of fever (38.5C), cough and malaise that persisted despite he was taking antibiotic therapy with amoxicillin-clavulanate. The patient reported that the current symptoms were started three months before when appeared a symmetrical and additive polyarthritis first localized to the large joints of the lower limbs and later involving also the large and small joints of the upper limbs. His past medical history was unremarkable. Physical examination showed conjuntival redness and symmetrical arthritis of the ankles. Moreover an abolition of the murmur was documented at the right lower lobe. Laboratory tests showed a slight normochromic normocytic anemia with increased C reactive protein (C-RP 13 mg/dl) and erythrocyte sedimentation rate (ESR 56 mm/h) values. Moreover positive rheumatoid factor (81 mg/dl)

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S198 was observed. Chest X-ray documented the presence of a parenchymal consolidation in the right lower lobe (rounded atelectasias?). Greater density of the right lung ilium because of the possible presence of enlarged lymphnodes. To better clarify the nature of the lesion a total body CT scan was performed showing: Chest. the presence of rare nodules not exceeding one centimeter in the lower lobes, middle lobe and apical segment of right upper lobe is confirmed; in the lateral segment of right lower lobe there is a round large parenchymal consolidation of about 3.5 cm, with air bronchogram in context. Coexist areas of ground-glass opacities predominantly in the upper lobes. Conglomerate adenopathy, not the average diameter of 1.5 cm, in the hilum bilaterally, in aorto pulmonary window and in the right lower paratracheal space. Absence of pleural and pericardial effusion. Abdomen:… centimeter lymph nodes oval shape can be appreciated in the context of the mesenteric adipose tissue. The pulmonary radiological finding directs the diagnosis towards a sarcoidosis. To define the diagnostic possibilities an eye examination was performed and documented an uveitis. Moreover a cutis biopsy on nodules present at the right elbow was done which was consistent with the diagnosis of granuloma annulare. During the hospitalization since an episode of haematuria occurred, the examination of the sediment was done, showing dysmorphic red blood cells with hyaline casts. 24-hour proteinuria was 3.2, thus nephrotic syndrome was diagnosed. On the basis of such permises a systemic autoimmune disease was hypothesized thus an auto-antibodies screening was performed confirming positive RF and IgM anticardiolipin antibodies with negative ANA, anti cyclic citrullinate peptide, ENA. The possible diagnosis were: sarcoidosis (lung involvement, adenopathy, uveitis, polyarthritis, kidney involvment) and extrarticular localization of rheumatoid arthritis (symmetrical and additive polyarthritis, positive rheumatoid factor, evidence of rheumatoid nodules, uveitis, lung and kidney involvement), despite the symptoms were less consistent with the succeeding diagnostic hypothesis extrarticular manifestation of HLA-B27 associated spondiloarthritis (large joints involvement, uveitis, lung and kidney impairment) and a small vessels vasculitis (pulmonary and kidney involvement) were suspected. With the aim to confirm such diagnostic hypothesis HLA B27 and ANCA were measured showing positive cANCA confirmed by EIA at the titre of 43.81 U/ml.

Emergency treatment in fronto orbito zigomatic trauma G. Fini, L. Frontero, E. Mici, V. Pellacchia, A. Leonardi, F. Cascino, M. Carini Dipartimento Nesmos, Facolta` di Medicina e Psicologia, Universita` degli Studi di Roma, Roma, Italy The fronto-orbito-zygomatic regiones is frequently involved in the facial trauma and often is associated with eyelid involvement. From 2001 to 2008 occurred at our centre 135 patients with frontoorbital trauma; patients were included in clinical follow-up until 2010. Most patients (80%) came to our observation in a state of emergency due to automobile accidents, sports injuries or assaults, while a smaller proportion (20%) was as a result of previous trauma or surgery. Among urgent patients, 28 cases present bone lesions without soft tissue involvement, 62 present bone lesions with soft tissue involvement, and 16 present only soft tissue lesions. The maxillofacial surgeon does not participate to the first aid at the scene of trauma but is called immediately after hearing the management of the patient hospitalized. In these patients the maxilla facial emergency treatment provided for the management of the airway, bleeding, compressive

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 optic neuropathy, the imprisonment of the oculomotor muscles and nerve damage. Soft tissue treatment was more difficult and especially eyelid one. Eyelid must be treated as soon as possible to avoid corneal lesions and major complications like total virus lost. Surgical design must satisfy even aesthetic profile in order to guarantee functional success and aesthetic too.

Cardiovascular screening in young athletes: a comparison between different exercise tests for arrhythmia and structural heart defects detection A. Gasperetti, A. Ermolao, M. Zaccaria Sports Medicine Unit, Department of Medical and Surgical Sciences, University of Padova, Padova, Italy Background: In 1982 a pre-participation screening of athletes was launched in Italy. For younger athletes (\ 35y.o.). The protocol included a resting 12-lead ECG together with two more ECG recorded during the recovery phase of a submaximal test (Harvard step test, HST). More recently (2006), Veneto Region established the ECG monitoring throughout the Harvard step test. In our Sports Medicine Unit since 1998 we independently decided to use a maximal treadmill test with ECG monitoring for the same screening purposes. Purpose: Aim of this study was to compare the ability of three different exercise test modalities to detect arrhythmias, and whether they were associated with structural heart abnormalities. Methods: 1500 athletes, mean age 14.7 ± 0.6 (range 8-15yo) were evaluated (500 each) in three Sports Medicine Centers differentiating one from each other by three different test modalities: HST without ECG monitoring (HST), HST with ECG monitoring (HSTM), and maximal treadmill test with ECG monitoring (MTT). Before the exercise test, each athlete underwent a history and clinical evaluation, and a resting ECG. Athletes underwent additional echocardiography and 24-hour ECG monitoring when required. Results: the maximal heart rate achieved was 74,7% (HST), 85,6% (HSTM) and 92,1% (MTT) of the maximal predicted. Arrhythmias (VEB and/or SVEB) were observed in 1%, 2,6%, and 8.6% of the subjects for HST, HSTM, and MTT, respectively. Considering only the monitored exercise phase, arrhythmias were recorded in 0,6% of HSTM subjects (23,1% of total arrhythmias) and in 2,4% of MTT subjects (27,9%). The positive predictive value of generic arrhythmias recorded during the MTT for any echocardiographic structural heart abnormality was 0,35, while was 0,6 when both VEB and SVEB were present. Conclusions: Exercise monitoring increased the sensitivity in detecting arrhythmias and structural heart defects respect to the non monitored exercise test. The MTT induced a greater number of arrhythmias, which were associated with cardiac abnormalities (mainly mitral valve prolapse, PFO, aortic and mitral regurgitation) in 35-60% of subjects, depending on the type of arrhythmias. In athletes screening, ECG monitoring during exercise should be considered to improve the sensitivity of the exercise test.

A study on pleiotropic extrascheletric effects of vitamin D: preliminary results N. Gueli, P. Andreozzi, A. Amici, W. Verrusio, A. Linguanti, A. Martinez, R. De Angelis, F. Di Maio, V. Marigliano, M. Cacciafesta Dipartimento di Scienze Cardiovascolari, Respiratorie, Nefrologiche e Geriatriche, Sapienza Universita` di Roma, Roma, Italy

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Introduction: Vitamin D is a pre-hormone which acts via metabolites of which the most active is 1.25(OH)2D or 1.25 dihydroxycholecalciferol or calcitriol; this binds to specific receptors, the vitamin D receptors (VDR), which function as nuclear transcription factors. Besides increasing calcium bowel absorption and promoting the normal formation and mineralization of bone, this vitamin exerts relevant pleiotropic effects in different tissues. Serum levels of vitamin D show correlation with the risk of infections, cardiovascular diseases, cancer, autoimmune and neurological disorders. Numerous reports suggest the mechanisms with which calcitriol has diverse extra-skeletal effects : there are receptors in the encephalon, prostate, breast, colon and in the immune systems cells; these receptors control, directly or indirectly, numerous genes implicated in cellular differentiation and proliferation processes, apoptosis and angiogenesis; cellular proliferation is reduced in both normal and neoplastic cells, inducing differentiation; augment myocardial contractility and insulin synthesis; renin synthesis is inhibited; and immunomodulatory functions are evident. The purpose of our study is to administer vitamin D to a population and observe: its pleiotropic effects and the effectiveness on preventing CV diseases, dismetabolic disorders, disorder of mood, the risk of falls and frailty, the effects of association with physical training. Materials and Methods: We selected 30 subjects with hypovitaminosis D in stable conditions, mean age 67.5 years (± 17.5). We administered an oral dose of 25.000 UI of cholecalciferol twice each month to all subjects and a loading dose only to those with blood levels of 25 OH D \ 20 ng/ml. Each patient was provided with some recommendations for a diet rich in vitamin D. All subjects were evaluated, at the beginning of this study (T0) and at six month from the start (T1), with the Multi Dimensional Geriatric evaluation and Cardio Vascular Risk evaluation, echocardiogram, a Holter monitor and ABPM, lab tests (routine blood tests, calcemia, 25 OH D), osteodensitometry. Results: preliminary results, after six months, confirm the beneficial effects of the supplementation therapy on bone tissue quality and subsequent reduction of osteoporosis risk, on postural stability with maintaining adequate level of self-sufficiency, reducing frailty and fall risks. Our dose of supplementation is safe and free of side effects. Conclusions: The possible therapeutic role of vitamin D in different kind of diseases (inflammatory, immunologic, infectious, neoplastics, neurologicals) explains the growing interest in this vitamin due to its pleiotropics effects. It is our intention to prosecute our study, enlarging studied population and evaluating effects of vitamin D supplementation. Preliminary results add an evidence on which we can state that vitamin D, both for the therapeutic effects of its low cost, should be used more, especially in the elderly at risk of hypovitaminosis.

Plasma neutrophils are increased in overweight/obese patients and are associated with early impairment of cardiac diastolic function C. Marchesi, A.M. Maresca, C. Mongiardi, F. Annoni, L. Merletti, V. Vacirca, E. Nicolini, A. Bertolini, A. Venco, A.M. Grandi Department of Clinical Medicine, University of Insubria, Varese, Italy Background: Experimental findings suggested that neutrophils contribute to left ventricular (LV) remodeling due to volume and pressure overload, through pro-oxidant mediators released in the myocardium. Obesity is associated to increased airway polynuclear cell infiltration, LV remodeling and systemic oxidative stress. Thus, we questioned whether plasma neutrophil levels are increased in overweight/obese patients and correlate with LV remodeling and function.

S199 Methods: We consecutively enrolled patients attending our out-patient clinic for cardiovascular (CV) disease: 40 patients with body mass index (BMI) C 25 kg/m2 and 21 patients with BMI \ 25 kg/m2. All the patients were no smokers, never treated with antihypertensive drugs or statins and without overt CV disease. All patients underwent: echocardiography, ambulatory blood pressure (BP) monitoring and plasma measurement of white cell count. Results: The two groups were similar for mean age, gender, systolic and diastolic BP throughout the 24 h. LV mass, indexed for height powered 2.7 (h)2.7, was normal in all the patients and higher in the overweight/obese ones (37.6 ± 7.2 g/h2.7 vs 30.4 ± 5.8 g/h2.7, P \ 0.0001). Relative wall thickness was not different between groups. With regard to LV diastolic function, overweight/obese patients showed higher left atrial diameter and volume (35.5 ± 2.8 mm vs 33.1 ± 2.9 mm, P \ 0.01 and 46.4 ± 11.3 ml vs 37.5 ± 13.2 ml, P \ 0.01), lower Em/Am (0.73 ± 0.19 vs 0.89 ± 0.32, P \ 0.05) and E’/A’ (1.1 ± 0.4 vs 1.2 ± 0.4, ns) from septal and lateral Tissue Doppler Imaging, and higher E/Em (7.56 ± 1.59 vs 6.26 ± 1.27, P \ 0.01) and E/E’ (4.90 ± 0.91 vs 4.36 ± 1.03, P \ 0.05). Plasma absolute neutrophil count was normal in all the patients, but higher in overweight/obese patients (P \ 0.01), and positively correlated with BMI (r = 0.24, P = 0.06), left atrial diameter (r = 0.26, P \ 0.05) and volume (r = 0.27, P \ 0.05), E/Em (r = 0.35, P \ 0.01) and E/E’ (r = 0.28, P \ 0.05). Conclusions: We found that plasma neutrophil levels are higher in overweight/obese patients and are associated with early impairment of LV diastolic function. Our preliminary results suggest a potential role for plasma neutrophils as markers/mediators of cardiac remodeling in obesity.

A case of sepsis caused by Delftia acidovorans P. Marinelli, M. Internullo, L. Borgognoni, V. Fontana, A. Russo, P. Baiocchi, E. Angelici, P. Palange Sapienza Universita` di Roma, Policlinico Umberto I, Dipartimento di Sanita` Pubblica e Malattie Infettive, UOC Medicina Interna I, Italy A 55 years old woman was admitted to the our department because of fever (39C), mild nausea, vomiting and generalised rash. Patient’s medical history included thymic carcinoma, diagnosed 8 years earlier and treated with six cycles of chemotherapy. On July 2010 Lung and liver metastases were identified (two lung metastases were surgically removed). She also had myasthenia gravis, treated with prednisone and polyclonal intravenous immunoglobulin. A port-a-cath had been implanted in 2010. On admission laboratory findings revealed a neutrophilic leukocytosis (16,840 WBC (neutrophil count 81%) and a moderate anemia with Hb 7.3 g/dl. A chest X-ray showed ‘‘No parenchymal alterations. Elevation of the left hemidiaphragm subsequent to the left lower lobectomy and obliteration of the ipsilateral custophrenic sinus.’’ Given the patient’s severe condition, after blood was obtained at a fever peak for blood cultures empirical antifungal and antibiotic therapy with fluconazole, vancomycin and meropenem was started on the first day. Blood cultures proved positive for Klebsiella pneumoniae and Candida albicans. In this light the Porta-Cath was removed. Candida albicans was isolated from the catheter. A femoral central venous catheter was implanted. Ten days after the CVC removal, thrombosis of femoral vein and pulmonary embolism occurred. Therefore, an inferior vena cava filter was placed. Furthermore, a new Port-a-cath and PICC LUMEN CVC in the right arm were implanted. On the tenth day the temperature rose again to 39 C. The differential diagnosis of a neoplastic patient presenting with nosocomial fever is very broad. In these subjects is caused more

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S200 frequently by infectious disease and less frequently by para-neoplastic and autoimmune disease. Therefore urine culture, blood cultures from peripheral vein and from Port-a-cath were performed. Blood cultures were positive for Delftia acidovorans . Delftia acidovorans (Comamonas acidovorans) is an aerobic, nonfastidious, non-fermentative gramnegative bacillus classified in the Pseudomonas rRNA homology group III. D. acidovorans has been associated with serious infections such as central venous catheterassociated bacteremia. D. acidovorans is still considered a highly unusual pathogen that is rarely isolated from biological specimens. Timely identification of this organism to the species level is necessary to determine the most appropriate antibiotic therapy, because this organism is uncommon and often resistant to a class of drugs commonly used to treat systemic gram-negative infections (1),(2),. Antibiotic treatment with meropenem and teicoplanin, based on antibiogram was started and a labeled leukocytes scintigraphy was performed to localize the site of infection. An inflammatory process in the right inguinal region compatible with an infection at the level of thrombus in the femoral vein was detected. The patient was discharged and will continue antibiotic therapy with levofloxacin and amoxicillin for a total of ten days. The follow up at one month showed the patient in a good clinical state. References 1. Gilligan PH, Lum G, Vandamme P and Whittier S. Burkholderia, Stenotrophomonas, Ralstonia, Brevundimonas, Comamonas, Delftia, Pandoraea, and Acidovorax. 2003 2. In: Murray PR, Baron, EJ, Jorgensen JH, Pfaller MA, Yolken RH, editors. Manual of clinical microbiology. 8th ed. Washington: Am. Soc. Microbiol. pp: 729-48.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Conclusions: In a selected group of CHF patients with coexisting GH deficiency, long-term GH replacement therapy appears safe and effective.

Controls Baseline

GH therapy 2 years

Baseline

2 years

p*

p 

NYHA class

2.6 ± .3

2.5 ± .2

2.5 ± .2

2.2 ± .1

.05

ns

MLHFQ

44 ± 11

41 ± 8

47 ± 4

35 ± 5

.001

.01

119 ± 12

94 ± 9

180 ± 16

.0001 .0001

IGF-1 (ng/ml)

115 ± 11

NT-proBNP (pg/mL)

4600 ± 630 4100 ± 415 5331 ± 950 2840 ± 720 .05

.03

Exercise duration (s)

544 ± 24

578 ± 27

471 ± 33

575 ± 40

.01

.01

Peak VO2 (ml/kg/min)

13.2 ± 1

14.9 ± 1

14.1 ± .2

18.1 ± .9

.004

.01

End-systolic stress (kidneys/cmq)

402 ± 45

410 ± 57

405 ± 40

290 ± 45

.001

.05

Ejection fraction (%)

34 ± 4

35 ± 3

32 ± 3

41 ± 4

.01

.001

Flow mediated vasodilation, %

9.4 ± 1

10.1 ± 2

8.7 ± 1.5

14.5 ± 1.6

.001

.01

Data expressed as mean ± SE; p*; = p vs. baseline; p  = p vs. control group (D change between-group).

When the visceral fat…it’s too little A. Marseglia; S. Chimienti; L. Catalano; S. Antonaci; G. Giannelli Dipartimento di Clinica Medica, Immunologia e Malattie Infettive, Bari, Italy

GH replacement in adults with chronic heart failure. Preliminary long-term results A.M. Marra1, M. Arcopinto1, E. Bobbio1, A. Salzano1, D. Sirico1, D. Celentani1, F. Ferrara1, E. Bossone2, A. Cittadini1, L. Sacca`1 1 Dipartimento Medicina Interna, Scienze Cardiovascolari ed Immunologiche, Universita` di Napoli ‘‘Federico II’’, Naples, Italy; 2 Dipartimento Cardiologia e Cardiochirurgia, Ospedale Universitario ‘‘Scuola Medica Salernitana’’, Salerno, Italy

A reduced activity of the GH/IGF-1 axis (GHD) in chronic heart failure (CHF) has been described by several independent groups, and short-term evaluation of its correction has recently proven to be beneficial. No data are currently available regarding the long-term safety and efficacy of GH replacement therapy in patients with GHD and CHF. Methods and Results: Aim of the current study was to report data obtained from 17 CHF + GHD patients treated with GH replacement therapy and 17 controls followed over a two-year period. All patients included had GHD diagnosed by means of a standard GH stimulation test and were treated with GH replacement therapy on top of standard medical therapy. Results: The main results are summarized in the table below. Patients treated with GH displayed a significant improvement of cardiopulmonary performance, vascular reactivity, and ejection fraction while left ventricular end-systolic stress decreased significantly compared with control CHF patients. Safety was good, considering that only one patients complained of transient arthralgia. Compared with 6-months data (not shown), there was not only a sustained GH effect to improve clinical status and cardiovascular performance, but some parameters such as peak oxygen consumption and flow mediated vasodilation exhibited additional increments at two years.

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We are describing the case of a 27 years old woman, who came to our observation for recurrence of vomiting, widespread abdominal pain and weight loss over 20 kg in the last 30 months, with no reported episodes of diarrhea. She reported a diagnosis of celiac disease in early childhood for which she never followed a glutenfree diet, a long history of dyspepsia, and progressive weight loss after the second pregnancy at age 23. About ten days before our observation she was recovered in Gastroenterology, where she performed an abdominal CT suggestive of intestinal lymphoma. Cervical- lymphnodes are palpated bilaterally. During hospitalization her blood tests and abdomen ultrasound resulted in the standard; antibodies against endomysium, anti-gliadin and antitransglutaminase resulted positive; neck ultrasound demonstrated reactive nodes. She refused endoscopy, but it was performed after being discharged with the histological confirmation of celiac disease. X-ray of the esophagus-stomach-duodenum with barium showed that at the third portion of duodenum a vertical linear defect with extrinsic compression. Abdomen MR confirmed the origin at an acute angle (16) mesenteric artery from the aorta. Wilkie’s syndrome is a rare cause of mechanical obstruction caused by the reduction of visceral adipose tissue in which the third part of the duodenum is compressed between mesenteric artery and aorta, predominantly found in young patients who have presented significant weight loss. Treatment involves: nutritional support and postural therapy in mild cases, or a surgical intervention with duodenal-jejunal anastomosis in serious cases. In our opinion the second pregnancy has been the cause that have sparked celiac disease (as described in the literature), that is been the cause of excessive weight loss, responsible of vascular topographical rearrangement that, as a loop, led ultimately to the Wilkie’s syndrome. The patient was then a candidate for surgery correction with duodenal-jejunal anastomosis.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Clinical mimicry: gastroesophageal disease masked by adverse drug reaction G. Meneguzzi1, L. Pompilio1, C. Caroselli2, I. Curreli3, G. Bruno1 1 Medicina Interna, Dipartimento di Medicina clinica e molecolare, A.O. S. Andrea, Facolta` di Medicina e Psicologia, Sapienza Universita` di Roma, Roma, Italy; 2Dipartimento di Emergenza, Azienda Ospedaliera Verona; 3Casa di Cura N.S. della Mercede, Roma, Italy

Adverse Drug Reactions (ADR) are more and more frequent in relation to the steady and progressive increase of the consumption of drugs, both the diagnosis and the therapy. Often clinical ADR pictures are not pathogenetically defined. In fact, apart from the well-known syndromes, diagnostic approaches are still not easy, due to the lack of reliable tests, based on rigorous scientific criteria. The aim of this study was focused to evaluate whether a suspected ADR can mimic a primary drug induced gastro-esophageal disease, or if this is likely subordinated, resulting from drug ingestion. In 4.950 subjects afferent the Allergology and Clinical Immunology Unit, 459 patients (9.27%) reported an ADR. Among these, we selected 50 subjects (10.9%), 17 males and 33 females, aged between 13 and 85 years (mean age 50.0 years). All subjects reported the onset of ADR, after many hours or days from the ingestion of drugs. These data are interesting to consider. First, in the selected patients the ADR never occurred the first or second drug administering (mainly NSAID followed by antimicrobials of the penicillin group). Second, there is the long time occurred between drug ingestion and the onset of clinical hypersensitivity reactions, mainly urticaria, sometimes with angioedema. Skin tests were negative evaluating the drug induced immediate or delayed hypersensitivity. In vitro tests were negative too. To assess whether the ADR can mask a clear or latent gastroesophageal alteration, we reviewed the medical history of patients that had symptoms and signs of gastro-esophageal disease. In fact, the endoscopy performed in 37/50 (74%) patients, documented: esophagitis, hiatus hernia, gastritis and peptic ulcer, alone or in combination. 14 cases (28.0%) resulted positive to Helicobacter pylori (Hp). The follow-up of 3 and 6 months, after appropriate therapy, led to the remission of the gastro-esophageal disease that mimicked ADRs. Also the Hp eradication with amoxicillin and clarithromycin did not cause any side effects. ADR represents a well-established frequent occurrence found in clinical practice. Without question mark the existence of the ADRs and in the absence of reliable diagnostic tests, we cannot ignore the possibility that the drug can cause an ADR, but considering an indirect and complex mechanism, such as neurogenic too, mediated by tachykinins released by sensitive fibers. Tachykinins induce mast cell mediators release causing immune-allergic like reactions. In this regard, as paradigmatic example it is to consider the aspirin that a part from the undoubted clinical efficacy, it is also known for its gastro-esophageal side effect.

Mean corpuscular volume and rised serum gastrin are sensitive markers of autoimmune atrophic gastritis E. Miceli, S.M.T. Durante, D. Padula, M.V. Lenti, V. Imbesi, C. Vattiato, M. Di Stefano, G.R. Corazza 1st Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy

S201 Background & Aim: Autoimmune atrophic gastritis (AAG) is an immune mediated chronic inflammation that involves the gastric body and fundus leading to hypo-achloridria and vitamin B12 deficiency. Vitamin B12 plays a pivotal role for the erythropoiesis, for the DNA synthesis, for the elimination of short-chain fatty acids and for homocysteine metabolism. The hypo-achlorhydria may also be responsible for malabsorption and leads to an increased serum gastrin and chromogranin A. The aim of this study was to evaluate the laboratory findings in patients with GAA who did not received any treatment. Patients and Methods: Seventy-six patients were eligible for this study (ratio F:M 2,8:1, mean age 58 ± 18 years, range 15-82 years). Diagnosis was based on histological ground according to the SydneyHuston classification and on the positivity of antiparietal cells antibodies. We collected blood tests, to evaluate cell blood count, lipid profile, iron balance, serum gastrin and chromogranin A. Results: At the cell blood count 46 patients had low hemoglobin levels (60.5%), 30 had macrocytosis (39.5%), 9 of them without anaemia. In 3 pts pancytopenia was also present. Low serum iron and ferritin levels were revealed in 12 pts (15.8%). Mean serum vitamin B12 level was 238 ± 160 pg/ml and vitamin B12 deficiency was present in 44 pts (57.9%). In none of the patients we were able to show low folate levels, but 22 of them were supplemented in the past because of hyperhomocysteinemia. Concerning with lipid profile, 28 pts (36.8%) presented hypercholesterolemia. Mean gastrin level was 795 ± 879 pg/ml, being [ 120 pg/ml in 68 pts (89.4%) and mean chromogranin A level was 154 ± 127 ng/ml, being [ 100 in 45 pts (59.2%). In particular, all the patients showed macrocytosis or hypergastrinemia or both of them. Conclusions: The AAG can onset with widespread manifestations. The laboratory findings may be useful to guide the diagnosis, especially when the clinical features are blurred. Until now no study had ever considered the laboratory findings in a systematic manner in patients with AAG. Although specificity should be checked in controlled studies, raised serum gastrin levels and macrocytosis turned out to have an absolute sensitivity (100% pts) in patients with AAG.

Atypical neuroleptic malignant syndrome L. Olivetto, M.C. Bertoncelli, R. Cantone S.C. Medicina Interna, Ospedale S. Andrea, Vercelli, Italy Diagnostic criteria for neuroleptic malignant syndrome (NMS) have been established and are widely accepted. NMS is a diagnosis of exclusion and other etiologies must be considered first. Differential diagnosis relies on 4 major criteria: hyperthermia, rigidity or other extrapyramidal symptoms; autonomic disturbances; mental status changes. Atypical presentations may also occur, particularly during treatment with atypical antipsychotics. It remains unclear whether these atypical presentations represent early or impending NMS. Case report: A 47 y.o. man with cognitive impairment and a longstanding psychiatric illness (behaviour disturbances with aggressiveness) presented to the Emergency Department (PD) with deep agitation. Previous medical history included hypertension and smoking. He was unmarried and lived with his parents, but two months before he had been hospitalized in a neighbouring town for a relapse of his psychosis. After amelioration, he went to a local nursing home, because his parents could not take care of him any more. On discharge medications included: carbamazepine 200 mg t.i.d.; clotiapine 100 mg t.i.d.; chlor-demethyldiaze-pam 1.2 mg t.i.d.; lorazepam 2.5 mg t.i.d.; bisoprolol 2.5 mg o.d.; valsartan-hydrochlorothiazide 320 mg/12.5 mg o.d.; flurazepam 30 mg at bedtime. Upon arrival in the ED, he remained agitated despite administration of chlor-demethyldiazepam 5 mg i.v., midazolam 5 mg i.v., propofol 50 mg i.v. and

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S202 promazine 50 mg i.m. for aggressiveness, and then he was transferred to the Psychiatric Department (PD). On admission in the PD, he still received lorazepam 4 mg i.v. and clotiapine 40 mg i.m. and finally he calmed down. His initial blood pressure was 180/120 mmHg, but later it dropped to 150/100 mmHg. Blood count and biochemical profile were normal, even if CPK was a little greater than normal (421 U/L). No other physical abnormal finding was reported and therefore home medications were not changed, but amyloride-hydrochlorothiazide 5 mg/50 mg was added. The day after a neurologist noticed that he had abnormal extrapyramidal movements of the head and the neck. He thought they were probably due to neuroleptics, but no decision was taken about them. After few hours, the clinical conditions deteriorated: the movements increased, with rude resting tremors and diffuse fasciculations, but only slight rigidity; he became agitated and confused and complained of muscle aches; B.P. was 230/110, H.R. 120 beats/min, temperature 37.7C; he was heavily cold sweated, but respiratory and abdominal examination was otherwise unremarkable. The morning levels of muscle enzymes (CPK 10570 U/L; CKMb 35.6 ng/ml; myoglobin 7255 ng/ml) resulted high, with not-increased level of troponin-I, and later they showed a further elevation (CPK 56300 U/L; CKMb 158.3 ng/ml; myoglobin 13772 ng/ml; LDH 1595 U/L). Serum transaminases were elevate too (AST 1331 U/L; ALT 360 U/L). Blood count revealed marked leukocytosis (19.3 9 103/L) with prominent neutrophilia (80%). Urynalisis and chest X-ray were normal. Blood and urine cultures were negative and there was no evidence of infection. ECG revealed only a sinus tachycardia. An arterial blood analysis was performed (pH 7.47; pCO2 30.2 mmHg; pO2 62.7 mmHg; P/F [ 300; HCO3 22 mmol/L; lactic acid 4.2 mmol/L). After nephrological and anesthesiological evaluation, it was agreed about an internist management. In addition to aggressive hydratation (saline and glucose solutions) alkalinization (oral sodium bicarbonate), furosemide, antibiotics (ceftriaxone) and EBPM (enoxaparin) prophylaxis, the neuroleptic regimen was discontinuated and a treatment for extrapyramidal adverse reaction and NMS was started, at first with biperidene 5 mg i.v. and diazepam i.v. t.i.d. and then with oral administration of orphenadrine 50 mg b.i.d. The patient fast ameliorated, leukocytosis quickly fade away and CPK gradually decreased together with other laboratory abnormalities. His performance status get better, his physical discomfort ceased and B.P. remained well-controlled. Finally, on 9th day after admission, agree with his will, we trasferred him to a hospital in his resident town for further rehabilitation. Discussion: This case illustrates one of the many clinical presentations of NMS. At first clinicians were worried about his alterated mental status and behaviour, regarded as an exacerbation of his psychiatric illness, but they were not awared of neuroleptic adverse effects, because the patient was very agitated and hostile. However, when the clinical course worsened NMS was suspected, even if the patient had only few findings suggestive of NMS (autonomic instability with sweating, tachycardia, elevated B.P., alterated consciousness, extrapyramidal symptoms, elevated CPK, leucocytosis), while major signs (muscle rigidity or lead-pipe rigidity, fever [ 38C) were lacking. The clinical presentation, indeed, did not fulfill the most commonly used criteria set for NMS, resulting in an uncertain diagnosis. Accordingly to this, neuroleptic medications were not immediately stopped and specific treatment of NMS was delayed. In the absence of the typical rigidity (although there were distonic-choreiform movements of the head and the neck) the diagnosis of NMS was put forward on the basis of the massive elevation of serum CPK (on the 2nd day after admission), and we believe that the patient had an atypical NMS. Atypical NMS remains a controversial entity. At the state of art, this diagnosis requires at least three of the four cardinal signs of NMS (fever, rigidity; autonomic disturbances; mental status changes). Consequently, this puts greater

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 emphasis on ancillary measures, such as CPK level, as we saw in our case. Median levels range from 1000 to 10000 IU/L, but extreme elevation are reported, up till 800.000 IU/L. So we believe that an approach more sensitive to atypical forms of NMS might facilitate earlier detection and treatment. Employing the criteria proposed by Nierenberg and coll. (Clin Pharm. Ther 1991; 50: 580) may be useful to prevent a dangerous diagnostic delay.

A dangerous trap in a young man suffering SLE P. Onorato, R. Terribile, G. Esposito, M.V. Guerra, G. Monsurro`, D. Scognamiglio, A. Izzo, R. Giunta, G. Lucivero V Divisione di Medicina Interna ed Immunoallergologia SUN, Napoli, Italy On June 2010 a 21 years old man suffering SLE complicated by lupus nephritis, diagnosed in August 2009 at our division, came to our attention. He has had about 7 days rise in temperature (38.6C CT max) arthromyalgia diffuse, cough and diarrhea (4 evacuations/day). Because of its autoimmune disease he took oral steroids, cyclophosphamide (50 mg 1 cpr 9 3 since one month), anti-hypertensives and lipid lowering drugs. At physical examination the patient appeared in good general conditions; however, pitting edema of extremities of legs, at chest auscultation a murmur vesicular mainly reduced specially on pulmonary bases, aphthous ulcers, high blood pressure (up to 160/90 mmHg), tachycardic pulse (up to 120 bpm) and fever (38.4C) were appreciated. Laboratory examinations showed: lymphocytopenia (200/mm3), thrombocytopenia (down to 5000/mm3), elevated transaminases (ALT 591 U/l, AST 253 U/l), severe hypoalbuminemia (1.9 g/dl), agammaglobulinemia (0 g/dl), cholinesterase expired (1233 U/l), and severe proteinuria (14 gr/24 h). The EGA showed a significant hypoxemia (pO2 64 mmHg, P/F 300, 35.5 DPAO2-PaO2 on ambient air at a respiratory rate of 22 breaths/minute) mixed alkalosis (pH 7.51, pCO2 38 mmHg, HCO3- 30.8 meq/l) and hypokalemia (K + 3.3 meq/l). The chest X-ray indicated a diffuse reticular-nodular accentuation of the pulmonary plot while chest-abdomen CT scan showed splenomegaly and interstitial lung commitment. Therefore we put forward the following clinical diagnostic hypothesis: bacterial sepsis, Pnuemocystis carinii pneumonia, systemic Leishmaniasis, iatrogenic toxicity, recovery of lupus disease with multi-organ failure. For the persistence of fever preceeded by shaking chills (T max 40C), blood cultures, urine culture, coproculture, BAL and screening for viral infections (including HIV) were performed and turned all negative; empirical therapy with antibiotics, antivirals, antifungals and intravenous immunoglobulins was undertaken with poor results. On suspicion of iatrogenic toxicity (elevated transaminases levels and severe immunosuppression), cyclophosphamide was suspended. The ANA antibody titer was 1:80, not trusted by the concomitant agammaglobulinemia. Taking into account the state of immunocompromised due to both the nephrotic syndrome and cyclophosphamide and the detection of signs of CMV infection during the previous hospitalization, the high anti-CMV IgG antibody titer (1/5744 with normal value \ 1/231) was interpreted as highly suggestive for reactivation of CMV infection. Therefore, we proceeded to the determination of CMV-DNA in plasma showing high viral load (3.9E + 5): we administered intravenous specific anti-CMV immunoglobulins and valganciclovir. The patient’s general conditions bettered: so he obtained a rapid defervescence, an improvement in lymphocytes and platelets count (respectively 2100/mm3 and 140 9 103/mm3) and an improvement in protein electrophoretic picture (albumin 3 g/dl, c globulin 1 g/dl). This case raises an important clinical question is how to manage the immunosuppressive therapy in autoimmune diseases with particular emphasis on the one hand the need to achieve adequate control of the

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disease and the other on the risk of exposing the patient to opportunistic infections by excessive immunosuppression, such as CMV, that in turn could adversely affect the immune response. Much more interesting it’s the relationship between CMV infection and SLE. Infact we could describe three patterns of association: 1) infection occurs during treatment and exacerbates pre-existing SLE; 2) symptoms arise due to CMV infection itself rather than an exacerbation of underlying SLE; 3) CMV infection directly provokes the onset of SLE.

Tacrolimus administration and female sex accelerate the development of fatty changes of the liver graft after liver transplantation F.R. Ponziani1, B.E. Annicchiarico1, M. Siciliano1, A. Avolio2, M. Garcovich1, I. Pennacchia3, F.M. Vecchio3, G.A. Gasbarrini4, A. Gasbarrini1 1

Internal Medicine and Gastroenterology; 2Surgery; 3Histopathology, Catholic University of Rome, Rome, Italy; 4Fondazione Ricerca in Medicina, Bologna, Italy

Introduction: Fatty changes of the graft (GFC) are common in liver transplanted (LT) patients (incidence 20-40%). GFC could lead to steatohepatitis and cirrhosis, even if in presence of an initial preservation of liver graft function. Aims & Methods: We retrospectively analyzed liver histology of LT patients, to describe the incidence of GFC and to determine the principle factors associated to GFC development. 81/222 patients, transplanted between September 1990 and March 2011, with an available liver histology after LT were included in the analysis. The mean age at LT was 49.7 years (14-64 ± 9.6), male/female 65 (80.2%)/16 (19.8%), 9/79 (11.4%) were transplanted for HBV, 44/79 (55.7%) for HCV, 17/79 (21.5%) for alcoholic, 9 (11.4%) for other causes of liver disease. In 34/79 (43%) patients the main immunosuppressor was cyclosporine, in 42/79 (53.2%) tacrolimus. Results: 43/81 (53.1%) of the investigated patients developed GFC in a mean time of 1716.6 days (7-6578 ± 1638.1) after LT. According to the NAFLD Activity Score (NAS) [1], 39/81 (48.1%) patients developed grade 0 (\ 5%), 36/81 (44.4%) grade 1 (5-33%), and 6/81 (7.4%) grade 2 ([ 33-66%) steatosis. Overall, patients receiving tacrolimus as main immunosuppressor showed a slightly higher tendency to develop GFC, even if not statistically significant, and GFC occurred in a shorter time (table 1); however, stratifying the data according to the severity of GFC, female sex seems to achieve the strongest effect (p = 0.040) on the timing of GFC development.

FACTOR

Sig.

HR

L/95% CI

U/95% CI

AGE C 60

0,592

1,275

0,524

3,103

Female SEX

0,286

1,530

0,701

3,340

Tacrolimus

0,031

2,160

1,074

4,342

EZIOL HCV

0,740

EZIOL HBV

0,763

1,185

0,393

3,575

EZIOL alcohol EZIOL other

0,782 0,299

0,885 0,558

0,374 0,186

2,096 1,678

The effect of female sex and tacrolimus administration on the timing of GFC development suggests the need of a more intense follow-up in these subgroups of LT patients. Reference 1. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ. Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41(6):1313-21

An unusual case of dilated cardiomyopathy associated with partial hypopituitarism A. Salzano1, E. Bobbio1, A.M. Marra1, M. Arcopinto1, D. Sirico1, D. Celentani1, F. Ferrara1, E. Bossone2, A. Cittadini1, L. Sacca`1 1

Dipartimento Medicina Interna, Scienze Cardiovascolari ed Immunologiche, Universita` di Napoli ‘‘Federico II’’, Napoli, Italy; 2 Dipartimento Cardiologia e Cardiochirurgia, Ospedale Universitario ‘‘Scuola Medica Salernitana’’, Salerno, Italy A 55-years-old woman was admitted to our Intensive Coronary Unit in February 2008 because of a community-acquired pneumonia complicated by acute heart failure. The patient was started on the ‘‘pneumonia protocol’’. Notwithstanding standard therapy for acute heart failure including nitrates, furosemide and digoxin, and the introduction of inotropic support, the patient was st ill hypotensive and for this reason she was admitted to the intensive care unit of our tertiary care hospital. A surgical intervention for aneurysmectomy of the left middle cerebral artery was performed in 2006. A complete hormonal panel showed low levels of early-morning serum cortisol and undetectable levels of serum IGF-1 without evidence of secondary gonadal failure (Table). Thyroid failure was partial insofar as TSH increased up to 10.9 lU/mL, indicating residual pituitary secretion. We next performed a GHRH + Arginin stimulation test for diagnosis of acquired GH deficiency. On top of optimized therapy for CHF that included beta-blockers, loop diuretics, CEI, nitrates, and low doses of aldosterone receptor antagonists, we added the following hormone replacement therapy: cortisone acetate, levotyroxine and, after 2 weeks, recombinant human GH (rhGH). The patient was re-evaluated after 6 months, and showed a remarkable improvement of clinical status and cardiovascular performance. She gained weight, approximately 2-3 kilograms, NYHA class shifted from IV to I. The hormonal profile displayed the normalization of the main axes as depicted in the table. Echocardiography detected a dramatic increase of both systolic and diastolic function. Cavity dimensions decreased accordingly and particularly impressive was the change in the end-systolic LV volume. The current case represents a very unusual dilated cardiomyopathy (DCM) with a severe symptomatic CHF in a patient with a hypopituitarism promptly responding to multiple replacement therapy. The peculiarities of the case report are many and include the following: 1)

2) Conclusion: Our retrospective series shows that more than half of LT patients develop almost mild GFC within the first five years after LT.

to our knowledge this is the first case of partial hypopituitarism associated with dilated cardiomyopathy, insofar as all previously reported cases only describe cardiomyopathies following panhypopituitarism; although hypopituitarism of various degree may develop in patients undergoing neurosurgery even far from hypothalamicpituitary region, most diseases occur following excision of primary brain tumors and not because of aneurysmectomy;

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S204 3) 4)

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the response to the replacement therapy was impressive, to a larger extent than reported so far; at variance with previous reports, we started almost simultaneously glucocorticoid, thyroid, and GH replacement therapy, and the GH dose was lower.

Table Echocardiography, cardiopulmonary exercise testing and hormones at baseline and after 6 months of therapy Baseline

After 6 months

Heart rate, bpm

110

80

Systolic/Diastolic Blood Pressure, mmHg

90/50

110/70 63

End-Systolic volume, mL

128

End-Diastolic volume, mL

148

103

Ejection Fraction, %

13

38

E/A ratio

1.57

0.82

E/E’

19

4.7

TSH, lU/mL

10.9

7.63

FT3, pg/mL

1

1.6

FT4, ng/dL

0.27

0.42

Early-morning cortisol, lg/dL

9.98

27.2

IGF-1, ng/mL

Unfeasible

140

ACTH, pg/mL

9.88

20.1

Maximal oxygen consumption, ml/kg/min

Unfeasible

14.4

Workload, watt

Unfeasible

39

discharged with diagnosis of idiopathic urticaria and steroid and antihistamines therapy was started. During steroid tapering she developed two others episodes of urticaria and generalized edema, the latter associated with abdominal pain and distension, diarrhea, fecal incontinence, arthralgias and worsening asthenia. She came to our attention for immunological evaluation. Serological tests for autoimmunity (ANA, anti-dsDNA and anti-ENA autoantibodies, ANCA) and the complement study (C3, C4, C1q, quantitative and functional C1-inhibitor, anti-C1q precipitins) showed no abnormalities. Skin biopsy excluded vasculitis, but showed an intense eosinophilic infiltrate. Further endoscopic evaluation of the gastrointestinal tract showed nodular pattern of duodenal bulb mucosa, mild villous atrophy, hyperemia and swelling of jejunal mucosa. Biopsies of duodenum revealed Giardia lamblia trophozoites. Rare Giardia cystis were then detected in stool specimens. Treatment with metronidazole 250 mg thrice a day for 7 days was given. After initial remission, symptoms reappeared one month later. An additive test on stool was positive for Giargia lamblia. The patient received once more metronidazole 500 mg thrice a day plus albendazole 400 mg once a day for three weeks and symptoms totally disappeared. This case report underlines that protozoans should be considered in the etiology of chronic urticaria and angioedema, especially when associated with intestinal symptoms. Stool examinations should be routinely performed in these patients, although negative results do not rule out G. lamblia as the causative agent. In case of persistent symptoms and negativity of stool examinations, biopsy of the small intestine may be required to detect the parasite.

Elderly onset Henoch-Schonlein purpura: not just a second childhood. A case report A. Soriano1, U. Vespasiani-Gentilucci2, G. Galati2, C. Mazzarelli2, P. Gallo2, A. De Vincentis2, A. Afeltra1, A. Picardi2 Medicina Clinica e Reumatologia; 2Medicina Clinica-Epatologia, Universita` Campus Bio-Medico, Roma, Italy

1

A case of chronic urticaria, an unexpected culprit M.C. Sielli1, G. Stagnozzi1, E. Kamberi1, C. Massaccesi1, A. Zoli2 1 Scuola di Specializzazione in Allergologia e Immunologia Clinica, Universita` Politecnica delle Marche; 2Servizio Regionale di Immunologia Clinica e Tipizzazione Tessutale, Azienda OspedalieroUniversitaria Ospedali Riuniti di Ancona, Ancona, Italy

We report the case of a 37-years-old woman, with recurrent episodes of extended urticaria and facial and legs edema, associated to asthenia, flatulence, abdominal distention and cramps. The patient history included an eradication therapy for H.Pylori infection and an episode of acute gastroenteritis with diarrhea in the last year. Before our observation she underwent several investigations during two hospitalizations. No signs of heart, renal or hepatic failure were detected. Total IgE resulted lightly increased. Skin prick tests and serological tests excluded food allergy. Serum tryptase and inflammatory markers were normal. Three consecutive stools specimens were negative for parasites cystis or trophozoites, as well as occult blood test. Fecal calprotectin was normal. An endoscopic evaluation of the gastrointestinal tract showed lymphocytic epithelial infiltration of duodenal mucosa without villous atrophy, which leaded to the suspicion of celiac disease type I. Serum immunoglobulins were normal, except a slight decrease of IgG1 subclass; anti-transglutaminase, anti-endomysial antibodies and HLA DQ2-DQ8 alleles were absent, thus celiac disease was ruled out. Chest and abdomen imaging study excluded malignancies. She was

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Presentation: A 81-year-old Caucasian woman, affected by diabetes mellitus and mild arterial hypertension, presented with a history of six months of purpuric rash of the extremities, occurred after an ‘influenza- like’ syndrome characterized by fever (T. max 38C), diffuse abdominal pain and diarrhea. Fever and gastro-intestinal symptoms spontaneously resolved after one week, while the rash persisted with periodic pousse`e. 10 days after, she was hospitalized because of oedema, erythema and tenderness of the left leg. An angio-TC scan of the abdomen and low extremities showed extensive thrombotic occlusion of left femoral-iliac venous axis, with partial involvement of distal tract of inferior vena cava. A skin biopsy was performed, showing leukocytoclastic vasculitis with immunoglobulin A (IgA) deposits and C3 in the vascular wall. Anticoagulation therapy was started and she was referred to our institution for further workup and management. On admission, physical examination revealed multiple palpable purpuric lesions, regular in outline, that were distributed predominantly to the legs and arms but involving also the buttocks and the abdomen. The patient denied recent medication changes, travel, and use of over-the-counter medications as well as past thrombotic events. Laboratory tests revealed a mild normocytic anemia, elevation of erythrocyte sedimentation rate (120 mm/h with normal value 0 – 20) and a moderate renal failure (stage II according to Cockcroft-Gault formula) with persistent dysmorphic hematuria and proteinuria in a non-nephrotic range. Immunological, virological and bacterial screening tests were all negative. In order to detect a possible coexisting thrombophilic state, the complete panel for hereditary and acquired thrombotic risk factors was performed. We

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 found only mild elevation of homocysteine (19 mmol/L with normal value till 11 mmol/L) in absence of methylentetrahydrofolatreductase (MTHFR) mutation or folic acid or vitamin B12 deficiency. Diagnosis and decision making: To confirm the hypothesis of leukocytoclastic vasculitis, and given the persistent microscopic dysmorphic hematuria with mild alteration in renal function tests, we decided to perform a renal biopsy that revealed diffuse mesangial cell proliferation and crescent formation. Immunofluorescence showed predominantly mesangial IgA staining, consistent with HenochScho¨nlein (HS) nephritis. Treatment: Since HS nephritis is a very rare disease in the elderly, no standardized therapy is available. Treatment with corticosteroids or other immunosuppresants such as cyclophosphamide has been reported with varying success. Our patient received methylprednisolone 0.35 mg/Kg for four weeks achieving complete resolution of the skin rash, an improvement of renal function and disappearance of microscopic hematuria at urinalysis. This condition persisted also when steroid tapering was begun. Discussion: Renal failure with progression to end-stage disease is a long-term complication in up to 27% of adult patients with HenochScho¨nlein Purpura (HSP) with renal involvement. The predictors of a poor renal course in adults have been proposed, such as high creatinine levels at onset, protei-nuria greater than 1 g/day, arterial hypertension, increase of proteinuria during follow-up, extracapillary proliferation in the renal biopsy, interstitial fibrosis and tubular atrophy. Considering the advanced age, the comorbidities of our patient and the absence of the predictors of a poor renal prognosis, we decide to start methylprednisolone at a lower dosage, with improvement of renal function and a complete resolution of skin rash. Furthermore, evidence of deep vein thrombosis as a complication of HSP is an extremely rare event and limited to sporadic case reports. Some authors supposed that HSP itself may induce a prothrombotic state and increase the risk of thrombotic events, mainly in patients who have other risk factors. However, in our case screening for prothrombotic risk factors was negative, except for mild hyperhomocysteinemia of uncertain clinical significance. Conclusions: HSP should be considered in the differential diagnosis of leukocytoclastic vasculitides even at the extremes of age, if at least a non-thrombocytopenic palpable purpura on the lower limbs and buttocks is present. Unlike childhood HSP, a particular attention has to be given to renal disease for the potential morbidity and mortality in this older population, although in our case renal involvement seemed to be less aggressive and responsive to lower doses of steroid therapy. On the other hand, our patient experienced a deep vein thrombosis as a severe and rare complication of HSP, confirming that hyperactivation of coagulation system might be more significant in these patients. Therefore, we suggest that in case of HSP to rule out an occult thrombotic event is mandatory, especially in presence of additional thrombotic risk factors. Reference Kellerman PS. Henoch-Scho¨nlein purpura in adults. Am J Kidney Dis. 2006;48(6):1009-16

Asia syndrome: giant cell arteritis and polymyalgia rheumatica after influenza vaccination. Experience of 10 cases A. Soriano, E. Verrecchia, A. Marinaro, M. Giovinale, C. Fonnesu, R. Landolfi, R. Manna Periodic Fever Research Center, Internal Medicine Department, Catholic University of Sacred Heart, Rome, Italy Polymyalgia Rheumatica (PMR) is inflammatory rheumatic disease not rare in people over the age of 50 years, characterized by pain and

S205 morning stiffness in the shoulder and pelvic girdles, along with evidence of an underlying inflammatory reaction; sometimes PMR is associated with Horton’s Arteritis (HA). There has been reported the association of PMR with HLA-DRB1*0401 and DRB1*0404 alleles, and there is a limited number (11) of reports of PMR following influenza vaccination (IV) in genetically predisposed subject having alleles at HLA-DRB1 locus. Recently, a new syndrome called ‘ASIA’-autoimmune/auto-inflammatory syndrome induced by adjuvants has been proposed by J Schoenfeld, correlating some autoimmune pathology to vaccinations. We report 10 cases of previously healthy patients who developed PMR/HA, within 2-4 months after IV. Immune adjuvants may play a key role in induction of post-vaccination adverse events, such, as in our cases, a vasculitis-related disease. On the other hand, a role of the individual susceptibility has to be valued, which can justify the rarity of these events, despite the several kind of environmental factors (i.e. infectious triggers, ‘‘natural adjuvants’’, etc.). Furthermore, the identification of an individual susceptibility to post-vaccination adverse events, by studying the HLA system as well as Toll-like receptor signalling pathways, could be useful to clarify the correlation between molecular mechanisms and clinical patterns of the this new ‘ASIA’ syndrome.

The presence of diabetes reduces SVR after antiviral therapy for post-transplant HCV recurrence V. Vero1, M. Senzolo2, L. Pasulo3, F.R. Ponziani1, R. Vigano`4, M. Marino5, M.F. Donato6, M. Rendina7, P. Toniutto8, M. Cescon9, E. De Martin2, L. Miglioresi10, V. Giannelli11, D. Di Paolo12, S. Fagiuoli3 on Behalf of the AISF Study Group (Recolt) 1

Medicina, Gemelli, Roma; 2Gastro, Padova; 3Gastro, Bergamo; Gastro, Niguarda Milano; 5Gastro, Modena; 6Gastro, Milano; 7 Gastro, Bari; 8Gastro, Udine; 9Chirurgia, Bologna; 10Gastro Forlanini, Roma; 11Gastro, Tor Vergata, Roma; 12Gastro, Sapienza, Roma, Italy 4

Background: Hepatitis C recurrence after liver transplantation is a major cause of both graft failure and reduced survival. At present, the antiviral treatment of HCV recurrence is the only available strategy in the attempt to prevent progression of the disease: the achievement of SVR(sustained virological response) appears to improve both histological picture and patient survival. Diabetes and insulin-resistance are well known negative prognostic factors for antiviral treatment in the non-transplant setting. Few data are available in the transplant setting. Aim: To evaluate the impact of diabetes on SVR in liver transplant recipients undergoing an antiviral treatment for HCV recurrence. Patients and Methods: data from a multicenter database of 464 patients transplanted for HCV-related ESLD in 12 Italian Centers from 1992 to 2008 were retrospectively collected. All patients underwent a combination treatment with interferon) and Ribavirin for histologically proven HCV recurrence. Mean age at LT was 53,5 yrs, genotype 1: 73,9%. 151 patients (32,5%) were diabetics. Results: Overall SVR in our population was 34,1% (158 patients). SVR was 25,3% in diabetic patients compared with 40,6% in non diabetics (p = 0,04). Among diabetics, the use of insulin (71% of the diabetics) was associated with a lower rate of end of treatment response (EOT): 49% vs 67,4% in non-insulin dependent diabetics (p = 0,04). The pre treatment viremia is the only factor that significantly differs between the two group (diabetics vs non diabetics patients: p = 0,01); whereas no differences in term of donor and recipient characteristics, genotype, duration of antiviral therapy, distance from olt, interval oltrecurrence, pre treatment fibrosis, emerged at the analysis.

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S206 At multivariate analysis the presence of diabetes was confirmed as independent negative predictor of SVR (p = 0,05). Conclusions: The presence of diabetes and the need for insulin emerge as negative prognostic factors for the response (SVR and EOT respectively) to antiviral treatment for HCV recurrence post-liver transplantation.

Clinical Cases for the Gymnasium Session Abdominal pain from Africa S.M. Atzori, S. Cambule, F. Pani, M. Carbini, S. Carta, C. Mulas, M.P. Ruggiu, M.A. Bella, F. Tanda, G. Vidili, G. Delitala Clinica Medica Cliniche Universitarie Sassari, Italy A 25-years-old man was admitted to our department with constant abdominal pain, fever to 39C and nausea. The patient was born in Senegal until immigrating in Italy ten years before admission; thereafter he visited Dakar annually. He complained of a vague abdominal discomfort, associated with nausea but not vomiting, not productive cough and decreased appetite since he had been in Dakar the month before admission. Two weeks before admission developed intermittent fevers, with temperatures up to 37,7C. One day before admission, pain in the lower quadrant developed and temperature rose to 39,1C. The patient had no known co-morbidities and no history of hospitalization. Physical examination revealed direct tenderness in the lower quadrant of the abdomen. There was no note of lynphadenopathies and the rest of the physical exam was unremarkable. Routine laboratory data showed hemoglobin of 10 g/dl and normal leucocyte count, platelets, electrolyte, renal and liver function tests. Urinalysis revealed leukocytes (100 white cells per high-power field), and a urine culture grew coagulase negative Staphylococcus; blood cultures were sterile. Ciprofloxacin and Pantoprazole were administered. Abdominal x ray showed a few dilated loops of bowel with some air fluid level. Chest x ray was normal. Ultrasound examination of the abdomen showed the presence of interloop ascitic fluid, mesenteric thickening with fibrotic brench that were referred to a chronic peritonitis, mesenteritis of jejunal and ileum with conglomerated loops, enlarged lymphnodes in the small bowel mesentery. Was performed an exploratory paracentesis that revealed the presence of ascitic fluid exudates. Differential diagnosis at this point includes four groups of disorders: infectious disease also in relation to the history of immigration of the patient from a tropical area, inflammatory bowel disease, autoimmune disease and lymphoma of the small intestine. Test results for antinuclear antibodies, antibodies to smooth muscle, double stranded DNA, SSA, SSB, Sm, RNP, Scl antigens, anti cyclic citrullinated peptide IgG antibodies, anti neutrophil cytoplasm antibodies were negative. Temperature fell into normal range when Meropenem and Amikacine were administered intravenously. The abdominal pain was improved although the patient continued to report diffuse discomfort associated with nausea. Colonscopy revealed no alteration. Test results were negative for hepatitis A, B and C, Human Immunodeficiency Virus, Syphilis, Bartonella species, Legionella Borrelia, Toxoplasma, Herpes Simplex Virus, Parvovirus, Cytomegalovirus, Ehrlichia, Anaplasma, Rickettsia, Coxiella, Brucella, Leishmania, Epstein Barr, Parvovirus, Salmonella, Shigella. We focused our diagnostic hypothesis on peritoneal tuberculosis. Skin test with PPD, Quantiferon test, urine, fecal, ascitic fluid culture were negative for Mycobacterium tuberculosis infection. A contrast-enhanced Tomografy scan of the abdomen showed dilatation of mesenteric loops with hypotonia of the wall, conglomeration of jejuna and ileal loops and fluid among the loops.

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Exploratory laparotomy was performed showing thickening and stiffness of parietal peritoneum with increased vascularization that were referred to chronic inflammation, conglomeration of ileal loops, thickening of visceral peritoneum with the presence of several whiteyellow nodules. Histologic examination on biopsy showed the presence of granulomatous inflammation with giant cells. Biopsy culture was positive for Micobacterium tuberculosis. Standard chemiotherapic treatment with Rifampicin, Isoniazid, Pyrazinamide and Ethambutol was started. Abdominal tuberculosis should be considered in patients from developing countries with abdominal pain. Diagnosis is difficult because of its lack of specific symptoms and it is limited by the invasiveness and expense of the procedures needed to obtain appropriate samples for histology or culture. Ultrasonography is a noninvasive technique, especially useful for detecting ascites and asymmetric bowel wall thickening. Laparoscopy, laparotomy or percutaneous biopsy are required in most cases.

Respiratory distress from the bowel S.M. Atzori, C. Mulas, G. Mulliri, S. Cambule, F. Pani, S. Carta, M. Massidda, M.P. Ruggiu, G. Piga, G. Delitala Clinica Medica Cliniche Universitarie Sassari, Italy A 55-years-old men was admitted in our department because of upper respiratory symptoms and fever up to 37,6 C. The patient had been in his usual state of health until 3 days earlier, when subjective fever, fatigue, headache, nasal and sinus congestion, sore throat, and a nonproductive cough developed. He did not have chills, gastrointestinal symptoms, shortness of breath, wheezing, night sweats, or chest discomfort. The patient had a history of schizophrenia with mental retardation and he resided in a long term care facility for patients with mental illness. Medications included Lorazepam, Olanzapine, Haloperidol, Diazepam, Duloxetine. On examination, the patient appeared to be alert, cooperative but not well articulate, without respiratory distress. The skin was pale. The blood pressure was 164/75 mm Hg, the pulse 81 beats per minute, the temperature 38C, the respiratory rate 25 breaths per minute, and the oxygen saturation 85 to 90% while the patient was breathing ambient air. The body-mass index (BMI) was 27. There was no clubbing, cyanosis, or ulcerations. On auscultation, there were coarse rales at the lung right base with no rales or wheezing. Routine laboratory data showed hemoglobin of 10 g/dl and increased leucocyte count, normal platelets, electrolyte, renal and liver function tests. A chest radiograph revealed elevation of right hemidiaphragm, atelectasis and opacity in the base of the right lung, a small pleural effusion on the right side. Blood cultures were sterile. We limited our hypothesis on infectious processes and in particular on hospital-acquired pneumonia. Ciprofloxacine was administered. After one week of hospitalization the temperature was still present and repeat radiography performed showed that the opacity was increased. We focused our attention on two different hypothesis: tuberculosis infection or lung cancer. Quantiferon test was positive for M. tuberculosis infection and pleural fluid culture was performed. Temperature fell into normal range when Ciprofloxacine, Meropenem, Amikacin and Azithromycin were administered, although opacity and pleural effusion were still present. TC of the chest showed opacity in the right lobe and a small right pleural effusion. Was performed a Magnetic Resonance (MR) of the chest that showed a marked enhancement of the right lung. Bronchoscopy with bronchoalveolar lavage and transbronchial lung biopsy was negative for neoplastic process. Culturefor Mycobacterium tuberculosis was negative. Bronchoalveolar lavage culture grew Enterococcus faecalis. Levofloxacin was administered.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 This case demonstrates the importance of distinguishing and well treating hospital-acquired pneumonia. The patient’s clinical and social profile made hospital-acquired pneumonia a major issue to consider. Pneumonia caused by Enterobacteriaceae should be considered in the differential diagnosis in patients resident in long term care hospitals.

S207 mobilization, gaining full autonomy in the activities of daily living. Six months after, the results of the genetic tests run before the patient had come to our department declared the absence of the BrownVialetto-Van-Leare syndrome.

Hemoconcentration, low albumin levels and monoclonal gammopathy with hemodynamic impairment: a difficult diagnosis A misclassification of a rare neurological disease, dramatically improved after medical therapy M. Battistioli, G. Realdi Universita` degli Studi di Padova, Dipartimento di Scienze Mediche Chirurgiche, c/o Clinica Medica 1, Padova, Italy A young woman aged 21 was admitted to our department for colicky abdominal pain. After exclusion of any kind of surgical abdominal emergency, the patient was evaluated for her general condition. She reported a weight loss of 13 kg over the last year, with a body weight of 37.8 kg and BMI of 14.2, alternating bowel function, fatigue, anorexia and extreme muscle weakness. The patient also had a diffuse muscular atrophy with claw hand, walking impairment, muscles and tongue’ fasciculations, and extreme exhaustion of respiratory activity, possible only with the help of the accessory muscles. Six months before, the patient was admitted to the neurological department of another hospital where she was clinically diagnosed of Brown-Vialetto-Van-Leare syndrome, waiting for the genetic test on DNA extracted from blood to verify the presence of the disease. Over time and progressively from childhood the patient was placed in a very restricted diet because of several episodes of erythema with crusts and urticaria attributed to food allergies. Our first diagnostical hypothesis was a malabsorption syndrome. As a matter of fact the neuropsychiatric assessment reported an involvement of both the upper motor neuron (VIII, XI, X) and the lower one widespread (mainly the upper limbs) but it questioned the diagnosis of rare neurological disease at the same time. This because the genetic tests had to be run to make the final diagnosis. All available tests in order to exclude diseases that could lead to malabsorption (celiac disease, intolerance to carbohydrates, tropical sprue) were run. All the results were negative, as well as autoimmunity and immunological examinations. The values of copper and zinc were altered, documenting severe reduction, as well as it was reported a modest reduction of vitamin A. The values of the other water-soluble and fat-soluble vitamins were reported within normal limits. The conversation the patient had with the fellow psychiatrist, performed to rule out a possible eating disorder like anorexia, showed a constrained state of anxiety with gastrointestinal somatization. It was confirmed to be possible that some of the patient’s accompanying symptoms and choices over food to be eaten were the expression of a personal refusal and discomfort towards some members of her family. At this purpose, the patient had spoke about some troubles inside her family on several occasions without further explanations. For the reasons explained above, we have interpreted the symptoms described as the result of a totally inadequate diet that the patient decided to start years before, facing herself with a poor cultural and familiar background, thus leading to a secondary neurological involvement. For this reason, we have started a high-calorie diet therapy of 2100 kcal per day with 80 g protein per day, enriched with vitamins and free metals, trying to recover in the diet all the things that she had excluded. With this therapy, the patient reported a weight gain of about 2 kg during the three weeks of hospitalization and a further, even if less dramatic, weight gain over the following six months. Today’s weight is up to 43 kg. Our recommendation to continue at home the physical and the respiratory therapy that had been started in our department, has revealed to be effective: the patient reported an improvement in breathing and in

G. Berti De Marinis, I. Bertozzi, F. Tezza, E. Allemand UOC Medicina Interna, Dipartimento di Scienze Mediche e Chirurgiche, Universita` degli Studi di Padova, Padova, Italy In November 2009 a 40-years old white male was urgently hospitalized for orthostatic syncope secondary to severe hypotension. In the previous few days he experienced profuse sweating and oliguria after intense running effort. Three days before admission he even presented fever, sore throat and flu-like syndrome. His medical history was relevant for hypothyroidism on hormone replacement therapy and previous bilateral renal colic episodes due to kidney stone treated with lithotripsy. Physical examination showed pallor, redness of the pharynx, hardening of the calves, body weight 102 kg, no signs of acute bleeding. His vital parameters at admission were: arterial blood pressure (BP) 92/54 mmHg, heart rate (HR) 108 bpm, oxygen saturation by pulse oximetry 100% without oxygen supplementation, body temperature 37.6C. Blood tests revealed hemoglobin (Hb) 227 g/L, hematocrit (Ht) 64.3%, white blood cells 18.84 9 109/L with neutrophils 14.71 9 109/L, serum creatinine 151 lmol/L, blood urea nitrogen 10.5 mmol/L, C-reactive protein (CRP) 13.82 mg/L, lactic dehydrogenase 739 U/L, d-dimer 508 ng/L and metabolic acidosis with normal anion gap and lactic acid; hepatic function, troponin I and creatine-kinase were normal too. Electrocardiography, chest radiograph and echocardiography were negative as well as lower limbs CUS exam and no splenomegaly was found on ultrasound abdominal examination. An initial diagnosis of dehydration with hemoconcentration was suggested: he was administered with 3.5 L of saline and 500 ml of colloids with a progressive slow normalization of blood pressure values and restoring of adequate diuresis. However elevated Ht persisted high with values of about 60%: we performed a therapeutic phlebotomy to prevent any hyperviscosity complications with good laboratory response. Pulmonary embolism was excluded by an emergent multislice CT. Septic shock was ruled out because of relatively low levels of CRP, negativity of procalcitonin and blood and urine culture, absence of organ damage. Erythropoietin assay and the research of the V617F Jak2 mutation were both negatives, excluding a myeloproliferative disorder. Further laboratory and instrumental analysis performed in the following days showed low total serum protein (49,2 g/L) with low albumin concentration (27.4 g/L) and the presence of an unmeasurable monoclonal gammopathy IgG/k with elevated b2-microglobulin (2.65 mg/L) and Bence Jones proteinuria; still they excluded the presence of nephritic syndrome, H1N1 influenza virus infection, autoimmune rheumatic disease (RAAS), occult malignancy, endocrine dysfunction. We underestimated all of these findings, because they didn’t seem related to the clinical presentation. The patient was then discharged with a diagnosis of ‘‘dehydration with secondary erythrocytosis’’. During the following months he experienced almost every week episodes of peripheral edema and oliguria with body weight gain of about 5 kg, spontaneously resolving over 3-4 days with polyuria. He was twice admitted to the hospital, in both cases with erythrocytosis treated with saline infusion. He was completely revaluated to newly exclude RAAS, myeloproliferative disorder and paraneoplastic syndrome. Further insights performed even excluded systemic mastocytosis, ereditary angioedema and pheochromocytoma. In April 2010 he was readmitted in our unit for fainting, dispnea, hypotension (BP

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S208 105/62 mmHg), palpitations (HR 103 bpm), and erythrocytosis (Hb 222 g/l, Ht 62.4%). Physical examination revealed pretibial and periorbital edema. Renal and liver function and urinalysis were normal. Considering the recurrence of symptoms we searched for a nephrologist consult who suggested a diagnosis of Systemic Capillary Leak Syndrome (SCLS). The patient was administered with intravenous immunoglobulin (IVIG) 100 g/die for 2 days, repeated after 6 weeks. Continuative treatment with aminophilline 200 mg and clenbuterol 0.02 mg twice a day was instituted with temporary resolution of recurrent episodes. After five months however he experienced recurrence of the symptoms again responsive to IVIG. Because of the presumed immunological pathogenesis of the syndrome, an attempt with rituximab was tried with no effect. He has already experienced 12 relapses by now. SCLS is a rare disease with unknown pathogenesis and potentially fatal complications. Differential diagnosis is difficult due to its rarity and the poor knowledge of the syndrome; many other more likely pathologies must be excluded, however it should be taken into consideration whenever hemodynamic impairment with hemoconcentration, low albumin levels and monoclonal gammopathy is present.

Two deadly conditions and a difficult decision

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 cava filter to prevent further embolization, allowing suspension of anticoagulation therapy. Poor data are available from the literature dealing with bleeding risk due to anticoagulation therapy on stabilized chronic aortic dissection; revision of medical literature even suggested that antithrombotic drugs might be beneficial in patients with acute aortic dissection. After multi-disciplinary consult with vascular surgeons and angiologists we agreed to continue with anticoagulation therapy only, due to possible renal impairment related to further administration of iodinated contrast agent. After the acute episode patient hemodynamic status improved progressively with normalization of arterial blood pressure: antihypertensive drugs, temporarily suspended, were dosed to maintain arterial blood pressure on low-normal values. Patient was discharged from our clinic with fondaparinux once daily. In clinical practice evaluating risk–benefit ratio on every therapeutic intervention is fundamental. In our patient the risk related to acute pulmonary embolism relapse, if anticoagulation therapy was not prescribed, would have been higher than the risk due to aortic rupture. Moreover death risk related to aortic rupture is very high itself, even in the absence of factors that predispose to bleeding. Therefore in this specific case we decided to administer anticoagulant drugs in the belief to drastically reduce pulmonary embolism risk despite low increase of death risk due to aortic rupture.

G. Berti De Marinis, N. Vitturi, M. Arboit, F. Simoni, G. Realdi Policlinico Universitario di Padova, Clinica Medica I, Padova, Italy

A case of severe hypergastrinemia and gastric neuroendocrine tumour

A 75-years old woman was admitted to our clinic for an hypertensive crisis: symptoms consisting in nausea, headache and dizziness had begun a few hours earlier after a magnetic resonance angiography that she routinely did since 2 years for follow-up of chronic dissection of thoracic and abdominal aorta. Her past medical history was also relevant for previous left nefrectomy for polycystic kidney complicated by pyelonephritis, arterial hypertension, dyslipidemia, allergy to iodinated contrast agents consisting in urticaria. On admission physical examination confirmed high arterial blood pressure (210/97 mmHg). Mild anxiety state was evident and cardiovascular and neurological examination were completely negative. Laboratory exams showed mild chronic renal failure (creatinine 108 lmol/l). Cerebral CT was negative for intracranial bleeding. The patient was treated with labetalol infusion and diazepam orally with good response of arterial blood pressure; in the following days standard antihypertensive therapy was improved with stabilization of blood pressure values. The patient was not any longer symptomatic and discharge was planned on the fourth day after admission. The night before discharge the patient complained sudden onset of palpitations and dyspnea, associated with episodes of chest pain, headache and nausea; blood pressure was high at first (210/ 120 mmHg) then rapidly lowering (to 70/40 mmHg), heart rate and oxygen saturation by pulse oximetry were normal (70 bpm and 100% while breathing room air respectively): she was treated with colloids with hemodynamic stabilization and due to the very high clinical suspicion of aortic dissection she underwent urgent CT angiography after premedication with intravenous steroids and H1- and H2inhibitors: with our great surprise the exam showed pulmonary embolism involving segmental and sub-segmental posterior-basal pulmonary artery branches for right lower lobe with stability of the aortic state. The exam was complicated by worsening of renal function related to infusion of iodinated contrast material, then enhanced by hydration therapy. Ultrasonography resulted negative for deep and superficial venous thrombosis. Anticoagulation therapy with fondaparinux was immediately started. Given the high bleeding risk due to history of chronic aortic dissection, all at once we hypothesized the placement of a definitive vena

M. Biolato1, S. Alfieri2, G. Gasbarrini1

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1 Institute of Internal Medicine; 2Department of Digestive Surgery, Catholic University, ‘‘A. Gemelli’’ Hospital, Rome, Italy

Here we report a case of a 61-years old italian woman presented to outpatient clinic with a three-months history of epigastric pain especially between meals, heartburn, early satiety and dyspepsia. The patient had an history of chronic lymphocytic thyroiditis, osteoporosis and small intestinal bacterial overgrowth. Her current medications included rifaximin, metronidazole and aluminium-magnesium hydroxide. The physical examination revealed a normal nutritional state and hepatomegaly. Laboratory tests revealed: serum gastrin 1900 pg/ml (reference range, 30-115), hemoglobin 11,6 g/dl (reference range, 12-16 in women), vitamin B12 level 139 pg/ml (reference range, 158-600) and Internationalized Normalized Ratio 1,34 (reference range 0,8-1,2); because of this, she started phytonadione 10 mg/d. Other laboratory-test results (including the white-cell count and the differential count, erythrocyte sedimentation rate, serum levels of electrolytes, glucose, total protein, albumin, globulin, cholesterol, lipids, folate, ferritin, amylase, lipase, tests of renal, liver and thyroid function, serum neuron-specific enolase, chromogranin A, 5-hydroxyindoloacetic acid, CEA, CA 19-9, CA 125, and gastric parietal cell and intrinsic factor antibodies) were normal. Urea breath test for Helicobacter pylori infection was negative. Upper gastrointestinal endoscopy was performed. A 2 cm single sessile protruded-type polyp was found in the stomach. Microscopical examination showed in the gastric mucosa clumps of small size round-oval shaped cells with areas arranging in a trabecular or solid pattern. There were no area of necrosis and the KI-67 index was 3%. Immunohistochemical staining showed that the cancer cells were positive for neuron-specific enolase, cytokeratin and synaptophysin. The findings were those of a well differentiated neuroendocrine carcinoma (carcinoid tumor). Mild chronic atrophic gastritis and intestinal metaplasia was present in surrounding, non-neoplastic tissue. Thiazine staining for H. pylori was negative. Total body Computed Tomography (CT) showed no evidence of metastases and confirmed an hypervascular 1,7 9 1,3 cm

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 polyp in the stomach. Patient underwent a gastric tangential resection. Microscopical examination confirmed a well-differentiated, low grade, neuroendocrine tumor of the stomach infiltrating the submucosal layer with microvascular invasion. The margin of the resection were free of disease. The patient’s post-operative course was uneventful and she remained in a good clinical conditions. Six months later, serum gastrin was 2011 pg/ml. A total body CT scan and an upper gastrointestinal endoscopy excluded disease’s recurrence. Gastric antral biopsy showed mild chronic atrophic gastritis and intestinal metaplasia. Staining for H. pylori was negative. Immunohistochemical staining for cytokeratin and synaptophysin showed mild hyperplasia of neuroendocrine gastric cells. No tumor recurrence was revealed. The clinical picture was suggestive for an hypochlorhydria-related hypergastrinemia with subsequent develop of a non-secreting carcinoid. Figure Abdomen CT scan showed a gastric polyp with arterial enhancement and an apical area of necrosis.

S209 Cardiac catheterization: presence of an intra-atrial septum defect with a bidirectional shunt; normal pO2 in the right ventricule (pO2 33 mmHg), in the pulmonary artery (pO2 34 mmHg) and in the upper right pulmonary vein (pO2 90 mmHg); significantly reduced pO2 between in the left atrium (pO2 56 mmHg) and in the systemic arterial circulation (pO2 60 mmHg). These investigations didn’t show any clues of pulmonary causes responsible for hypoxemia, while right-to-left shunt at atrial level could not completely explain the severity of hypoxemia. In literature are described similar cases, in which in addition to a right-to-left shunt is present a difference in pO2 between right and left pulmonary veins, not well explained by the authors. These alterations may contribute to arterial hypoxemia. Finally, the patient was proposed the placement of a patch to correct the atrial septal defect. References 1. Kanji Iga MD, Chisato Izumi et al. Partial Pressure of Oxygen is lower in the left Upper Pulmonary Vein than in the right in adults with atrial septal defect. Chest. 1999;115:679-83 2. Fouty BW, Lynch DA et al. Hypoxemia explained 36 years later. Chest. 2001;120:1739-41

Severe muscle weakness during thyrotoxicosis: causal or casual relationship? M. Bovio, E. Nazzari, M. Grandis, G. Murialdo, P. Ameri Clinica di Medicina Interna 2, San Martino, Genova, Italy

An unexplained case of severe chronic hypoxemia L. Borgognoni, M. Bonini, S. Schiavetto, A. Russo, V. Fontana, T. Villani, P. Marinelli, A. Paris, F. Vaccaro, P. Palange Universita` di Roma ‘‘La Sapienza’’, Policlinico Umberto I, Dipartimento di Sanita` Pubblica e Malattie Infettive, UOC Medicina Interna I, Roma, Italy A 53-years-old, caucasian man, was admitted to our Hospital for a worsening of dyspnea. Arterial blood gas (ABG), showed pO2 53 mmHg on room air (FO2 21%), and pO2 58 mmHg after administration of pure oxygen (fO2 100%), which suggested the presence of a severe shunt. Familial history was positive for valvular heart diseases; Past history was positive for surgery valvulotomy on a stenotic pulmonary valve at 8 years of age; hospitalization in 2006 for acute dyspnea and polypnea associated to severe back-pain. Physical examination was normal. Laboratory tests showed polyglobulia (Hb 18 g/l) Consequently diagnostic hypotheses were for cardiac or pulmonary shunts In the Diagnostic work-up we performed the following diagnostic tests: Chest X-ray: accentuation of vascular pattern. Chest Angio-CT: aneurysm of pulmonary artery (diameter: 50 mm) with dilatation of both right and left branch without evidence of endoluminal images related to thromboembolism, extracardiac vascular shunt and arteriovenous fistula. Trans-esophageal echocardiogram: right ventricular dilatation, intra atrial septum defect with a bidirectional shunt (mainly left to right), pulmonary valve insufficiency.

A 62-year-old man, on polypharmacy treatment for depression and anxiety, presented to our department in April 2009 complaining of dysphagia, fatigue, palpitation, and sweating, which had begun one month earlier. He had also lost 18 kg of body weight over the last 3 years. The previous medical history was unremarkable. Before hospital admission, he had undergone computed tomography (CT) of the brain, upper gastrointestinal endoscopy and abdominal ultrasonography, the latter two showing signs of chronic esophagitis associated with hiatal hernia and gallstones, respectively. On physical examination, the patient appeared confused, although capable of understanding and carrying out tasks. Blood pressure was 145/90 mm/Hg, heart rate 135/min, oxygen saturation by pulsoxymetry 95% while breathing room air. The oral mucosa was dry. Neurologic examination demonstrated difficulty in opening the mouth and sticking the tongue out, rhinolalia, dysarthria with sialorrhea, and dysphagia with regurgitation of food into the upper airways. Serum levels of fT3 and fT4 were increased (fT3 12,74 ng/L, fT4 43,30 ng/ L), and TSH was suppressed (0,008 mIU/L). Hypernatremia (170 mEq/L) with slightly increased concentrations of urea and uric acid with normal potassium values was also found. Thyroid scintigraphy showed diffusely increased uptake of the radioligand, consistent with Graves-Basedow disease. TSH receptor antibodies were positive at high titres (13,90 U/L). Treatment with tiamazol and propanolol, along with intravenous fluids, rapidily normalized the heart rate and sodium serum levels. Nevertheless, the patient’s neurologic symptoms persisted. MRI of the brain was negative. Electromyography demonstrated alterations partially, but not conclusively consistent with a disease of the neuromuscular junction. Since a transient improvement of the picture was observed after the administration of edrophonium, pyridostigmine and prednisone were started. The patient recovered, and eventually was discharged. CT of the thorax excluded the presence of any thymic lesion. Antibodies neither to the acetylcholine receptor (AChR) nor to the muscle specific receptor tyrosine kinase (MuSK) were detected. Two months after discharge from the hospital, while well being the patient suddenly suffered from weakness of the muscles of the neck,

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up to not being able of keeping the head upright. Therefore, eight cycles of plasmapheresis were performed in addition to pyridostigmine, prednisone, and tiamazol. The patient then did well for a whole year. Prednisone was stopped, and pyridostigmine progressively tapered down because of nausea and bradycardia. In April 2011, two years after the clinical presentation, pyridostigmine was also suspended. The patient is currently on 2.5 mg of tiamazol per day; he is asymptomatic and lives a normal life. The present case raises some issues about the complexity of the differential diagnosis of muscle weakness and altered consciousness occurring along with uncontrolled hyperthyroidism. Thyrotoxicosis can cause myopathy by itself. Neurologic symptoms in a patient with autoimmune thyroid diseases (AITD) should always prompt the suspicion of Hashimoto encephalitis. Periodic paralysis should be considered too, if serum potassium is low. Finally, AITD can be associated with myasthenia gravis in the context of autoimmune polyendocrine syndrome type 3.

We decided to investigate endoscopically the lung lesions. Histological examination showed ‘‘intraalveolar extravasation bleeding with neutrophilic granulocyte infiltration of the septum, consistent with inflammation of the capillaries as per Wegener’s granulomatosis’’. Therefore, the patient was treated with cyclophosphamide [1] 750 mg/m2 one bolus per month for six months and methylprednisolone 0,5 mg/Kg/day. The patient was followed-up each month with evidence of progressive clinical improvement and decrease of 24 h proteinuria. After six months, lung lesions were still present on CT scan, so we maintained cyclophosphamide (four more infusions, one every two months) tapering steroid dosage down to 6,25 mg/day, with sustained clinical-laboratory remission and absence of disease relapse until now. Reference 1. Villa-Forte A. European League Against Rheumatism/European Vasculitis Study Group recommendations for the management of vasculitis. Curr Opin Rheum 2010;22:49-53

Atypical presentation of a small vessel vasculitis E. Bracci, L. Paolini, B. Gabrielli, M.G. Danieli, G. Moroncini, A. Gabrielli

The celiac iceberg

Istituto di Clinica Medica, Dipartimento di Scienze Mediche e Chirurgiche, Universita` Politecnica delle Marche, Ancona, Italy

L. Castorani, S. Pugliese, G. Palasciano

L.T., a 69 year old caucasian woman, came to our observation because of intermittent fever started with thrill, widespread arthromyalgias with functional limitation, asthenia, dermographism, anorexia and about 6 kg weight loss in the last 5 months. Added to this, a broad erythema appeared about a month before our observation. Laboratory investigations indicated increased inflammatory markers. In the medical history, a uterine polyp was diagnosed four years before and never histologically examined. A previous clinical diagnosis of psoriasis was reported. We made the following diagnostic hypotheses: 1) infectious disease, 2) paraneoplastic syndrome (uterus neoplasm?, lymphoid disorder?), 3) systemic autoimmune disorder (vasculitis?, Still disease?).

HYPOTHESES CONFIRMATIONS

EXCLUSIONS

Infectious disease

Hyperpyrexia with thrill, neutrophilic leukocytosis

Negative cultures and microbiological tests, echocardiogram without valve vegetations, no response to broadspectrum antibiotic therapy

Paraneoplastic syndrome

Weight loss, arthromyialgias, Absence of Bence-Jones proteinuria dermographism,high levels of LDH and enlarged lymph nodes or other e b2-microglobulin solid lesions on chest and abdomen CT scan, no abnormalities of bone marrow biopsy. Unchanged uterine lesion compared to previous controls, in uterine fibromatosis.

Systemic

autoimmune disorder

Negative

immunological serology, presence of leukocytoclastic vasculitis on skin biopsy, absence of vasculitislike skin lesions and upper airway inflammation, no response to corticosteroid therapy.

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Erythema and dermographism, arthromyalgias, increase of markers of inflammation, proteinuria and microalbuminuria, bilateral pulmonary ground-glass consolidations.

Clinica Medica ‘‘A. Murri’’ Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, Bari, Italy C.C., woman, 20 years old, has come to our attention with intense fatigue, weight loss of about four kilograms in two months, diarrhea without blood and mucus. On examination the patient has shown pallor of the skin and mucous membranes, hypotension (blood pressure: 90/70 mmHg). Assessing the heart, lungs and abdomen have not revealed any pathology. The first biochemical investigations have revealed iron deficiency (serum iron: 16 ug/dl with normal values between 35 and 150 ug/dl), ferritin: 2.77 ng/ml (with normal values between 9 and 81 ng/ml), hypoproteinemia (6.1 g/dl with normal value between 6.4 and 8.2 g/dl), hypoalbuminemia (3 g/dl with normal value between 3.4 and 5 g/dl), cholesterol-lowering HDL (24 mg/dl with normal value [ 35 mg/dl) and serum protein electrophoresis increase in fractions a1, a2 and b1. The patient has reported to have been hospitalized five years before and one year earlier in another hospital for the same gastrointestinal symptoms and was discharged with the following diagnosis: ‘‘pseudo appendicular colic’’ and ‘‘enterocolitis and iron deficiency anemia’’. She has also said to be a beta minor thalassemia carrier. Given the clinical presentation and the results of the first examination and anamnesis, we had hypothesized that it may consist of: 1) malabsorption (celiac disease) 2) inflammatory bowel disease (Crohn’s disease) 3) acute gastroenteritis 4) thyroid disease (hyperthyroidism). Therefore we have decided to carry on other investigations: determination of serum immunoglobulins, IgA (AGA IgA) and IgG antibodies to gliadin (AGA IgG), IgA antibodies to endomysium (EMA), anti transglutaminase antibodies IgA (t-TG IgA) and IgG (t-TG IgG), thyroid function complete with autoantibodies, coproculture, parasitological examination of stool, Widal Wright serodiagnosis. We have found positive anti-transglutaminase antibodies IgA ([ 200 u/mL), antitransglutaminase antibodies IgG (30.1 U/ml), IgG antibodies to gliadin ([ 400 U/ml), IgA antibodies to gliadin, IgA antibodies to endomysium. We have diagnosed a subclinical hypothyroidism with TSH 4.13 mIU/l (normal range between 0.3 and 3.6) and normal thyroid fractions. The positivity for antibodies for celiac disease has led us to investigate the HLA histocompatibility complex and sub-

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sequently to perform a gastroscopy with biopsies of the first and second portion of the duodenum. The patient has the HLA DQ2 heterodimer; endoscopy has shown the typical macroscopic features of celiac duodenum: mosaic duodenal mucosal pattern and scalloping of Kerkring folds. Histological examination of duodenal biopsy has shown significant inflammatory lymphoplasmacytic infiltrate with increased intraepithelial lymphocytes and villous atrophy, so it is compatible with celiac disease 3c according to the histological classification of Marsh-Oberhuber. We have dismissed the patient with the diagnosis of ‘‘celiac disease, iron deficiency anemia, subclinical hypothyroidism’’. The recommended treatment is: 1 tablet levothyroxine 25 mcg/day, ferrous sulfate 1 cp/day for 21 days and glutenfree diet.

After formulating the diagnosis of Hashimoto thyroiditis, we prescribed the patient therapy with levo-thyroxine, reaching a therapeutic dose of 50 lg/day. After four months, we observe the normalization of the exams: fT3 3.9 pg/mL, fT4 1.52 ng/dL, TSH 0.24 mUI/L, RBC 5.17 9 1012/L, Hb 14.4 g/dL, MCV 88 fL. The patient was completely asymptomatic. We was referred by us to a Universitary Clinic. The Hashimoto thyroiditis is a very common autoimmune condition, especially common in female sex; it is a systemic disease, known to affect the hemopoiesis, the whole body metabolism, the function of the liver, of the kidneys and of the muscles. In this case, the value of TSH at diagnosis was exceptionally high, and that is not so common; besides, both the symptoms and the alteration of the laboratory tests had a rapid onset. The Hashimoto thyroiditis seemed ‘‘a posteriori’’ to be the cause of the symptoms.

Hashimoto thyroiditis: a systemic disease

References 1. Pearce EN, Farwell AP, Bravermann MD. Thyroiditis. NEJM. 2003;348:2646-55 2. Das KC et al. Erythropoiesis and erythropoietin in hypo- and hyperthyroidism. J Clin Endocrinol Metab. 1975;40: 211-20 3. Kreisman SH, Hennessey JV. Consistent reversible elevations of serum creatinine levels in severe hypothyroidism. Arch Intern Med. 1999;159:79-82

M. Cecchetto, A. Faedo, A. Fornasiero, P.L. Pujatti U.O.C. Medicina, Ospedale di Arzignano (VI), Italy We report the case of a 26 year old man complaining of asthenia, diffuse myalgias, muscle rigidity from months; he also reported constipation. In April 2010, the routine laboratory tests showed normochromic normocytic anemia (Hb 10.4 g/dL, RBC 3220 9 1012/L, MCV 89 fL), renal failure (creatinine 1.50 mg/dL), alteration of liver enzymes (AST 243 U/L, ALT 297 U/L), elevation of LDH (1190 U/L) and of CPK (2288 U/L). Eight months before, during pre-operative exams for minor orthopedic surgery, very mild alterations of hemochrome, renal and liver function were considered as due to heavy use of nonsteroidal anti-inflammatory drugs (NSAIDs) We first visited him as an outpatient. At the time, the patient was not taking NSAIDs anymore; he was not taking any drugs, nor alcohol, he was neither addicted to cigarette smoking nor to intravenous drugs (he reported previous use of heroin for a short period). The patient was admitted to our Medical Department. The physical exam showed a mild oedema of the legs and a slight thickness of the skin of the face. The routine laboratory tests confirm the anemia, the renal failure, the alterations of liver enzymes, the elevation of LDH and CPK; we also documented dyslipidemia (triglycerides 251 mg/dL, total cholesterol 349 mg/dL), serum albumin 5.9 g/L, PT-INR 1.12, PTT ratio 1.14, fibrinogen 178 mg/dL. A chronic blood loss, especially due to NSAIDs abuse, was excluded when performing the hemoccult and the iron profile. The dosage of erythropoietin was 12.2 mU/mL (with normal values of 1.6-34.0 mU/ mL), the dosage of B12 and folic acid was in the range of normality. The Coombs test, the haemoglobin electrophoresis, the erythrocyte sedimentation rate, the C reactive protein were normal, the antitransglutaminase antibodies tested negative. Rheumatoid arthritis was excluded both on serological and clinic diagnostic criteria. The abdomen ultrasonography did not showed alterations. We also performed serologic tests for HBV, HCV, Toxoplasma, CMV, Mycobacterium tuberculosis, Treponema pallidum, especially because of the liver dysfunction. The thyroid function tests, performed twice, showed a marked autoimmune hypothyroidism: fT3 \ 0.03 pg/mL, fT4 0.05 ng/dL, TSH 438.30 mUI/L, anti-thyroglobulin antibodies 2993 UI/mL, anti-thyroperoxydase antibodies [ 600 UI/mL, thyroglobulin \ 0.1 lg/L. We then perform the thyroid ultrasonography, which disclose a diffuse dishomogeneous and hypoechogenous pattern, and the bone marrow biopsy, which reveal a poor cellularity (less than 10%).

Atrial myxoma: a clinical case M. Cecchetto, M. Galiotto, C.S. Checchetto, A. Vergolani, P.L. Pujatti U.O.C. Medicina, Ospedale di Arzignano (VI), Italy We report the case of a 55 year old woman, presenting with a 2-yearhistory of asthenia, slight fever, cardiopalmus, diffuse arthromyalgia, diarrhoea and weight loss of about 6 kg. She any medical or surgical problem in the past. She was not taking drugs, except for loperamide when necessary. In July 2008 the patient first came to the First Aid of our Hospital complaining of cardiopalmus, without anger or dyspnea. The physical examination and the ECG did not disclose significant alterations. The laboratory tests only show a mild anemia, of new onset: RBC 3.76 9 1012/L, Hb 10.4 g/dL, Ht 32.3%, MCV 85.9 fL. In order to better understand the cause of the anemia and of the others symptoms, the patient underwent a series of biochemical and instrumental tests, in several hospitals. The laboratory tests only showed a mild elevation of the erythrocyte sedimentation rate (ESR 41 mm/h) and C reactive protein (C-RP 38 mg/dL), while thyroid function, dosage of erythropoietin and homocysteine, haemoglobin electrophoresis were normal; hemoccult, gastric parietal cell antibodies, ANA, ENA, rheumatoid factor, AMA, ASMA, ANCA tested negative. The EGDS, the pancolonscopy, the abdomen and thyroid ultrasonography, the chest radiography, the orthopantomography did not reveal a cause of the anemia nor of the inflammation. The bone marrow biopsy showed normal cellularity, augmented erythroid component, rare siderophages; the pattern, according to the Hematologist, was typical of anaemia of chronic disease. In August 2010, the patient was visited by our Rheumatologist, who noticed that the increase of ESR and C-RP followed and not preceded the anemia, the polymyalgia rheumatica being so probably excluded in differential diagnosis. Nevertheless, he prescribed prednisone to the patient, without benefit, and he then prescribed a PET-CT, which tested negative. The patient was then admitted to our Medical Department in November 2010.

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S212 The physical examination did not disclose any alterations. At the laboratory tests: RBC 3.96 9 1012/dL, Hb 9.4 g/dL, MCV 77.8 fL, reticulocytes 0.033 9 1012/dL, C-RP 47 mg/L, ESR 41 mm/h, fibrinogen 431 mg/dL, elevation of a2globulins and of acid a1glicoprotein (1.8 lg/dL), iron 18 lg/dL, ferritin 131 lg/L, transferrin 2.5 g/dL; we also excluded hemolysis. Cryoglobulins, hemocultures, urinocultures, coprocultures, serological tests for CMV, EBV, toxoplasma, parvovirus B19, Borrellia, Salmonella were also performed to exclude causes of combined anemia, fever and arthromyalgias. We repeated the EGDS and the biopsy of the duodenum showed a mild alteration of the crypt to villous ratio, with augmented intraepithelial lymphocytes. The anti-transglutaminase antibodies tested negative. We will repeat the exam in the next months, because the patient was following a gluten-free diet at the time. She also complained of cardiopalmus. The dynamic ECG was diagnostic of supraventricular and ventricular extrasystolia, without a typical pattern. Both the transthoracic and transesophageal echocardiography showed a 6-cm mass on the anterior mitralic leaflet, floating in the left atrium, determining a functional mitralic stenosis during diastole and thus partially explaining the cardiopalmus. The patient underwent a cardiosurgical procedure of asportation of the mass and reconstruction of the atrial septum with a bovine pericardium patch. The histologic exam was diagnostic of atrial myxoma. The post-operative recovery was regular. In April 2011, the patient was completely asymptomatic; the hemochrome, the ESR and the C-RP test normal. The atrial myxoma is a rare but known cause of anaemia, also with a flogistic mechanism. Cytokines and interleukins elevation is seen in this benign tumour, and this seems to be the cause of the anemia and of most of the other symptoms of the patient in this case. References 1. Weiss G, Goodnough LT. Anemia of Chronic Disease. NEJM. 2005;352:1011-23 2. Mendoza CE, Rosado MF, Bernal L. The role of interleukin-6 in case of cardiac myxoma. Clinical features, immunologic abnormalities, and a possible role in recurrence. Tex Hearth Inst J. 2001;28:3-7

A rare case of catastrophic SIRS E. Cistaro1, G. Lupattelli1, R. Brugnano2, O. Minelli3, A. Elmo1, P. Rondelli1, G. Oliverio1, E. Mannarino1 1 Dipartimento di Medicina Clinica e Sperimentale, Universita` degli Studi di Perugia; 2Nefrologia; 3Servizio Immunotrasfusionale, Osp. S. Maria della Misericordia Perugia, Italy

A forty years old woman was admitted to the Department of Internal Medicine for fever and arthralgia since ten days; two months before she had an erisypela on right leg treated with amoxicillin-clavulanate. At the admission physical examination revealed a suffering patient, respiratory rate 28 min, blood pressure 118/80 mmHg, heart rate 120 bpm, sat O2 85%, temperature 38.5C, diffuse ecchimotic lesions on arms and livedo reticularis on legs. A reduction of bibasal vescicolar murmur was present at lung examination, heart, abdomen, and neurological examinations were normal. At hemogasanalysis respiratory alcalosis and hypoxiemia; blood chemistry showed increased C-reactive protein, normocitic anemia, with high ferritin values, positive direct Coombs, neutrophil leucocytosis, thrombocytopenia, increased hepatic enzyme, prolonged partial tromboplastin time, reduced prothrombin time and reduced creatinine clearance, with ialine casts and proteinuria at urine examination. Two blood culture specimens were positive for Staphylococcus hominis with increased procalcitonin, values consistent with sepsis. Chest X ray and echocardiography showed pleural and pericardial effusions. Abdomen CT

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 scan showed the presence of monolateral adrenal glan haemorrhage and a complicated (infectious?) renal cyst. NMR of the brain showed the presence of a recent ischemic lesion of the white matter near the fourth ventricle. Actually, ten years before she had a diagnosis of antiphospholipid syndrome (APS), due to poliabortivity and positive anticardiolipin antibodies; she was not on anticoagulation. Autoimmunity pattern revealed the presence of antinuclear antibodies, anti DNA, anti cardiolipin (pattern IgG) anti b2-glycoprotein and lupus anticoagulant (LAC). At presentation this case was as a systemic inflammatory response syndrome (SIRS) with multi organ involvement (hematological, adrenal, neurological, renal, hepatic, skin and serositis). The differential diagnosis could be consistent with sepsis and disseminated intravascular coagulation (DIC) in a patient with APS or systemic lupus erythematosus (SLE); alternatively it could be also a catastrophic antiphospholipid syndrome (CAPS). The patient satisfied six out of the eleven criteria for the diagnosis of SLE (1) and sepsis with DIC could not be excluded due to positive blood culture, increased procalcitonin, complicated renal cyst and hemorrhagic/ thrombotic complications. But some elements were more consistent with the diagnosis of CAPS, or Asherson’s syndrome: the occurrence of SIRS, the involvement of more than three organs in an extremely rapid progression (one-two weeks), the involvement of unusual organ such as adrenal gland with positive LAC and anticardiolipin antibody (2). Another characteristic feature of CAPS was the ‘‘trigger’’ of the disease, in this case infection and lupus flare, in a patient where the primary APS had been silent for ten years. The patient was treated with high dose methylprednisolone, immunoglobulins and daily plasmapheresis; due to the presence of the renal cyst with positive blood cultures, she was also treated with tigecycline, vancomycin, ceftriaxone, meropenem. Cyclophosphamide was administered although the presence of infection. Because of adrenal haemorrhage anticoagulation therapy could not be started, just leaving enoxaparin prophylactic. In the following weeks renal function worsened with the need of hemodialysis; she also developed a cardiac tamponade due to intrapericardial haemorrhage, treated with pericardiocentesis. After two months neurological involvement became more severe, with recurrent epilepsy and psicosis. Three months after the admission the patient died. CAPS is an extremely rare disease, representing less than 1% of the APS cases: in the ‘‘CAPS registry’’ only 284 cases are recorded since 1984 (3); it is characterized by a high mortality, despite aggressive and early therapy. References 1. American College of Rheumatology. Arthritis and rheumatism. 1999;42:1785 2. Asherson RA. Lupus. 2003;12:530 3. http://www.med.ub.es/MIMMUN/FORUM/REGISTRY2.HTM

A case of fever with severe neutropenia F. Costanzo, D. Grataroli, M. Masotti, R. Invernizzi, G. Bergamaschi, G.R. Corazza Clinica Medica I e Clinica Medica III, Universita` degli Studi di Pavia e IRCCS Policlinico San Matteo di Pavia, Pavia, Italy An 81-year-old woman was seen at the Emergency Department of our Institution because of an 8-day history of fever, up to 39 C, and chills, unresponsive to empiric antibiotic therapy with amoxicillin/ clavulanate. Blood tests showed severe leukopenia (0.85x109/L) with 2% neutrophils, in the absence of thrombocytopenia or anemia; the chest radiograph was negative for pneumonia.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 In the past the patient underwent surgical procedures for umbilical and inguinal hernioplasty, appendectomy, hysterectomy for genital bleeding, and cataract. Stage IV renal failure was present (creatinine = 1.45 mg/dl at last determination). In 1986 a stenotic aortic valve, secondary to rheumatic disease, was replaced with a mechanical prosthesis; five years before the present admission a surgical procedure for a descending aorta aneurysm and a single coronary artery bypass graft were performed. The latter was followed by development of chronic heart failure. A recent admission to a Department of Internal Medicine because of reacutization of congestive heart failure is reported. The patient’s conditions improved following parenteral diuretic therapy. On discharge, allopurinol was added to standard therapy for heart failure ischemic heart disease, given the presence of moderately increased uric acid levels (\ 10 mg/dl). On admission serial blood and urine cultures were performed; treatment with antibiotics (ceftriaxone and levofloxacin) and itraconazole was started; home therapy was confirmed, with the exception of allopurinol. On the second day a peripheral blood smear and bone marrow examination were performed (confirming absolute peripheral blood neutropenia, associated with reduced bone marrow cellularity, normal relative representation of myeloid precursors in the absence of an increased number of blasts), followed by therapy with granulocyte-colony stimulating factor (G-CSF, filgrastim 300 mcg/day). Fever quickly resolved and, within the fourth hospital day, leukocyte counts increased to 11 9 109/L, with 88% neutrophils. G-CSF was discontinued. On the sixth day antibiotics and itraconazole were discontinued too. The patient was discharged with the diagnosis of agranulocytosis probably induced by treatment with allopurinol. In the reported patient the introduction of a new drug to treat a biochemical alteration, that was not causing symptoms, lead to the development of a potentially fatal side effect. We present this case report to emphasize the need for the accurate evaluation of the risk/ benefit ratio associated to the use of several drugs to treat patients with multiple pathological conditions. These are often elderly patients who more frequently develop side effects.

S213 Hypothesis: Cancer (hematologic or solid?), Autoimmune disease (connectivity?), Infection (with organ or systemic localization?). Laboratory tests: Routine blood tests, including white blood cells, liver and kidney panels, electrolytes and urinalysis are normal, except for elevated erythrocyte sedimentation rate that is 58, PCR 11,700, Urine culture: negative, Blood cultures: No. 5 all negative, VIDAL-WRIGHT: negative, HEPATITIS MARKERS: negative, TORCH: negative for acute infections, HIV negative, ANTI Chlamydia Ab: negative, IgA 290, IgG 1620, IgM 108, ANA: doubt, Rheumatoid factor: 43, Waaler-Rose positive, alpha-1 glycoprotein: 191, QSP: albumin 4:33, alpha1 0.17, alpha2 1.02, beta 0.85, gamma 1.13. Instrumental tests: ECG, chest X-ray, echocardiography: normal. Abdominal ultrasound: mild splenomegaly (d = 14.8 cm). Lymph node ultrasound: in left inguinal region presence of a hypoechoic dishomogeneous 28.2 9 18.2 mm nodule with polycyclic margins and richly vascularized, to probably relate to a lymph node package. Nothing to evidence on the other side. Presence of enlarged lymph node in aorto-caval area. Course: During the first 7 days, the patient continues to have fever spikes up to 40 C, episodes of abdominal pain, severe asthenia and discomfort. The results do not confirm the initial assumptions, it remains strong the hypothesis of a tumor and/or infectious disease, although there are some elements (ANA, QSP, VES, aphonia, etc.) that confound the diagnostic iter. Other tests: 2 Vidal-Wright test: neg.; 6 blood culture: neg., a bone marrow aspiration biopsies to search for the parasite was programmed, Total Body CT for malignant lesions: fatty liver, pancreatic calcifications and cysts, inguinal lymph node with dishomogeneous c.e. after contrast, mesenteric lymph nodes \ 1 cm. Inguinal lymph node biopsy for confirmation/exclusion of metastasis or lymphoma: lymph node tissue, histomorphological and architectural disruption typical of poorly differentiated malignant neoplasia of probable epithelial origin (carcinoma). Diagnosis: epithelial neoplasia of unknown origin. Other tests performed for the research of the primary tumor and the exclusion or the confirm of infectious/parasitic origin of the fever:

Strategic diagnosis: a case report O. Cuccurullo1, D. Padula2, G. Musca1 Division of Internal Medicine, Cetraro, A.S.P. Cosenza, Italy; 21st Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy

1

A 67-year-old man is admitted to hospital for remitting-intermittent fever (39.5C max), preceded by shaking chills, with profuse sweating during defervescence, that persisted among 20 days; diffuse osteo myalgias are also present. He refers in the last four months weakness and weight loss (8 kg). Unspecified antibiotics and steroids (for 6 days) had no effect on any of the symptoms. History: heavy drinker and smoker, moderate consumer of cheese, constipated bowel function. In the last years he reports pain in small joints, sporadic episodes of aphonia; the onset of a left inguinal not painful swelling. Hypertension treated with ACE-I. His past medical history included: 6/2006: chronic pancreatitis and pancreatic pseudocysts, 5/2007: obstructive pancreatitis and suspected cefalo-pancreatic cancer (histology not available), jejunum pancreatic anastomosis and cholecystectomy; after surgery follow-up in July 2007: alimentary diet and enzyme replacement therapy. Healthness in the last 3 years. Physical examination: pallor, bad general conditions, dehydration, hepatosplenomegaly, inguinal lymph node are the size of a walnut, hard, not painful, mobile under the skin but fixed to the underlying tissue.

– Colonoscopy: sessile polypoid formation localized in the ascending colon (tubular adenoma of the large intestine with an outbreak of high-grade epithelial dysplasia (moderate); – Urogenital Tests (Clinical, laboratory and instrumental): all negative. – Fine-needle aspiration of bone marrow : Mild hyperplasia of the granulocytic series. Presence of some plasma cells. Presence of amastigotes. Final diagnosis: VISCERAL LEISHMANIA - EPITHELIAL CANCER OF UNKNOWN ORIGIN Therapy and course: Ambisone cycle for 28 days. From the second day the fever get resolved with gradual improvement of the general status. One month later : good general conditions, asymptomatic, weight gain of 4 kg. PET is negative. However, the oncologist decides to carry out non-specific chemotherapy. Conclusions: The case evidences four important concepts: – Presence of systemic symptoms and signs, involving various diseases, in a framework of complexity and nonlinearity. – Need for differential diagnosis – Importance of ‘‘distractor’’ elements (clinical, laboratory and instrumental) that contrast the most probably hypothesis pushing to a reasoned so strategic differential diagnosis. The importance of the decision making: to subject the patient to chemotherapy?

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S214 Gitelman’s Syndrome in a 72 years old man: clinical case report G. De Benedetto; A. Bellomo; B. Marigliano; C. Fossati; V. Marigliano Dipartimento Scienze Cardiovascolari, Respiratore, Nefrologiche e Geriatriche, Universita` Sapienza, Roma, Italy A man aged 72 years old who had been reporting episodes of generalized weakness with recurrent cramps for the past 25 years came to our attention five months ago. The weakness, which got worse after exercise and a high-fat meal, affected the proximal limb muscles. Every episode lasted few hours. The only symptoms between attacks were polyuria and nicturia. There was not vomiting nor diarrhoea. The patient was not taking any medications. Family history appeared to be negative for other similar episodes. On physical examination, performed during a crisis, we found out a flaccid quadriparesis. No other muscles were involved. Blood pressure was normal. Serum potassium was persistently low even between the attacks (1.4 mmol/L). An excessive loss of potassium, chloride and magnesium was detected in the alkaline urine (potassium 300 mmol/24 h, chloride 658 mmol/24 h, magnesium 52 mmol/24 h). The patient also had hypomagnesaemia, hypochloraemia, and metabolic alchalosis (Magnesium 0.4 mmol/L, chloride 89 mmol/L, bicarbonate 33 mmol/L, blood pH 7.38). The urinary calcium excretion was subnormal at 1.0 mmol/24 h. Serum calcium was 2.5 mmol/L, Sodium 138 mmol/L. FT3, FT4, TSH were normal. Hypomagnesaemia responded to oral supplementations, while hypokalaemia seemed to be persistent despite high doses of parenteral potassium. The patient refused to undergo any genetic test to detect a gene mutation, but we suspected a diagnosis of Gitelman’s Syndrome (GS). Oral Indomethacin 25 mg three times a day was then empirically started. He is still symptoms free and normokalaemic after five months of follow up. Episodic weakness beginning after the age of 25 years old is almost due to primary periodic paralysis [1]. Further, low serum potassium between attacks and absence of similar family history should raise strong suspicion of a secondary disorder [2]. Secondary hypokalemic periodic paralysis with normotension, alkaline urine and metabolic alkalosis is usually seen in hyperplasia of the juxtaglomerular apparatus with hyperaldosteronism [2, 3]. Also known as Bartter’s Syndrome (BS), this condition begins in childhood with clinical signs as short stature, polyuria, polydipsia and a tendency to dehydratation during infancy or before school age. Classic BS is a severe congenital disease that is necessarily recognized before the age of 6 years. GS is a milder variant of BS with a later presentation. It also differs from BS in being associated with hypocalciuria [4]. Renal magnesium wasting is found out in all patients with GS and in about one third of those with BS. Tetany may be due to exacerbation of alkalosis and consequent low ionized plasma calcium in presence of hypomagnesaemia. Usually the underlying condition is obvious, but recurrent episodes of transient weakness can sometimes be difficult to distinguish from primary hypokalaemic periodic paralysis. The paroxysmal nature of the attacks is unexplained and it is not known whether the ionic shifts during the attacks are the same as in the primary hypokalaemic form. The timing of the attacks may relate to the fluctuations in catecholamine levels and the consequent regulation of sodium potassium ATPase function [2]. Insulin causes entrance of potassium into cells which may account for the precipitation of paralysis by large carbohydrates meals. The laboratory characteristics of GS may be mimicked by treatment with diuretics, particularly thiazides, which inhibit the luminal sodio-chloride cotrasporter in the distal convolute tubule. The clinical features of BS and possibly also GS are to a large extent caused by raised levels of prostaglandins. These compounds stimulate renin secretion thereby promoting potassium wasting by direct action and through stimulation of natriuresis. They also have a direct effect on aldosterone biosynthesis. Indometacin is usually used to treat both syndromes, but especially

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 BS for its beneficial effect of inhibiting the synthesis of prostaglandins [5]. References 1. Mendell JR, Griggs RC, Ptacek LJ. Disease of muscle. In: Fauci AS, Braunwald E, Isselbacker KJ et al., editors. Harrison’s Principles of Internal Medicine, 14th edn. New York: McGraw-Hill; 1998. pp 2473-85 2. Moxley RT. Metabolic and endocrine myopathies. In: Walton J, Karpati G, Hilton-Jones D, editors. Disorders of voluntary muscle, 6th edn. New York: Churchill Livingstone; 1994. pp 647-716 3. Rose M, Griggs R. Inherited muscle, neuromuscular, and neuronal disorders. In: Goetz CG, Pappert EJ, editors. Textbook of Clinical Neurology. Philadelphia: WB Saunders; 1999 pp 719-30 4. Bettinelli A, Bianchetti MG, Girardin E et al. Use of calcium excretion values to distinguish two forms of primary renal tubular hypokalemic alkalosis: Bartter and Gitelman Syndromes. J Pediatr. 1992;120:38-43 5. Kleta R, Basoglu C, Kuwert-Broking E. New treatments options for Bartter’s Syndrome. N Engl J Med. 2000;343:661

A common virosis as a trigger of a rare disease S. De Vuono1, G. Lupattelli1, M. Marchesi2, A. Elmo1, L. Callarelli1, E. Mannarino1 1 Dipartimento di Medicina Clinica e Sperimentale, Universita` degli Studi di Perugia, Perugia, Italy; 2Servizio Immunotrasfusionale, Osp. S. Maria della Misericordia, Perugia, Italy

A 33-year-old woman was admitted to our Department because of intermittent fever, jaundice and hyperchromic urine. On physical examination the patient was eupnoic, pyretic (38,5C), with jaundice, blood pressure 120/78 mmHg, heart rate 70 beats/min. There were not hepatomegaly, splenomegaly or superficial lymphadenomegalies. Abdomen, heart and lung examinations were otherwise negative. The patient reported a ‘‘flu-like syndrome’’ (malaise, asthenia, slight fever and rhinorrhea) about two weeks before, treated with amoxicillin/ clavulanic acid for seven days. She had a travel in Venezuela in malaric areas four months earlier. She reported no smoke, no use of alcohol or illicit drugs and the remaining clinical history was unremarkable. The main differential diagnosis included acute obstructive jaundice, hemolytic anemia and malaria. Initial laboratory tests showed: elevated VES and CRP, severe normocytic anemia (Hb 6 g/dl) with normal reticulocytes count, leukocytosis with neutrophilia, hyperbilirubinemia (11.1 mg/dl) almost all indirect, elevated SGOT with normal SGPT, elevated LDH, reduced haptoglobin and increased procalcitonin levels. Leukocytosis and elevated procalcitonin levels could be consistent with a bile tract infection, but the negative abdomen examination and the indirect hyperbilirubinemia were inconsistent with this hypothesis, which was definitively excluded with an abdomen ultrasonography. On the other side the contemporary presence of anemia, indirect hyperbilirubinemia, elevated LDH and consumed haptoglobin was highly suggestive of intravascular hemolysis, even though a normal reticulocyte count. Thick and thin blood smears for malaria diagnosis were both negative. Peripheral blood smear and osmotic globular resistence were performed and excluded the presence of spherocytosis, while the direct antiglobulin test (DAT or Coombs test) was highly positive (++++), only anti-C3 positive and anti-IgG negative. In this case a positive DAT could be due to an autoimmune hemolytic anemia (warm autoimmune hemolytic anemia, cold agglutinin syndrome, paroxysmal cold hemoglobinuria, or a mixed type) or to a drug-induced hemolytic anemia. The latter hypothesis could be excluded for three reasons: no strict temporal criteria, previous use of amoxicillin without any adverse event, Coombs IgG negative. Antibodies at 4, 20 e 37 were negative.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Thus, biphasic haemolysin (Donath Landsteiner antibody) was tested and it was highly positive: on these findings a diagnosis of paroxysmal cold hemoglobinuria (PCH) was made. PCH is historically associated with congenital or late stage of syphilis, but VDRL test was negative. It must be considered that PCH could be associated with other pathologies, including malignancy, lymphomas, autoimmune disorders and infections, particularly viral infections. Chest x-ray, abdomen ultrasonography, total body CT and neoplastic markers did not find any malignancy. The absence of superficial lymphonodes, peripheral lymphocyte immunophenotype and the negative CT scan excluded lymphomas. Serological screening for autoimmune disorders was negative. Pharyngeal tampon was negative for bacteria, Adenovirus, Influenza and Parainfluenza viruses. Urine culture and coproculture, were all negative. IgM antibodies for CMV, HSV-1, HSV-2, EBV, Parvovirus B19, Coxackie viruses, Adenovirus, Chlamydia, Mycoplasma were all negative; HIV and hepatitis A, B and C were negative. Thus the conclusive diagnosis was paroxysmal cold hemoglobinuria associated with an undefined upper respiratory virosis There are not well defined guidelines for PCH treatment, because of the rarity of the disease. Acute PCH characteristically resolves spontaneously from few days to several weeks after the onset and it is rarely a cause of severe chronic anemia or death. Thus treatment of PCH mainly consists of keeping patient warm and, if necessary blood transfusions. Nevertheless corticosteroids or immunosuppressive drugs or plasmapheresis could be used in critical situations: our patient was treated with three methylprednisolone bolus followed by prednisone then gradually tapered off. After two weeks Hb levels increased and intravascular hemolysis signs disappeared, except for positive DAT. A months later Hb was nearly in the normal range, hemolysis signs showed only a reduced haptoglobin. There are at least three peculiar aspects of this case. The first is rarity of this disease, especially in the adult; the second is the suggestion to look for the biphasic hemolysin in case of DAT anti C3 positive and anti IgG negative. Finally the significance of reticulocyte count: in this case the only element inconsistent with a diagnosis of hemolytic anemia was the normal reticulocyte count, usually one of the main feature of autoimmune hemolytic anemia. But PCH is the only autoimmune hemolytic anemia not always characterized by a compensatory increase in reticulocytes, because of the production of antibody against P-antigen, which is expressed on both red blood cells and reticulocytes.

Short bowel syndrome A. Denegri, R. Fornaro Dipartimento di Medicina Interna; Dipartimento di Discipline Chirurgiche, Morfologiche e Metodologie Integrate; Universita` degli Studi di Genova, Genova, Italy The short bowel syndrome is a complex clinical picture that comes after extensive bowel resection and is characterized by diarrhoea, dehydration and weight loss, malabsorption and malnutrition. The extent of resection is not a criterion to predict the onset of short bowel syndrome. Although it is believed that sufficient storage of at least 10% of the length of the small intestine or conservation of the last forty cm and the ileocecal valve for patient survival, residual intestine less than two meters is a condition to develop short bowel syndrome. Ileal resection results in more serious consequences of the jejunal, as the ileum can compensate for jejuna functions. Treatment of patients with short bowel syndrome and its complications is quite challenging. We describe our experience in patients who developed short bowel

S215 syndrome, and medical and surgical procedures that have led to improved quality of life of these patients.

A 47-year-old woman with dyspnea and jaundice F. Di Vece, E. Dalla Nora, G. Zuliani, A. Passaro Sezione di Medicina Interna, Gerontologia e Nutrizione Clinica, Universita` di Ferrara, Ferrara, Italy A 46 yo woman came to the emergency room complaining mild dyspnea, diffuse pain and jaundice onset. The patient referred an accidental fall with a prolonged stay on the wet floor, 2 days before. The patient had a medical history of alcoholism. In the emergency room the patient underwent a Chest X-ray (Diffuse subcutaneous emphysema, uncertain left pneumothorax and XI left rib fracture) and thorax and abdominal CT scan (Diffuse subcutaneous emphysema, pneumomediastinum, and left paramediastinic pneumothorax; right lung contusions signs; fatty liver and hepatomegalia, hydropic gallbladder with thickened wall). The patient was admitted to the surgery department where she underwent fibrobronchoscopy (negative), a single-contrast esophagram (no contrast extravasation) and left chest drain insertion. On the second day the patient was transferred to our ward. At admittance the patient appeared sufferent, agitated, non collaborative and febrile (TC 38C). On examination conjunctivae and skin were icteric. The blood pressure was 110/80 mm Hg, the pulse 100 beats per minute, the abdomen was distended without tenderness; subcutaneous crepitations were evident on the chest, neck and face. There were basilar rales in the left lung field. There was a wide skin lesion on the buttocks, referable to a cold injury. Laboratory tests showed macrocytic anemia (Hb 9.5 g/dl, MCV 105 fl), neutrophilic leukocytosis (WBC 28000/mmc, N 19000/mmc), thrombocytopenia (Ptl 61000/mmc), increased bilirubin (total 22 mg/dl, direct 20 mg/dl), aminotransferase (ALT 106 U/L, AST 154 U/L), ALP 2166 U/L, GGT 2608 U/L and INR (1,54). Testing for hepatitis B, C and A viruses was negative as ANA and AMA screening. Clinical findings suggested a SIRS/sepsis or an acute alcoholic hepatitis. Blood samples for cultures were drawned and ciprofloxacin was administered empirically. A single hemoculture was positive for St. Aureus methicillin Resistant (MetR). Moreover, a culture exam from a purulent drainage of the surgical wound was positive for the same germ. Vancomycin and Ceftazidine i.v. were started on the basis of the antibiogram together with lactilol, parenteral fluid and electrolyte replacement, pantoprazol i.v., canrenoate, ursodeoxycholic acid, vitamin K and B1 supplements and morphine for pain control. Moreover, in order to prevent alcohol withdrawal syndrome, benzodiazepine and Gamma-aminobutyric acid were administered. To support the differential diagnosis of acute alcoholic hepatitis it would have been advisable to perform a liver biopsy however we decided not to proceed, considered the important comorbidities. All prognostic score (MELD = 31, Lille model = 0.99, Maddrey = 51.6, ABIC = 8.2, Glasgow = 10, Child Pugh = 13) were suggestive of a severe alcoholic hepatitis. In these cases guidelines recommend that patients lacking contraindications for steroid use should be considered for a four week course of prednisolone; weaker evidence suggest the use of Pentoxifylline, as a valid alternative. Considering the strong suspicion of an undergoing septic state, we felt pentoxifylline was a better choice. Following clinical course was positive and we assisted to a gradual slow clinical improvement and a progressive reduction of bilirubin

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S216 levels. A CT scan documented a reduction of the subcutaneous emphysema, pneumomediastinum and pneumothorax and on the seventh day chest drain was removed. Few days after the patients started a gradual mobilization and showed a fast recovery of functional autonomy. At discharge hepatic function indexes were only slightly altered (tot Bilirubin 3.0 mg/dl, ALT 19 U/L, GGT 178 U/L, ALP 480 mg/dl, INR1.37). The patient was advised to avoid alcohol and she was discharged with a follow-up appointment at the hepatic outpatient clinic. In conclusion our final diagnosis was an acute alcoholic hepatitis worsened by sepsis sustained from a surgical site infection.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Reference 1. Elliott MA et al. Cancer-associated microangiopathic hemolytic anemia with - thrombocytopenia: an important diagnostic consideration. Eur J Haematol. 2010;85(1):43-50

Diffuse parenchymal infiltrates in a 49 year old woman with Graves’ disease V. Fontana, M. Internullo, L. Borgognoni, A. Russo, P. Marinelli, M. Villiva`, P. Baiocchi, E. Angelici, P. Palange Sapienza Universita` di Roma, Policlinico Umberto I, Dipartimento di Sanita`Pubblica e Malattie Infettive, UOC Medicina Interna I, Roma, Italy

A woman with aphasia, anemia and thrombocytopenia L. Ferrari, G.M. Podda, P. Fracasso, M. Cattaneo Ospedale San Paolo, Milano, Italy A 75 years old woman was admitted to Emergency Room of Ospedale San Paolo of Milano with speech difficulty and weakness in right side of the body. The patient had had a retroperitoneal sarcoma that was treated surgically in 2004 and by radiotherapy and chemotherapy between 2005 and 2008. The follow up computed tomography (CT) scan performed 2 months before the admission, showed a retroperitoneal mass of 9 9 7 cm diameter, infiltrating right ureter and the paravertebral muscles, which was virtually unchanged since the previous control. Medication included paracetamol + codeine. On examination in the emergency department, the patient was awake, aphasic, and unable to recognize her relatives and to carry out simple commands. Her blood pressure was 110/76 mm Hg, pulse rate 104 beats per minute, temperature 36C, respiratory rate 14 breaths per minute, oxygen saturation 97% on ambient air. Her skin was pale; the neurological examination revealed a neurological deficit in the right side of the body. Laboratory tests revealed normocytic anemia (Hb, 6.5 g/dL, MCV, 89 fL), platelet count 90,000/mmc, leukocytosis (WBC 21820/mmc, Neutrophils 84%); serum creatinine, electrolytes, aspartate and alanine aminotransferase and albumin were normal. No sign of acute bleeding was reported. Electrocardiogram, chest radiography and CT of the head without contrast medium were normal. Acetylsalicylic acid (ASA) was administered, because the presence of a cerebral stroke was hypothesized. After the transfusion of 2 units of packed red blood cells, the patient was admitted to the Department of Internal Medicine. Several hypotheses may explain the clinical presentation of the patients: disseminated intravascular coagulation (DIC), catastrophic antiphospholipid syndrome, retroperitoneal bleeding and thrombotic thrombocytopenia purpura (TTP). The presence of microangiopathic hemolysis was revealed by increased serum lactate dehydrogenase (LDH) (1160 U/I), hyperbilirubinemia (1.01 mg/dL), reticulocytosis (153,000/mmc), negative direct antiglobulin test and detection of schistocytes in peripheral blood smear. PT, aPTT and plasma fibrinogen were normal, D-dimer was slightly increased (865 ng/ml), thus ruling out the possibility of overt acute DIC. The patient was critically ill and her mental status deteriorated, but a CT scan ruled out the presence of thrombotic or hemorrhagic stroke. Based on the clinical presentation, the evidence of microangiopathic hemolytic anemia and thrombocytopenia, the presence of TTP was hypothesized. Immunosuppressive treatment with intravenous methylprednisolone (1 mg/kg/ die) and plasma exchange were begun, and ASA was discontinued. After 6 cycles of plasma exchange, her mental status, neurological deficits and laboratory findings improved or normalized. The association between TTP and solid tumor is well known.1 The diagnosis of TTP is challenging, because it is a rare disease with a variable presentation; early detection of this life-threatening condition and its correct treatment can save the life of the patient.

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A 49 year old woman was admitted to our Department with a twomonth history of progressive weight loss, fatigue and non-productive cough. On examination, the patient appeared to be fatigued, the blood pressure was 140/80 mmHg, the pulse 100 beats per minute, the respiration rate was 20 breaths per minute, the temperature was 37C and the oxygen saturation was 96% on room air. Moderate exophthalmia and mild bilateral expiratory wheezes were present. Abdominal examination revealed slpenomegaly. The remainder of the physical examination, including neurologic and skin examination, was normal. Laboratory tests showed findings compatible with her known microcythaemia (hemoglobin 9.2 g/dl, RBC 5.020.000, MCV 61 fl). Thyroid hormones (TSH 0.01uUI/ml,, FT3 4.6,pg/ml, FT4 1.93,mg/dl, anti TPO 398 UI/ml,, anti TSH-R 5.04 U/l) and pseudonodular areas on thyroid ultrasound were consistent with Graves’ Disease. Blood gas analysis revealed pO2 75 mmHg, ph 7.40, pCO2 43 mmHg, HCO3 26.6 mEq/l, sO2 96%, fiO2 21%. Pulmonary function testing was normal except for a mild diffusion impairment: FVC 2.87 L (110%), FEV1 2.37 L (107%), FEV1/FVC 0.82, DLCO 78%. During hospitalization, a chest radiograph was performed that showed diffuse pulmonary parenchymal infiltrates. The finding of constitutional symptoms, weight loss, and fever with this radiological pattern prompts a broad differential diagnosis that includes autoimmune disease, sarcoidosis, metastatic lung cancer and TB infection. Therefore, a total body CT scan was performed which revealed the presence of multiple areas of parenchymal consolidation with air bronchogram most prominent at the apical segment of the left upper lobe. The tuberculin skin test and autoimmune pattern were negative. The serum angiotensin-converting enzyme level was below normal limits (20 UI/L, range X-21 UI/L). A CT scan-guided needle biopsy specimen was then performed demonstrating evidence of non-caseating granuloma; stains for mycobacteria and fungal pathogens were negative and there was no evidence of cancer. These results were consistent with the diagnosis of pulmonary sarcoidosis. The patient was therefore treated with prednisone 30 mg per day and a reassessment was planned at one month to determine the possibility of tapering the dose. Sarcoidosis is a systemic granulomatous disease of unknown etiology characterized by thoracic involvement in up to 90% of patients regardless of the organ affected. The diagnosis is supported by the presence of compatible clinical radiologic findings, a tissue biopsy specimen that reveals non-caseating epithelioid granulomas and the absence of a granulomagenic agent1. The association of sarcoidosis and thyroid autoimmunity has been reported by different studies, but for Graves’ Disease only anecdoctal reports are present in the literature. For pulmonary sarcoidosis, there is no general consensus regarding which group of patients require treatment, the type of medication or the duration of therapy. Remission of sarcoidosis occurs for more than half of patients within 3 years of diagnosis and within a decade for two-thirds with few or no consequences so that many individuals require no treatment. Unfortunately, up to one-third of patients develop progressive and disabling organ impairment, such as respiratory failure due to pulmonary fibrosis. Therapy is often

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 started for patients who experience disabling symptoms, such as intractable cough or dyspnea on exertion or for pulmonary function deterioration. Therapy is aimed at reducing granulomatous inflammation and delaying the development of irreversible organ damage, such as honeycomb and fibrotic lung disease. Corticosteroids are the most effective treatment of sarcoidosis, but long-term treatment may result in disabling side effects. An alternative therapy with immunosuppressive drugs may be indicated for patients who cannot tolerate the adverse effects of glucocorticoids, whose disease cannot be controlled with a dose of 10-15 mg prednisone or less, or who have evidence of disease progression despite a moderate dose of corticosteroids. A variety of immunosuppressive agents have been used to treat refractory pulmonary sarcoidosis. The agents that appear to have the greatest likelihood of benefit with an acceptable side effect profile are methotrexate, azathioprina and antimalarial agents2. Tumor necrosis factor inhibitors, such as infliximab, recently have been used in refractory sarcoidosis because of the known role of TNF in the pathogenetic basis of the disease. Some benefits have been shown from TNF, but randomized clinical trials do not support their routine use. References 1. Newman LS, Rose CS, Maier LAN. Sarcoidosis. N Engl J Med. 1997;336(17):1224-34 2. Morgenthau AS, Iannuzzi MC. Recent advances in sarcoidosis. Chest. 2011;139(1):174-82

Hypomagnesemia and joint pain I. Giarretta, R. Pola, R. Manna, R. Landolfi Dipartimento di Medicina Interna e Scienze Mediche Specialistiche, Universita` Cattolica del Sacro Cuore, Roma, Italy A 56-year-old Caucasian woman, with a history of hypertension, dyslipidemia, and peripheral artery occlusive disease, presented to our Division of Internal Medicine with cramps, muscle weakness, aches of muscles and joints, and fatigue. These symptoms had started a few years earlier, but no clinical explanation had ever been found. The patient had also a history of recurrent joint effusions and pains affecting knees, shoulders, hips, and wrists. Two years before, the pain and effusion at the level of the right shoulder and left knee had become so severe that a surgical biopsy of the joint of the knee was performed and the histological examination demonstrated chronic inflammation of the synovial membrane with lymphocytes infiltration. Finally, the patient referred that, in the last 3 years, her blood tests had repeatedly shown low levels of magnesium (as low as 0.7 mg/dl, with normal range of 1.8-2.4) and, occasionally, low levels of potassium. During the hospitalization, the patient presented pain and swelling of the right knee. Low blood levels of magnesium were confirmed by our laboratory tests (0.8 mg/dl). Our initial hypotheses included gouty arthritis, an autoimmune disease with musculo-skeletal manifestations, psoriatic arthritis (the patient’s daughter was affected by psoriasis), and chondrocalcinosis. Uric acid serum level was normal. All the immunological tests that we carried out were negative. No evidence of psoriasis was found. We performed X-rays and/or ultrasonography of the knees, the wrists, the hips and the ankles, but no signs of enthesitis, dactylitis, or spondylitis were detected. Instead, there was ultrasonographic evidence of small calcifications of the triangular fibrocartilage of the wrist, as observed in the setting of chondrocalcinosis, We decided to perform an arthrocentesis of the right knee, which was, as mentioned above, painful and swollen during the hospitalization, and found calcium pyrophosphate dihydrate crystal deposition, consistent with a diagnosis of chondrocalcinosis. Chondrocalcinosis may be associated with hyperparathyroidism and hemochromatosis. However,

S217 the serum levels of parathormone, vitamin D, calcium, iron, and ferritin were normal. Chondrocalcinosis may be also associated with hypomagnesemia, as it was in the case of our patient. Therefore, it became mandatory to determine the cause of low blood magnesium levels in our patient. We considered inadequate magnesium intake, increased gastrointestinal or renal losses, or redistribution from extracellular to intracellular space. To investigate these hypotheses, we measured fractional excretion of magnesium and urinary calciumcreatinine ratio. These tests showed renal magnesium wasting and hypocalciuria with fasting urine calcium/creatinine ratio of 0.12 (normal [ 0.20). Based on the available data, we proposed a diagnosis of Gitelman’s syndrome, an autosomal recessive renal disorder characterized by hypomagnesemia, hypocalciuria, hypokalemia, and metabolic alkalosis. Indeed, in our patient, also mild hypokalemia and metabolic alkalosis were present. Subjects affected by Gitelman’s syndrome are usually diagnosed in adulthood during routine investigation and mainly present mild weakness, cramps, fatigue, and joint pain and effusions. We are currently in the process of confirming the diagnosis by the analysis of the SLC12A3 gene, which encodes the distal convoluted tubule Na–Cl cotransporter (NCC) and presents a homozygous loss of function mutation in subjects with Gitelman’s syndrome. However, it should be noted that more than 140 different NCC mutations have been identified in individuals with Gitelman’s syndrome and that the genetic tests currently available explore only a limited number of them. Therefore, the diagnosis of Gitelman’s syndrome may be formulated even in the absence of a positive genetic test, if the clinical and laboratory features of the disease are clearly evident, such as in our case. The patient is currently being treated with oral magnesium and potassium supplementation. She is also receiving treatment with valsartan, to help maintaining normal blood levels of potassium. For the treatment of chondrocalcinosis, she is receiving colchicine 1 mg daily and naproxen 500 mg daily, with weekly reduction.

Subacute abdominal pain caused by small bowel volvulus: a diagnostic challenge G. Grossi, A. Oldani, P. Sainaghi, G. La Terra, M. Pirisi Internal Medicine, Universita` del Piemonte Orientale ‘‘A. Avogadro’’, Novara, Italy Case report: An 80 years old male patient affected by alcoholic liver cirrhosis was referred to our Institution for abdominal pain, worsening stypsis and unintentional weight loss (25 kg during the last year). Clinical examination showed bad general conditions, BP 120/75 mmHg, diffuse abdominal pain particularly in umbilical area and weak peristalsis. Clinical history of the patient revealed a heavy alcohol consumption with proved liver damage, aorto – iliac substitution for common left iliac artery and internal right iliac artery aneurisms, and a previous episode of ileus that did not require any surgical procedure. To rule out cancer, chronic malabsorption, chronic infection, or worsening of chronic liver disease, the patient underwent to upper and lower intestinal tract endoscopy with mucosal biopsies, total body CT – scan, complete laboratory examination including AFP, PSA, anti – gastric mucosa antibodies, quantiferon, HIV tests; all these tests did not show pathological findings; an intestinal ultrasonography showed an evident thickening of some tracts of small bowel; fecal culture revealed Blastocistis hominis infestation, and a therapy with co-trimoxazole was started. Because of worsening of the abdominal symptoms with abdominal obstruction, the patient underwent to surgical evaluation and explorative laparotomy; unexpectedly an ileal volvulus was found and

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S218 distal ileum resected; postoperative stay was uneventful, with discharge in 10th day p.o. Histological examination revealed intestinal wall and mucosal atrophy, as for subacute ischemic condition. Discussion: Small bowel volvulus is a common cause of acute abdominal pain, that usually requires an immediate surgical approach, in order to avoid intestinal necrosis due to acute ischemia [1]. Causes of ileal volvulus are malrotation or congenital internal hernias (particularly in infants and young adults) and postoperative peritoneal adhesions (most common in elderly patients) [2,3]. In very rare cases, clinical presentation of volvulus causes subacute or chronic abdominal pain, associated to weight loss, stypsis or partial ileus, and worsening of general conditions; only few cases have been described in Literature [4]. Our experience showed a case of unexplainable subacute abdominal pain with no other recognizable pathological conditions except a probably intermittent ileal volvulus, causing partial ileus and chronic intestinal ischemia. References 1. Snyder JA, Lum C, Davidson MD. Elderly patient with small bowel volvulus. J Am Osteopath Assoc. 2010;110(11):678-9 2. Hanna T, Akoh JA. Acute presentation of intestinal malrotation in adults: a report of two cases. Ann R Coll Surg Engl. 2010;92(7): W15-W18 3. von Flue M, Herzog U, Ackermann C, Tondelli P, Harder F. Acute and chronic presentation of intestinal nonrotation in adults. Dis Colon Rectum. 1994;37(2): 192-8 4. Woon CY, Chung AY, Low AS, Wong WK. Delayed diagnosis of intermittent mesenteroaxial volvulus of the stomach by computed tomography: a case report. J Med Case Reports. 2008;2:343

Perirenal fluid collection: a possible cause of septic shock B. Lorenzati, F. Panero, M. Perotto Medicina Generale III, Dipartimento di Medicina Interna Ospedale Molinette, Torino, Italy A 83-year-old woman presented to the Emergency Department (ED) with worsening dyspnea, hypotension and fever (max 39C) since 2-3 days. She has also diffuse frank abdominal pain and a vascular dementia; as regard medical history she was a guest in a health care structure and there was no other significant things. Her pharmacology history was negative. On arrival in the ED she was hemodynamically unstable, unresponsive, with a pulse rate of 130 beats/min, right arm blood pressure of 80/55 mmHg, 39C of temperature and a respiratory rate of 30 breaths/min. Her physical examination revealed a tender right abdomen side with regarding and no other clinical findings. The abdomen was otherwise soft with no palpable masses, no renal bruits, and normal bowel sounds. Femoral pulses were present bilaterally and of equal character. She had wet, cold extremities with evidence of hypoperfusion. Chest radiographic were obtained and did not reveal any abnormal findings. The patient’s laboratory studies reveal increased white blood cell (WBC) 36500, chemistry panel remarkable for blood creatinine level of 3,98, PCR was 48 and some protein at the urine exam. According to her clinical features and laboratory studies we have assumed a septic shock of unknown origin. Thus we have performed an abdomen ultrasound in the ED to evaluate the inferior vena cava (IVC) excursion and to find a possible cause of the septic shock. We have found a complete collapse of IVC, no signs of colecistitis or of hydronephrosis; but we have found a perirenal fluid collection with a diameter of 14 cm (Fig 1) compressing the right kidney. According to the emergency ultrasound perform by the resident we have done an

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 abdominal computer tomography (CT) without contrast because of her renal failure. The CT has revealed a 11 9 12 cm mass, like fluid, compressing the right kidney and extending to the surroundings muscles planes (Fig 2). According to the principles in the management of septic shock, based on current literature, we have decided to treat both the septic shock and the cause of the shock. In the treatment of septic shock in crucial the early recognition, the early and adequate antibiotic therapy, the early hemodynamic resuscitation and the source control. A fluid challenge with 2000 cc of saline solution in bolus and antibiotic therapy were started according to the early goal directed therapy. In an attempt to remove the cause of the shock we have performed a drainage under ultrasound guide removing 450 cc of purulent-ematic fluid (Fig 3). One hour later the patient was hemodynamically stable, afebrile she has recovered her normal performance status and was ready to be admitted. This is a clear example of the utility of the bedside ultrasound, performed by emergency physicians/resident, during the evaluation of a critical ill patient. Although chest radiography and urine exam are the main two common exams to find a possible cause of the septic shock, we show that emergency ultrasound could be useful in this situation.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 References 1. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock. Crit Care Med. 2008;36(1):296-327 2. Nagdev AD, Merchant RC, Tirado-Gonzalez A, Sisson CA, Murphy MC. Emergency department bedside ultrasonographic measurement of the caval index for noninvasive determination of low central venous pressure. Ann Emerg Med. 2010;55(3):290-5 3. Rivers E, Nguyen B, Havstad S. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368-77

Guillain–Barre Syndrome B. Lorenzati, M. Perotto, F. Panero Medicina Generale III, Dipartimento di Medicina Interna Ospedale Molinette, Torino, Italy A 70-year-old woman presented to the Emergency Department (ED) with mild diarrhoea, evening fever (max 38C) for 10-14 days with worsening weakness and asthenia started in the morning. She has recently had a tour in Middle-East country (Uzbekistan, Tagikistan etc.). There was no other significant medical history. Her pharmacology history was negative. On arrival in the ED the patient was weak and asthenic, with a pulse rate of 50 beats/min, right arm blood pressure of 120/85 mmHg, 37,5C of temperature and a respiratory rate of 16 breaths/min. Her physical examination revealed a normal abdomen and chest. The neurologic examination revealed weakness and tingling sensations in her legs and hands, unsteady walking and numbness in her extremities. We hypothesized a electrolyte imbalance due to the diarrheal or a disorder in which the body’s immune system attacks the nerves (ex Guillain–Barre). Chest radiographic were obtained and did not reveal any abnormal findings. The patient’s laboratory studies reveal normal white blood cell (WBC), haemoglobin (Hb) and chemistry panel, only the PCR was 4.8. According to her important clinical features with normal laboratory studies and the sudden worsening of the symptoms we admitted the patient to the Neurologic Unit to evaluate the second diagnostic hypothesis. During the hospitalization they perform a first lumbar puncture which was negative and nerve function test which confirmed the diagnosis of Guillain–Barre. The lumbar puncture involves withdrawing a small amount of fluid from spinal canal at lumbar level. This cerebrospinal fluid is then tested for a specific type of change (elevated or rising protein levels on serial lumbar punctures and 10 or fewer mononuclear cells/mm3 strongly support the diagnosis) that commonly occurs in people who have Guillain–Barre syndrome, while electromyography reads electrical activity in the muscle to determine if the weakness is caused by muscle damage or nerve damage and nerve conduction studies assess how the nerves and muscles respond to small electrical stimuli. We decided to treat the patient because of the worsening of symptoms although we know that there’s no cure for Guillain–Barre syndrome; but two are the types of treatments speed recovery and reduce the severity of Guillain–Barre syndrome: plasma exchange (PE) and intravenous immune serum globulin (IVIG).The first, also known as plasmapheresis, is a type of ‘‘blood cleansing’’ in which damaging antibodies are removed from the blood. Plasmapheresis consists of removing plasma and separating it from the actual blood cells. The blood cells are then put back into the body, which manufactures more plasma to make up for what was removed. It’s not clear why this treatment works, but scientists believe that plasmapheresis rids

S219 plasma of certain antibodies that contribute to the immune system attack on the peripheral nerves. The second, intravenous immune serum globulin, contains healthy antibodies from blood donors. High doses of immunoglobulin can block the damaging antibodies that may contribute to Guillain–Barre syndrome. Each of these treatments is equally effective, both have been shown to shorten recovery time by as much as 50%. Mixing the treatments or administering one after the other is no more effective than using either method alone. IVIG is easier to administer and has fewer complications than PE. The cost and efficacy of each are comparable. Randomized trials in severe disease show that IVIG started within 4 weeks from onset hastens recovery as much as plasma exchange. Combining PE and IVIG neither improved outcomes nor shortened illness duration. Additionally, IVIG is the preferential treatment in hemodynamically unstable patients and in those unable to ambulate independently. Corticosteroids are ineffective as monotherapy. According to moderate-quality evidence, corticosteroids given alone do not significantly hasten recovery from GBS or affect the long-term outcome. In combination with IVIG, IV methylprednisolone may hasten recovery but does not significantly affect long-term outcome. Immune adsorption is an alternative that is still in the early stages of investigation. A small prospective study reported no difference in outcome between patients treated with immunoadsorption and those treated with PE. Many patients improve in a period of several months, approximately 30% of adults and more children, has residual weakness after three years. The residual defects may require the application of braces or corrective surgery. About 10% of patients relapse after an initial improvement, thus meeting a chronic relapsing polyneuropathy. References 1. Fergusson D, Hutton B, Sharma M et al. Use of intravenous immunoglobulin for treatment of neurologic conditions: a systematic review. Transfusion. 2005;45(10):1640-57 2. Hughes RA, Swan AV, van Doorn PA. Corticosteroids for Guillain-Barre´ syndrome. Cochrane Database Syst Rev. 2010;2: CD001446

Early systemic sclerosis, fever, pleural effusion and neutrophilic leukocitosis A. Marcoccia1, V. Antonini1, A. Ciani2, R. Vigliarolo2, T. Trequattrini2, S. Ramponi3, E. Cammilluzzi3, M.C. Zappa2 UOSD Angiologia; 2UOC Pneumologia; 3UOC Oncologia, Ospedale Sandro Pertini, Roma, Italy 1

On May a 46 year –old woman, presenting severe Raynaud’s phenomenon (RP) at the hands of recent onset, is ammitting to our angiology ambulatory. No personal history for significant diseases. Father died for lung cancer. She doesn’t take therapy except estrogenprogestin oral contraceptive. The patients suffers dryness and itching of the hands’skin during the night. The color Doppler performed upper limbs is negative for arterial or venous diseases. The videocapillaroscopy of nail fold highlights a ‘‘scleroderma pattern active’’. In the diagnostic suspicion of early systemic sclerosis she underdoes to many tests. Anti-nuclear antibodies(ANA) are positive with nucleolar pattern. ENA are negative. The Raynaud Condition Score (0-10) is 7. Respiratory function tests evidences slight reduction of diffusing capacity of the lungs for carbon monoxide (DLCO) as 75%. Echocardiography and the high-resolution computed tomography of the chest are negative. She is treated with calcium antagonist, gastric antisecretory, antiplatelet aggregation, antihistamines, low

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S220 dose steroid and is encourages to stop ongoing estrogen –progestin oral contraceptive therapy using alternative methods. The patient reports clinical improvement and reduction hands’ itching. In August the patient arrives at our observation for the appearance of pain and digital ulcer of distal phalanx first finger right hand. Iloprost ciclic therapy starts five days monthly with a resolution of the digital ulcer and lesion and disappearance of pain over the first month. Before starting third cycle of iloprost therapy the patient comes to observation reporting the onset of abdominal pain, constipation and bloating. Performing abdominal ultrasound, blood tests and faecal occult blood research which are all negative. A colonoscopy is scheduled, lactulose and probiotics are prescribed. After a week the patient presents fever onset (38.5 Celsius degree) not associated with other symptoms treated with acetaminophen. After three days for the clinical worsening conditions and the onset of cough and dyspnea goes to Emergency Department where chest x-ray shows pleural effusion associated neutrophilic leukocytosis (18,900 leukocytes with 80% neutrophils). She starts antibiotic therapy with cephalosporin II generation, quinolone antibiotic, macrolide and metilprednisolon (Urbason 20 mg every 12 h). The clinical and radiological course worsens. The patient is therefore subjected to a diagnostic thoracentesis and emptying. Culture and cytological exams of the same are both negative. After thoracentesis TC Chest highlights nodular parailar left lung training about 3 cm in diameter, with irregular margins. The patient’s clinical conditions worsening progressively: persistence of fever, dyspnea. The RX chest repeated at a distance of approximately 24 h after thoracentesis, shows the quickly recurrence of pleural effusion. The Thoracentesis repeated at a distance of about 48 h from the previous, taking approximately 1,200 cc of pleural fluid serous-blood. The cytological examination of centrifuged sediment highlights atypical cells whose morphology lays for undifferentiated type non small cell lung cancer (NSCLC). Leukocytes, monitored on a daily basis have a rapid ascent, reaching Leukemic-like values with peaks of around 73 9 103. The peripheral blood smear shows no such blastic elements. Bone marrow biopsy confirms increase of cells, with significant expansion of neutrophils line. The leukocytosis manifested in this patients, as confirmed by the data in the literature, is a consequence of increased production of Granulocyte Colony Stimulating Factor (G-CSF) by lung cancer, as a paraneoplastic form. In this case it is possible to use the White blood count (WBC) and the serum G-CSF levels as an additional tumor markers. To assess the sensitivity of cancer response to anti Epidermal Growth Factor Receptor (EGFR) monoclonal antibody therapy used alone in this pathology are investigated the activating mutations in Exon 19 and 21 of EGFR with techniques of molecular biology. These activating mutations results absent. Surgical therapy is excluded because it is not possible the radical surgery and a long convalescence of palliative surgery after intervening is not compatible with the rapid evolution of advanced neoplastic diseases. She’s been subjected to termoablazione of pulmonary parenchymal subperiosteal with reduction of quantity of cells secreting G-CSF. It’s been subjected to cytotoxic chemotherapy. The patient has been symptom free for three months. Raynaud phenomenon disappeared quickly during antineoplastic treatment and digital lesions doesn’t recurrent. Subsequently rapid recovery of neoplastic disease led the patient to death. A link between Systemic Sclerosis and malignancy is suggested by epidemiological evidence but the underlying mechanism connecting both diseases has been a source of ongoing controversy. In this case report, Early Systemic Sclerosis and NSCLC, occur within distance of time that early systemic sclerosis may be considered a paraneoplastic syndrome. This case concurrent to suggest that besides other possible mechanism, paraneoplastic etiology can be responsible for the association between SSc and cancer. That is to say we must pay attention to the sclerodermiform syndrome of recent onset because it may suggests the existence of an underlying neoplasm.

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 A case of invasive pulmonary aspergillosis P. Marinelli, M. Internullo, A. Russo, V. Fontana, L. Borgognoni, M. Villiva`, P. Baiocchi, E. Angelici, P. Palange Sapienza Universita` di Roma, Policlinico Umberto I, Dipartimento di Sanita` Pubblica e Malattie Infettive, UOC Medicina Interna I, Roma, Italy Case presentation: A 77 years old woman was admitted to the our department presenting with fever over 39C, productive cough and dyspnea. Patient’s medical history included chronic lymphocytic leukemia, complicated by neutropenia and hypogammaglobulinemia, diagnosed 17 years earlier and treated with cortisonic therapy. She also had a squamous cell carcinoma diagnosed two years earlier treated by local excisions. On admission laboratory findings revealed a lymphocytic leukocytosis with neutropenic state with 43.790 WBC (neutrophil count 740/mm3 and lymphocytes count 41.030/mm3), a moderate anemia with Hb 10.8 g/dl and a thrombocytopenia (platelet count 172.000/ mm3).The chest examination showed bilateral crackles. A chest X-ray showed ‘‘No parenchymal alterations’’. Arterial blood gas analysis showed a severe hypoxemia (PO2 62 mmHg, pC02 32 mmHg, PH 7.48). The differential diagnosis of a neoplastic and neutropenic patient presenting with fever and dyspnea is very broad. In these subjects is caused more frequently by lung infectious disease (fungi, virus, mycobacterium), pulmonary embolism and less frequently by paraneoplastic and autoimmune disease. A chest computed tomography was performed and showed ‘‘Ground-glass opacities mainly in the left lower lobe and lateral basal segment of the left lung’’. A sputum culture was made to identify bacteria and fungi proved positive for Aspergillus fumigates. On the same biological sample was made the detection of galattomannan that was positive with a cut-off more than 1. The detection of galactomannan (GM) is a new valuable test for diagnosing IPA. GM is a polysaccharide fungal cell wall component that is released during tissue invasion by Aspergillus hyphae and that can be detected in body fluids. If the performance of a bronchoscopy is considered to be contraindicated, microbiological examination of sputum can be useful. A recent study showed the sputum to be equivalent to BAL fluid for GM detection (1), at least in patients with hematologic malignancies (sensitivity and specificity of sputum and BAL were 100 and 62.2% 100%, and 83.3, respectively). Treatment of Invasive pulmonary Aspergillosis is challenging in this type of patients: the drug of choice is voriconazole (2). Antibiotic treatment with voriconazolo was started following an improvement in respiratory symptoms, chest examination and arterial blood gas analysis. References 1. Kimura SI, Odawara J, Aoki T et al. Detection of sputum Aspergillus galactomannan for diagnosis of invasive pulmonary aspergillosis in haematological patients. Int J Hematol. 2009;90: 463-70 2. Walsh TJ, Anaissie EJ, Denning DW et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:327-60

Skin lesions that ‘‘Still’’ last M.S. Masala, P. Meloni, A. Monni, V. Pretti, R. Ledda, F. Filigheddu, L. Cuccuru, G. Delitala Istituto di Clinica e Terapia Medica, Universita` di Sassari, Sassari, Italy

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 We describe the case of a 34 years old woman that came to our attention for an extensive eritemato-maculous and very pruriginous rash, tending to the confluence and extending to face, scalp, trunk, limb roots and extremities, that started two days before. Some months before the patient was diagnosed with Adult Still Disease, treated with top-down corticosteroid, with good results. After the withdrawal of therapy, the patient was in good condition and asymptomatic but one month later she started to have a continous fever with eveningspikes at 38-39C, arthromyalgias, sore throat and cutaneous rash characterized by esanthema limited to arms and feet. In the suspicion of flaring-up of Adult Still Disease, the patient was treated with oral prednisone (50 mg\daily) and hydrossichloroquine (200 mg\daily) without improvement. Because of the persistence of fever and sore throat, she assumed amoxicilline and clavulanic acid 2 g\daily for 3 days. On the third day, the fever and the sore throat disappeared but the coutaneous rash became makulo-papulous and extended to face, scalp, trunk, limb roots and extremities, with progressive centrifugal development associated with incoercible pruritus. The patient was then admitted to our ward. The physical examination, with the exception of the skin involvement was irrelevant. Blood tests were normal with the exception of increase in VES (78 mm/h), PCR (4.8 mg/dl), ferritina (5707 ng\ml), LDH (389 U\l), neutrophylia (28.47 9 103\mm3), thrombocytosis (501 9 103\mm3). We decided to stop the antibiotic therapy and the hydrossichloroquine and to administer methotrexate (10 mg weekly), oral prednisone (50 mg\daily), antihistamine and i.v. hydration. During the first days of hospitalization, although the skin lesions improved with a desquamative evolution, the pruritous became disabling and unresponsive to any antihistamine drugs but only partially to hydration. We excluded CMV and EBV infection and other infective conditions and we performed a cutaneous biopsy that showed a histological picture compatible with Still disease (infiltration of granulocytes and lymphocytes in perivascular part of the derma). The fourth day, the patient presented a new onset of the rash: the skin lesions extended to the whole body becoming rilevated, symmetric, polymorphic and extremely pruriginous and painful. Furthermore, an important eosinophilia appeared (3 9 103\dl) and lasted for some days. We excluded the main causes of eosinophilia and we decided to give i.v. Metilprednisolone (40 mg daily). Bandage with olive oil and vaseline produced a partial benefit on the symptomatology. A biopsy of a new skin lesion was repeated: it showed a condition of toxydermia and epidermolysis likely linked to a toxic drug reaction. The patient continued cortisonic, antihistaminic and hydrating therapy for 20 further days with slow normalization. Conclusion: This case is very interesting for two reasons: First, a toxydermic process developed on skin lesions already present, due to Still disease; the involvement was blunted probably by the ongoing cortisonic therapy and for this reason not exploded in a classic Stevens Johnson reaction. Second, the skin lesions had a new flaring, starting ten days after the withdrawal of the drug and under high dose cortisonic therapy. Probably the culprit drugs were amoxicilline, clavulanic acid or hydrossichloroquine.

S221 quadrant associated with weight loss of about 9 kg for about 8 months. Pain reported by the patient presents as a continuous gravatar pain, not associated with nausea and/or vomiting nor related to meals or bowel function. The patient appared in good general condition but had a distended abdomen, treatable, painful in the right and left iliac fossa and hypogastric with ascite. A palpable mass of hard consistency, adherent to the deep abdominal layers was identified. Vital signs were normal with exception of TA 37.8. Blood tests were normal with the exception of increase in VES(35 mm/h), PCR (3.7 mg/dl), alfa1(0.43 g\dl), alfa2(0.80 g\dl) and positivity of tumor markers (CYFRA 21.1 : 8.7 ng/ml e CA 125 : 235 U/ml). Abdominal ultrasound was performed showing the presence of ascites without other clear pathological findings. Ascitic fluid, removed by paracentesis and analyzed, shows abundant red blood cells and lymphocytes, few granulocytes, numerous and irregolar pleomorphic mesothelial cells, rare clusters of epithelial cells of possible ovarian or endometrial origin. A pelvic examination with transvaginal ultrasound showed a thickened endometrial; the biopsy was normal. At the abdominal CT with contrast the walls of ascending colon were thickened with stenosis of the lumen. Concomitant thickening of the mesentery and walls of some bowel loops as peritoneal dissemination was present. At the Colonscopy the proximal ascending colon and caecum were stenotic as possible extrinsic compression. To complete diagnosis work-up a bilateral breast ultrasound and mammography were performed. The results were negative. Therefore, the patient underwent a laparoscopic exploration that showed a diffuse peritoneal carcinomatosis, macroscopically compatible with colonic origin and with positive biopsy for solid epithelial malignancy. Immunohistochemistry cells were positive for CK 7, E cadherin, estrogen and progestin receptors, Mib 1 35%. The immunophenotypic profile and the patient’s medical history standed for localization of breast ductal carcinoma. The review of slides of peritoneal biopsy performed in a center different from ours confirmed the hypothesis of metastatic breast cancer. The review of the old breast slides confirmed the previous diagnosis of DCIS. The patient began chemotherapy for metastatic breast cancer according to weekly scheme paclitaxel 80 mg/mq. Conclusions: the peculiarity of this case resides in: 1- the fact that a distant breast cancer metastases after a diagnosis of pure ductal carcinoma in situ is rare, in fact in DCIS confinement of tumor cells by an intact basement membrane theoretically precludes the possibility of metastases. 2- that most patients who develop distant breast cancer metastases after a diagnosis of pure DCIS have an intervening invasive locoregional recurrence located at ipsilateral breast, axillary lymph nodes, chest wall, supraclavicular lymph nodes, while sites of distant metastases usually included bone, lung, remote lymph nodes and skin. Nonetheless these rare events highlight the heterogeneous behaviour of DCIS lesions and its potential risk of recurrences.

Psoriasic arthritis enthesitic outset: description of a clinical case A. Matarangolo, V.C. Rollo, I. Pappalardo, G. D’Alessandro

An apparent resolved issue M.S. Masala, P. Meloni, M. Carbini, A. Lai, V. Di Cesare, P. Salaris, R. Ledda, F. Filigheddu, L. Cuccuru Istituto di Clinica e Terapia Medica, Universita` di Sassari, Sassari, Italy We describe the case of a 63 year old woman with history of bilateral chronic glaucoma treated with timolol and previous DCIS(Ductal Carcinoma In Situ)in 2005 with negative follow up, who came to our observation for the onset of abdomnal pain localized to the lower

Clinica Medica Azienda Ospedaliera Universitaria, Ospedali Riuniti di Foggia, Centro studio malattie apparato osteoarticolare ed immunoproliferative, Foggia, Italy Objective: Psoriasis is a multifactorial disease sustained by chronic inflammation and immunological abnormalities, with skin and systemic manifestations, that leads to a wide spectrum of comorbidities. It’s often associated with anxiety disorders, depression, metabolic disorders and, above all, Psoriatic Arthritis (APs). It affects 2-3% of the general population without preference of sex; in this rate of patients, APs incidence is about 5-42%.

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S222 Although it’s intended less aggressive than Rheumatoid Arthritis (RA), the APs must be considered an erosive disease and thus disabling, especially for those young patients suffering from the polyarticular form. Small joints of the hands and feet and large joints are generally affected asymmetrically, rarely the beginning of arthritis may be symmetric. The inflammation of serous bags (bursitis), tendons (tendinitis) and history of Achilles tendonitis and talalgias (a kind of enthesitis, inflammation of the bony tendons) are also very frequent. Methods: We describe the clinical case of a young woman: she suffered from pain and swelling of the heels persistently for about 2 years. She also complained difficult walking, knee pain, arthralgia of the wrists and hands, but she presented only one episode of acute arthritis. Result: The patient was subject to laboratory and instrumental tests, which results oriented us to the diagnosis of Psoriatic Enthesitis. Hence we started the anti-inflammatory therapy with an anti-COX-2 (Celecoxib), obtaining the improvement of the symptoms. After few months, the patient turn back to our clinic observation because of an acute exacerbation of the symptoms: then we chose to add an inhibitor of Tumor Necrosis Factos- a (TNF-a) (Etanercept) to her therapy. After a new clinical evaluation at 4 months, her health conditions were really satisfying with complete remission of the disease and discontinuation of therapy. Conclusion: We’ve often experienced an incomplete control of local pain and an unsatisfactory effect of anti-COX2 in arresting the inflammatory process in patient with APs complicated by enthesitis. Therefore in the absence of literature evidences about the effectiveness of DMARDs in stopping the progression of joint enthesitic damage, we suggest two possible treatment options: the infiltration with corticosteroids or therapy with anti-TNF-a. Our choice fell on the use of an anti-TNF-a (Etanercept), which obtained complete control of the symptoms with a significant improvement in quality of life. It will be interesting to observe the persistence of the benefits resulting from the use of anti-TNF-a by ultrasound and radiological controls. References: 1. Ball J. Enthesopathy of rheumatoid arthritis and ankylosing spondylitis. Ann Rheum Dis. 1971;30:213-23 2. Ritchlin C. Psoriatic disease–from skin to bone. Nat Clin Pract Rheumatol. 2007;3(12):698-706 3. Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H; CASPAR Study Group 4. D’Agostino MA, Olivieri I. Enthesitis Best Pract Res Clin Rheumatol 2006;20:473-86 5. Benjamin M, McGonagle D. The anatomical basis for disease localization in seronegative spondyloarthropaty at enthesises and related sites. J Anat 2001;199:503-26 6. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum. 2006;54(8):2665-73 7. McGonagle D. Diagnosis and treatment of enthesitis. Rheum Dis Clin N Am. 2003;29:549-60

A fever doesn’t speak early A. Monni, D. Concu, D. Riccio, V. Pretti, M. Masala, R. Ledda, F. Filigheddu, L. Cuccuru, R. Tedde, G. Delitala Istituto di Clinica e Terapia Medica, Universita` di Sassari, Sassari, Italy A 72 years old woman was admitted to our Clinic due to fever of unknown origin which had started one month before. The patient medical history started 3 months before when dental abscess appeared. The dentist drained it and prescribed an antibiotic treatment with remission. One month after painful white lesions appeared under the tongue. No other symptoms or signs were reported. In the suspicion of candidosis

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 the patient was treated with a topic antifungal without remission of the lesions. For this reason she was treated with systemic antifungal. Oral lesions disappeared but since than the patient had fever. It was intermittent in spite of thermic curve was distort by antipiretic and antibiotic drugs. For this reason she was admitted to an Internal Medicine ward where she performed blood analysis, cultural tests on blood, urine, feces, lung radiography, abdominal and cardiac ultrasounds, total body C. T. and bone marrow biopsy. All these examinations did not reveal any alteration except normochromic and normocytic anaemia (Hbg: 9,4 g/ dl) and an increase in PCR (6,6 mg/dl). Come to our attention the axillary temperature was 38,9C. The patient felt sick and others symptoms were non productive cough and temporary dyplopia. Acute neurological disorders were excluded. In the suspicion of infectious fever we repeated Quantiferon and cultural tests for B.K., abdominal and cardiac ultrasounds, WidalWright reaction, anti-EBV, anti-CMV and anti-HIV antibodies. Widal-Wright reaction was positive and we started antibiotic treatment with ciprofloxacin. Nevertheless the fever didn’t disappeare. In order to exclude an occult lymphoma or other neoplasias we performed PET scan that showed high metabolic activity injuries in the left occipital lobe. So we performed brain MRI that showed ischemic lesions in various stages of development and in various locations. Carotid ultrasounds was normal. Meanwhile a new symptom appeared: headache. Neurological evaluation revealed at this point a right homonymous lateral hemianopsia. In the suspicion of vasculitis a functional MRI was performed: recent and old cerebral lesions were confirmed. The patient was treated with top-down corticosteroid therapy. The fever disappeared but hemianopsia remained as a relics. A MRI repeated after two months showed a remission of the lesions. Conclusions: this case is interesting because the patient had a clinical presentation that required a very difficult differential diagnosis, because vasculitis with intracranial localization is an unusual cause of stroke and because we were doubtful till the end whether or not to treat the patient.

A strange case of thrombocytopenia C. Oneto, C. Passalia, P. Minetto, S. Karamichali, I. Ponassi, A. Bellodi, R. Ghio Clinica Medicina Interna Iii, Azienda Ospedaliera San Martino, Genova, Italy A 64 years old woman was visited in our Internal Medicine outpatient clinic because of persistent thrombocytopenia in absence of bleeding diathesis. The patient was asymptomatic. She denied bleeding events in her lifetime. On physical examination were notable breath sounds diminished with faint, high-pitched rhonchi toward the end of expiration; no peripheral edema in the legs; oxygen saturation was 93% while the patient was breathing ambient air; spleen was palpable during deep inspiration; no superficial lymphoadenopathy, petechial or purpuric lesions; no other significant findings Her blood count was the following: WBC: 3,900/mm3 (N 57.6%; L 32.7%; M 8.7%; E 0.7%; B 0.3%); Hb 13.6 g/dl; MCV 90; Plt 84,000/mm3. The patient was a no-smoker, no mention of alcohol abuse, no occupational risk; she had a long history of moderately severe chronic obstructive pulmonary disease (COPD); 6 years ago, right lower limb melanoma was treated with surgical excision; an adrenal left pheochromocytoma, discovered 3 years later under follow up for melanoma, was treated surgically; no abnormal bleeding were reported during dental extraction, childbirth and surgery. She had two sons in good health whereas a brother and a sister no

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 smoking, were suffering from COPD. Six months before, an digestive endoscopy revealed atrophic gastritis, no esophageal varices. Her medications were only bronchodilators and inhaled-corticosteroid medications. No chemo-radiotherapy was reported. A whole computed tomography scan recently carried out in oncology follow-up, revealed bubbles of emphysema, splenomegaly (15 cm) and slightly irregular liver margins, non-enlarged lymph nodes. At first evaluation, the patient history wasn’t suggestive of iatrogenic cause for the presented clinical feature. Further investigations ruled out infectious, autoimmune or hematologic aetiology of cytopenias and liver disease: no increase of inflammatory markers was observed, virological investigations were negative, a peripheral blood smear showed no morphologic abnormalities. The bone marrow examination excluded myelophthisis, myelodysplastic syndrome and myelofibrosis; furthermore there was no megakaryocytic increase, typical of idiopathic thrombocytopenic purpura. The vitamin B12 and folate, dosage lipid profile, thyrotropin, glycated hemoglobin were normal. Noteworthy biochemical examinations remarked minor, occasional increase of cholestasis and cytolisis hepatic (twice the standard), serum albumin and coagulation were normal, protein electrophoresis pointed reduction of alpha protein in absence of qualitative changes. A spirometry was also performed which evidenced severe obstruction and reduction of alveolar capillary diffusion of CO. An Doppler ultrasound showed fatty liver but no sign of portal hypertension (portal and splenic veins diameter normal, preserved and orthograde portal flow).The most likely cause remained therefore a thrombocytopenia due to splenomegaly secondary to liver disease. But what was the cause for the liver disease? Re-evaluating the patient family and personal history, the occurrence of COPD in absence of exposure to smoke or to occupational risk (both in herself and in her first-degree relatives) and liver disease with reduction of alpha proteins suggested us to search for the assay of alpha 1 antitrypsin (ATT) which resulted heavy deficient. The genetic analysis confirmed a hereditary deficiency of alpha 1 antitrypsin with homozygous ZZ protein phenotype, which well explains clinical feature. Liver biopsy was refused. The patient therefore started replacement therapy and we propose genetic analysis for family members. Thrombocytopenia alone in alpha 1 antitrypsin deficiency patient is not reported in literature, while respiratory involvement is often predominant feature. In our patient, the misunderstood disease had slow progression due to her healthy habits, nevertheless resulting in severe COPD and in liver disease with secondary thrombocytopenia. Treatment with bronchodilators and inhaled-corticosteroid medications, pulmonary rehabilitation and early antibiotic therapy of all exacerbation are recommended, as in cases of COPD unrelated to AAT deficiency, with increased intensity of therapy guided by disease severity (following Guidelines of AAT Deficiency Task Force). Specific therapy for AAT deficiency-related lung disease is available as intravenous augmentation therapy with partially purified plasma preparation highly enriched for AAT. Several observational studies have suggested that AAT augmentation therapy may slow the rate of decline in lung function in the subgroup of AAT-deficient patients with moderate-to-severe airflow obstruction (variably defined in different studies). On the contrary, specific therapy is not currently available for liver disease, because AAT augmentation therapy is not effective. Hepatitis A and B, pneumococcus and annual influenza vaccines are recommended for all AAT-deficient patients. There is no evidence to support the use of replacing therapy in AAT-deficient patients with normal lung-function tests.

The dark side of macrophages V. Pacetti, L. Caliari, F. Meda, C.F. Selmi, M. Podda IRCCS Istituto Clinico Humanitas Rozzano (MI), Italy

S223 A 50-year-old man was admitted to the emergency department (ED) of our Institute following the sudden appearance of thoracic pain, dyspnea, and fever (up to 37.5C) previously treated with levofloxacin. Blood tests at the ED demonstrated a normal white cell count, elevated C-reactive protein (48 mg/dl, nv \ 1) and D-dimer (5,000 ng/ml). A chest X-ray showed an inflammatory shadow in the lower right lobe of the lung with lymph node enlargement under the carena, confirmed by a chest CT scan. The scan also demonstrated the embolism of a branch of the left pulmonary artery and its segmentary ramifications that supply blood to the lower left lobe and in the pulmonary artery ramification supplying the lingula. In consideration of the lack of pneumonia resolution with first-line empirical treatment, the patient underwent to a fibrobronchoscopy with bronchoalveolar lavage (BAL) to investigate the etiological agent and to lymphocyte immunophenotyping, quantitative IgG determination, and HIV antibody test to rule out a cell-mediated and/ or humoral immune deficiency reporting only a BAL positivity for Klebsiella pneumoniae. The microorganism was sensitive to the ongoing second-line empirical iv treatment with piperacillin/tazobactam and amikacin. Because of the pulmonary embolism the anticoagulant treatment was started. Screening tests for tumor and thrombophylic status were performed and gave negative results. Progressive improvement of the respiratory distress, defervescence, and inflammatory markers normalization were observed. On the eighth day following admission, new episodes of fever (up to 38C) reappeared without other symptoms and were responsive to administration of oral and iv acetaminophen. Suspecting a Gram positive superinfection, teicoplanin was added, and over the following days the patient fever disappeared while additional blood cultures were negative. On the 13th day, fever (up to 39.5C) returned associated with shivering and partial response to acetaminophen. Initially, blood tests showed a stability of inflammatory markers with an increase of C-reactive protein (2 mg/dl) and of the white blood cell count (14,000 cells/mm3). Piperacillin/tazobactam and amikacin were withdrawn and a fibrobronchoscopy with BAL was repeated (resulting negative for pathogenic bacteria) followed by the empirical introduction of meropenem iv. In the third week following admission, leukopenia with absolute lymphopenia (as low as 200 lymphocytes/mm3) was observed in the absence of serum evidence of viral infection (negative CMV, EBV, Toxoplasma, HSV 1 and 2, adenovirus IgM) and a palpable purpura on the back and then on the superior and inferior limbs appeared along with thrombocytopenia (as low as 28,000 platelets/mm3) and anemia (Hb 7 g/dl). To clarify the hematologic and cutaneous scenario and suspecting immunomediated, parainfectious, or paraneoplastic vasculitis, autoimmune serum markers (ANA, ANCA, complement components C3 and C4) were tested and a thoraco-abdominal CT scan performed without significant findings. Kidney function tests remained normal, a peripheral blood smear showed no evidence of platelet clumps and schistocytes and a skin biopsy ruled out embolic features to ultimately exclude Moskowitz Syndrome. Suspecting a drug-related or a heparine-induced thrombocytopenia, antibiotic therapy with teicoplanin was withdrawn and nadroparin was replaced with fondaparinux. Taking notice of elevated ferritin (19,000 ng/ml), triglycerides (426 mg/ dl), fibrinogen (870 mg/dl) and reduced platelet count, associated with the fever, the diagnosis of infectious-related macrophage activation syndrome (MAS) was suspected. A cytologic bone marrow exam demonstrated erythropoiesis associated with hemophagocytosis and confirmed the diagnosis. iv therapy with desametason was then started with prompt defervescence and resolution of the skin lesions but no effect on the blood cell counts. Therapy with high dose iv immunoglobulins was hence started allowing a slow but continuous improvement of hematologic alterations until discharge after 30 days (Hb 7.6 g/dl, Ht 22.2%, MCV 93.6 fl, reticulocytes 0.7%, WBC 4,600/mm3, N 3,000/mm3, L 900/mm3, Plts 181,000/mm3, ferritin 2,149 ng/ml).

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Consideration on a case of chronic diarrhea illustrative of the internist approach P.P. Papappicco, G. Lorusso, S. Cicco, G. Greco, S. Antonaci, G. Giannelli Dipartimento di Clinica Medica, Immunologia e Malattie Infettive Policlinico di Bari, Bari, Italy We describe the case of a 74-year-old man who came to our observation for chronic diarrhea, non responsive to loperamide; he was confined to bed, underweight (BMI 17) and depressed. He had a history of arterial hypertension and a depression syndrome, in treatment with selective serotinin reuptake inhibitors (SSRI). The diarrhea had lasted about 1 year, accompanied by loss of appetite and weight loss; he had undergone gastroenterologic visits, gastroscopy and colonscopy, showing chronic H. pylori-correlated gastritis and colonic diverticulosis. H. pylori-eradicating therapy was started, as well as chronic treatment with proton pump inhibitors (PPI). Due to the persistence of the diarrhea, he was admitted to an Internal Medicine ward and then discharged with a diagnosis of colonic diverticulosis and a prescription for rifaximin and mesalazine therapy. Due to worsening of the diarrhea and further weight loss (10 kg in the last year), anorexia and worsening of the depression, the patient was then admitted to our Operative Unit. Laboratory tests showed a state of inflammation and malabsorption, excluded autoimmune disease (negative anti-transglutaminase antibodies, ANA, ANCA, ENA and ASCA), infectious disease (serodiagnosis of Widal-Wright syndrome, fecal culture and parasitology tests, negative fecal H. pylori antigen), endocrinologic disease (normal VIP, chromogranin, gastrin, 5HIAA and thyroid hormones) and neoplastic disease (negative neoplastic markers and SOF, a macroscopically normal colonoscopy and hence no biopsy advised by the endoscopist). The suspected diagnosis was ‘‘microscopic drug-induced colitis’’, an inflammatory disease of the colon characterized by a normal endoscopic appearance of the colon and a lymphocytic infiltrate of the bowel mucosa at microscopic examination. Therapy with lansoprazole was suspended, but no clinical benefit was observed, and a psychiatric consultation was performed. Due to persistence of the symptoms, paroxetin therapy was replaced by a tricyclic antidepressant drug, which induced a rapid improvement of the clinical and laboratory pictures. One month after discharge, the patient was symptom-free, referred a weight increase by about 5 kg and an improvement of his depression. Recent studies have reported an association between microscopic colitis and various drugs used very widely in internal medicine wards (NSAIDS, PPI, SSRI, b-blockers, statins, biphosphonates, ticlopidine). This case illustrates a typical example of the internist method, that takes into account all the diagnostic possibilities, and if necessary goes against the suggestions of other specialists involved in the case. It should be underlined that the final diagnosis was not the fruit of expensive, technologically advanced and invasive tests but of a meticulous clinico-methodological assessment.

Case report: L.A.M., an 84-year-old female. The patient was admitted to the Emergency Medicine ward for acute decompensated heart failure. The vital signs at presentation were the following: BP 130/70 mmHg, HR 98/bpm, SpO2 93%. Rest ECG showed non-specific changes of T waves. A chest US was performed; this examination showed a bilateral pleural effusion and a distension of inferior vena cava. Cardiac US showed an hypertrophy limited to the apex of the left ventricle, with relative sparing of basal segments (spade-like configuration). A diagnosis of apical hypertrophic cardiomyopathy was made. A therapy with ACE-inhibitors, beta-blockers and intravenous diuretics was started. The patient was discharged 4 days later. Six months later she complained of mild dyspnea on exertion (NYHA II). Conclusions: Apical hypertrophic cardiomyopathy is an uncommon cause of acute decompensated heart failure. Diagnosis is made with the transthoracic echocardiography. It’s important not to miss this diagnosis, because of the better prognosis in comparison to the more common forms of hypertrophic cardiomyopathy.

Next-door pulmonary embolism E. Pennacchio1, M. Martorano1, G. Viggiano1, M. Ricapito1, D. Maroscia2, M. Autilio1 Pronto Soccorso, Accettazione e Medicina d’Urgenza; 2Radiologia d’Urgenza, A.O.R. ‘‘San Carlo’’ Potenza, Italy

1

Introduction: One of the risk factors for pulmonary embolism (PE) is active malignancy. We report a case of PE in a patient with a unique kind of neoplastic lesion. Case report: P.G., male, 96-year-old. One year before the patient underwent resection of a malignant melanoma of the trunk. He reached the emergency department for dyspnea and syncope. At presentation, the vital signs were the following: BP 100/50 mmHg, HR 115/min, SpO2 88%; the patient was breathless, pale, cold-sweated. A CT scan of the thorax was performed, that showed thromboembolic disease of the main pulmonary vein branch and of the lobar branches on the right and of the lobar superior branch and of segmentary inferior branches on the left. The US compression of the veins of the arms and legs didn’t show pathological findings. The patient was admitted to the Emergency Medicine ward and treated with low molecular weight heparin. A bedside echocardiography performed the next day showed a mass in the right atrium through the tricuspid valve during each cardiac systole. This mass was suspected to be a metastasis of malignant melanoma. The patient died at home 3 months after being discharged; the autopsy wasn’t performed. Conclusions: Cardiac metastases are common in patients with metastatic cancer; missing the diagnosis of cardioembolic PE may lead to useless and potentially harmful therapy, such as the positioning of a caval filter (Borsaru, BJR 2007). Echocardiography is essential to suspect the diagnosis and plan the correct therapeutic strategy.

A case of heart failure due to an uncommon disease A common complication of an uncommon cause of ascites E. Pennacchio1, G. Gaudino1, G. Staffa1, S. Limauro1, M. Caiazza2, M. Autilio1 1

2

Pronto Soccorso, Accettazione e Medicina D’urgenza; Servizio di Cardiologia, A.O.R. ‘‘San Carlo’’ Potenza, Italy Introduction: We frequently manage, in the Emergency Medicine ward, patients with acute decompensated heart failure. We report a case of heart failure due to an uncommon form of heart disease.

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M. Perotto, F. Panero, E. Greco, P. Fornengo, P. Cavallo Perin, G. Bruno Universita` degli Studi di Torino, Dipartimento di Medicina Interna, Torino, Italy A 60-year old woman was referred by her general practitioner to our Hospital for asthenia and ascites. At first glance, she looked well,

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 vital parameter were normal; anamnesis was unremarkable except that for hypothyroidism and essential hypertension for which she had been treating with L-thyroxin and an ACE-inhibitor; she did not report loss of weight, nocturnal sweating, pruritus, abdominal or chest discomfort, any episode of jaundice, dyspnea or orthopnea, ankles swelling, abnormal rectal or vaginal bleeding (menopause had begun when 52 years old) or hot flushes, recent constipation or diarrhea or diuresis contraction. Thoracic and abdominal examinations were normal apart from a distended abdomen with a shifting dullness. All blood measurements as well as markers for B and C hepatitis, quantiferon test for tuberculosis, alfa-feto protein were unremarkable except that for mild Ca-125 rise and gamma-globulin decrease. A bed-performed echography confirmed the presence of abundant liquid among intestinal loops, discovered a narrow layer of bilateral pleuric fluid and a 3 9 3 cm hypoechogenic mass placed on the fundus of uterus; liver, spleen, pancreas and kidneys appeared normal, portal circulation was preserved. As little fluid was placed under the peritoneal sheet, we initially abstained from performing a diagnostic paracentesis. Our primary hypothesis was a gynecologic neoplasm despite only mildly elevated Ca-125 marker. Common causes of ascites should include those generating a transudate rather than an exudates: among the formers, most common are cirrhosis (viral, alcoholic, primitive or secondary biliary, etc), heart failure, nephrotic and uremic syndrome, hypothyroidism; among causes of exudative fluid ascites there are neoplasia, infections such as tuberculosis, perforation of an abdominal organ, autoimmune serositis such as those seen in lupus syndrome, actinic serositis. Morphologic typization of the mass might have done by CT of thorax and abdomen; finally, only cytological examination of the ascitic fluid or biopsy of that mass would have made a diagnosis. On day two, a CT of thorax and abdomen with contrast medium confirmed the presence of an adnexal mass engaging the left ovary, peritoneal carcinosis with ‘‘omental-cake’’ aspects, abundant ascites and a 1.5 cm bilateral pleural effusion. The next day, the trans-vaginal echography confirmed the presence of hypoechogenic mass of the ovary not suggestive for a cystic lesion. Gynecologic examination and mammography were unremarkable. Taking into account previous history and current presentation, we considered as likely diagnosis a gynecological cancer (adeno-carcinoma of the ovary—despite mild Ca125 elevation—leyomiosarcoma of the uterus), ax extrinsic cancer of the gut, a GIST, a sarcoma. In the next 2 days the patient became dyspnoic and showed an obliged left lateral decubitus where both bronchial blow and hypophonetic area were audible, her saturation was 94% and respiratory rate was 30/min. She had gained about 4 kg in 5 days and abdominal circumference had consistently increased. Thoracic echography demonstrated a conspicuous left pleural effusion: a therapeutic and diagnostic echo-assisted thoracentesis was done with removal of almost 1 l of clear yellowish fluid. An evacuative paracentesis was also performed: 4 l of fluid similar to the pleural effusion were drained and samples sent for analyses. The patient reported profound asthenia and looked very tired. On day five, biochemical analysis confirmed the exudative nature of both pleuritic and ascitic fluid; cytological examination did not find any abnormal epithelial cell suggestive for a carcinoma but the pathologist highlighted the massive presence of B-lymphocytes. By the day six, we progressively assisted to worsening of renal function: urine analyses revealed low-grade proteinuria and high concentrations of uric acid salts. Urgent dosages of electrolytes, LDH and serum uric acid confirmed the suspect of acute tumor lysis syndrome. Hydration with physiologic solution (3–4 l/day), rasburicase and following allopurinol administration, daily dosage of electrolytes, creatinine and serum uric acid and diuresis collection were begun. The occurrence of both tumor lysis syndrome and many B-lymphocytes on ascitic fluid supported the diagnosis of a B-cell lymphoma of the abdomen. A sample of ascitic fluid was sent for immune-histochemical examination which confirmed a high grade B-cell lymphoma compatible

S225 with a sporadic form of Burkitt lymphoma. Sporadic Burkitt lymphoma is an uncommon variant of the more known endemic form spreading in some areas of Africa and among immune-depressed individuals; its usual presentation is an abdominal emergency such as gut perforation, bleeding or occlusion; it’s less likely to begin as an abdominal mass with ascitic effusion. Early aggressive chemo-therapy is the treatment of choice as this kind of lymphoma has a very good prognosis among full respondents. The development of a tumor lysis syndrome should have promptly addressed us to an haematological neoplasia, but it is also not uncommon for germinal cancers (such as of ovaric origin) even when therapies have not still begun. Nevertheless, the rapid deterioration of this patient’s conditions and the absence of a severe elevation of Ca-125 were compatible with a high-grade lymphoma. The patient was then transferred to an oncologic clinic, were a central venous catheter was then placed, a second evacuative paracenthesis, three dialytic sessions for life-threatening hyperuricemia and hyperphosphatemia were done too; low dose chemotherapy with IV dexamethazone and vincristine were started too. FISH analysis and immuno-histochemical confirmed initial suspect of sporadic Burkitt lymphoma. Serologic tests for HIV and cytomegalovirus were negative. The patient entered a standard protocol for high grade B-cell lymphoma. Three months after diagnosis she is still alive: she in post-chemotherapy bone marrow aplasia and no opportunistic infections have intervened. She autonomously walks and attends her daily home activities.

An uncommon cause of neck swelling M. Perotto, F. Panero, B. Lorenzati, G. Sgro`, P. Cavallo Perin, G. Bruno Universita` Degli Studi di Torino, Dipartimento di Medicina Interna, Torino, Italy A 69-year-old woman was conducted to the Emergency Department for progressive dyspnea, cough with yellowish sputum, haemoptysis and fever in the last 3 days. At admittance, the patient was awake and reported mild dyspnea with no other symptoms. The vital parameters were: blood pressure 180/95 mmHg, heart rate 76 bpm, respiratory rate 20 breaths/min, peripheral arterial oxygen saturation 91%, temperature 38.5C. Physical examination was unremarkable except for a reduced vesicular murmur bilaterally and a 2 cm 9 2 cm mass in the upper third of the left sternocleidomastoid muscle edge, which was mobile laterally but not vertically; no tenderness or any signs of local inflammation were evident. No signs of heart failure were present. She reported a left hip prosthesis intervention, breast cancer excision (with negative follow-up) and left fibrothorax diagnosed in 2008. The patient had undergone a dental procedure a month before hospital admission; then she had noticed a swelling area beside the left jaw angle, which had been progressively increasing in the last 10–15 days. In preceding weeks, the patient noticed a sharp increase in her blood pressure (max 200/100) concomitantly with several episodes of headache. She also reported fatigue and night sweats since about 2 months. ECG showed sinus rhythm; hemogasanalysis on room air showed a mild respiratory failure with uncompensated respiratory alkalosis. She was placed on oxygen supplementation with Ventimask 31%; chest X-ray study highlighted a left fibrothorax without either pulmonary or pleural lesions. The patient was initially isolated till the analysis for Koch bacillus on sputum and quantiferon test were negatives as well as hemocultures, sputum cultures and urinary antigens for Legionella and Pneumococcus. Laboratory blood examinations showed an increased PCR with neutrophil leucocytosis. A chest CT scan was unchanged with respect to 2008 except that for a postero-basal condensation suggestive for a pneumonia. The patient was successfully treated with empirical antibiotic therapy and a diagnosis of community acquired pneumonia was drawn. The undefined mass on the neck was then examined.

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S226 Anterior triangle masses pose an important dilemma: most common neck masses are lymphoadenopathies secondary to infective disease (ex. mononucleosis, tuberculosis, HIV, flogosis of the tonsils, farynx or teeth) or to cancer (ex. lymphomas, thyroid, lung and stomach cancers), thyroid nodules and struma, cysts; uncommon causes should take into account disease such as sarcoidosis, hystiocytosis, ectopic thyroids, esophageal diverticula, arterial aneurisms and cancers. The most easy and accessible non-invasive exams is echography even though only surgical excision might provide a histological diagnosis. US can provide accurate information on the size of the lesion, its echogenicity, its position and relationship to the surrounding structures; duplex and color flow provide information regarding its vascularisation: nevertheless CT and MR represent the gold standard for diagnosis. Carotid Duplex US of the neck showed normal left common carotid artery, right common carotid, right external and internal carotid arteries; left internal carotid and external carotid artery (ECA) were displaced by a 2 cm hypoechogenic and vascularised mass fed by branches of the ECA: it was suspect for a chemodectoma. Even though her familiar anamnesis was negative for paraganglioma (PGL) and a dental procedure had been performed few days before mass appearance, this hypothesis was concordant with the recent increase in blood pressure. This fact and the highly suggestive echographic images—coupled with the higher exposure to X-ray radiation imposed by a CT exam—drove us to perform a diagnostic scintigraphy. Although most of these lesions behave as benign, clinically malignant lesions are seen in 6–12% of cases but they don’t show any histological different features with respect to malignant ones. Hence, malignancy is defined on the basis of local, regional and distant metastasis. Total body scintigraphy using I131-MIBG is used as a screening tool to detect distant additional primary or metastatic lesion in patients. Biochemical assays are routinely employed for the diagnosis of a functioning tumour, irrespectively of symptoms. The usual method is dosage of urinary free catecholamines and their metabolites (vanillyl-mandelic acid and metanephrines) in 24-h urine collection. Patients with CBT, as our case, typically present with a painless mass in the angle of the jaw that may be partially hidden by the sternocleidomastoid muscle; typical manifestations of phaeochromocytoma, as in this case, are evident in 1–3% of patients. Therefore, complete excision of the primitive mass represents at the same time the gold standard for differentiation between benign and malign chemodectomas and treatment of choice. Scintigraphy with 131I-MIBG showed no uptake in the region of the PGL and no evidence of metastases. Urinary catecholamine, metanephrines and vanillyl-mandelic acid were negatives. She was referred for vascular surgery after endovascular embolization of the arterial branches in order to reduce peri-operative bleeding. Histological and immunohistochemical exams documented the presence of neoplastic cells positive for synaptophysin, chromogranin and NSE compatible with a paraganglioma of the carotid body (chemodectoma). The patients was dismissed on day 10th with a diagnosis of community acquired pneumonia and paraganglioma of the carotid body organ. She is alive and her blood pressure has dramatically improved.

An invasion of the field

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 accompanied by compressive atelectasia (treated with a pulmonary drainage) and fractures of seventh, eighth and ninth ribs, hip, bilateral metatarsal and ischemia of right lower extremity with amputation of the right big toe, was admitted to our Division of Internal Medicine for intense, acute dyspnea with dry cough, without fever and chest pain. Vital signs were: temperature 36.7C, heart rate 89 bpm, respiratory rate 15 breaths/min, blood pressure 140/80 mmHg and 97% O2 saturation on room air. Peripheral pulses were normal, no peripheral edema was evidentiated. The patient appeared in moderate respiratory distress. Chest examination showed a reduction of vesicular murmur at the left hemithorax, and ipsilateral mid-basal hypophonia with reduced inspiratory expansion and moist rales. The abdominal examination showed slight distension, mild diffuse tenderness and preservation of bowel sounds. Further, abdominal percussion showed a tympanic sound. Complete blood count showed monocytosis, a mild increase of C-reactive protein. Neoplastic markers and research of viruses and bacteria were negative. A chest X-ray revealed a clouding of the lung in its lower third in relation to moderate pleural effusion with likely underlying bronchopneumonic focus. After an empirical, broad-spectrum antibiotic therapy, a second chest X-ray was performed after 10 days, with no observable modifications. Based on these findings, a thoracic Computed Tomography scan was performed, showing a suspicious left diaphragmatic hernia with bowel loop migration into the left hemithorax. Further, a Magnetic Resonance targeted to the study of the diaphragm, underlined a diaphragmatic hernia with evidence of a 5 cm-hiatus hernia, extending into the left hemithorax for approximately 16 cm in the longitudinal plane, 12 cm in the transversal plane and 18 cm in the antero-posterior plane. Thus, the patient underwent the surgical reduction with plastic of the diaphragmatic hernia through a left thoracotomy access. Currently, the patient is in excellent health condition. Diaphragmatic hernia is a visceral protrusion through diaphragmatic parietal defect. According to the origin, protrusions are classified into congenital and acquired. Among the first ones, we can distinguish between traumatic or surgical injuries. Traumatic diaphragmatic rupture is observed in t 0.2–4% of patient hospitalized for chest and/or abdominal contusion after an injury. Even 10–20% of breaks aren’t detected in the acute phase, being the ‘‘break’’ too small, but getting progressively bigger. Thus, the ‘‘diaphragmatic door’’ may often remain unnoticed and manifest later, even decades after the injury. ‘‘Shortness of breath’’ combined with ‘‘labored or difficult breathing’’ account for 4% of all presenting complaints to the Emergency Departments. Most cases of dyspnea are due to either pulmonary or cardiac diseases. In this case, the exclusion of cardiac and lung causes of dyspnea, patient’s medical history and new imaging techniques led us to consider a traumatic diaphragmatic hernia. Our report emphasizes the importance of taking into consideration in clinical practice a condition such as diaphragmatic hernia in subjects with a personal history of thoracic injury. In our patient, findings of chest X-rays were confused with a stable organization of a traumatic pleuro-pulmonary damage, probably also because there were neither gastrointestinal nor other symptoms prior to our observation. In any case, it is worth noting that the failure to properly diagnose and treat this condition could be fatal, in the case of an enteric strangulation or perforation.

M. Petrarca, F. Pantoli, R. Striuli, P. Giorgini, P. Di Giosia, G. Properzi, C. Ferri Division and School of Internal Medicine, University of L’Aquila, San Salvatore Hospital, L’Aquila, Italy

Dyspnea and weakness in a patient with polyneuropathy: an unexpected finding

A 43-year old man, who quit smoking 10 years ago but formerly smoked about 40 cigarettes per day and had an history of road accident (in 1993) with subsequent left pneumo-hemothorax

C. Pirozzi, G. Bosso, A. De Sena, L. Sacca`, R. Napoli

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Department of Internal Medicine and Cardiovascular Sciences, University Federico II, Naples, Italy

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 A 75 years old man, cigarette smoker, came to our attention for the worsening of dyspnea and asthenia. His medical history showed a recent diagnosis of peripheral polyneuropathy, with motor and sensorial involvement, grade 2 hypertension, hypercholesterolemia. In addition, several years earlier he had undergone right internal carotid endarterectomy. Nine months before the admission to our Department he had been hospitalized for acute dyspnea with angina and discharged with the diagnosis of paroxysmal atrial fibrillation with acute heart failure. During that hospitalization coronary angiography was performed and did not show obstructive atherosclerotic lesions. Four months later he was hospitalized again for leg weakness, heavy asthenia and orthostatic hypotension, diagnosed as autonomic and peripheral polyneuropathy with motor and sensorial involvement. A total body CT scan excluded a paraneoplastic origin of his multiple symptoms and the patient began steroid therapy. At admission, physical examination revealed peripheral pitting edema, jugular venous distention, systolic apical murmur and diastolic murmur on the aortic region. Routine lab tests were normal, except for mild anemia with normal iron depot. The ECG showed sinus rhythm and slightly low voltages in the peripheral leads. Therapy included rosuvastatin and oral prednisone, but no antihypertensive drugs. Clinical presentation suggested heart failure. The transthoracic echocardiogram performed showed concentric left ventricle thickening, severe left atrial enlargement and a normal systolic function (ejection fraction was 50%). There was a restrictive trans-mitral Doppler pattern with end diastolic mitral regurgitation. BNP-nt-Pro-BNP was 2881 ng/L. Therefore, the echocardiographic data strongly suggested, as origin of symptoms, diastolic heart failure with many theoretical possibilities of differential diagnosis: hypertrophic or hypertensive cardiomyopathy, infiltrative cardiomyopathy, constrictive pericarditis, valvular disease, ischemic heart disease. However, echocardiographic exam excluded valvular disease and pericardial involvement, whereas an ischemic origin had been previously excluded by the coronary angiography. On the other hand, hypertrophic cardiomyopathy might be excluded because low ECG voltage are unusual with true left ventricular hypertrophy. Therefore, the diagnostic options were either hypertensive cardiomyopathy or a restrictive cardiomyopathy, particularly an infiltrative cardiomyopathy, most likely amyloidosis, since he had low voltage amplitude at the ECG in peripheral leads. Thus, cardiac MRI was carried out to differentiate between myocardial hypertrophy and cardiac infiltration. The cardiac MRI confirmed increased ventricular mass with thickening also of atrial septal and free wall of right ventricle and revealed a distinct pattern of late gadolinium enhancement, which was distributed over the entire subendocardial circumference, all highly suggestive of cardiac amyloidosis. Given the involvement of other organs such as peripheric and autonomic nervous system, after a negative abdominal fat-pad aspiration, the patient underwent a salivary gland biopsy, that resulted positive for amyloid deposition (positive staining for Rosso Congo). The combination of ECG low voltages, echocardiographic typical abnormalities, cardiac MRI and histologic findings made very likely the diagnosis of cardiac amyloidosis. The level of BNP-nt-Pro-BNP was also consistent with this diagnosis. Since the patient’s showed positive urinary monoclonal kappa chains associated with negative protein electrophoresis we performed also medullar biopsy, that showed a 18% plasmacells infiltrate, excluding the possibility of micromolecular multiple myeloma. So we made diagnosis of AL amyloidosis with cardiac and neurologic involvement. The patients started diuretic therapy with prompt resolution of dyspnea and continued corticosteroid therapy. Cardiac amyloidosis

S227 therapy is based on risk stratification, according to Italian Society of Amyloidosis guidelines (2009), and the patient resulted in the high risk group for the level of BNP-nt-Pro-BNP. Thus, he started the combination therapy, as scheduled by guidelines, with bortezomib and dexamethasone. The patient came back for revaluation 6 months later: his clinical status was improved with regard to the heart failure symptoms and neurological condition. The clinical examination was negative for peripheral edema and jugular distention and transthoracic echocardiography showed a slight reduction of myocardial mass with improved diastolic function at trans-mitral Doppler evaluation (mild diastolic dysfunction). The BNP-nt-Pro-BNP was dramatically reduced.

Differential diagnosis of back pain: a case report L. Postacchini, L. Manfredi, B. Gabrielli, P. Litargini, G. Moroncini, A. Gabrielli Istituto di Clinica Medica, Dipartimento di Scienze Mediche e Chirurgiche, Universita` Politecnica delle Marche, Ancona, Italy AT, a 31 year old Caucasian woman, was referred to our clinic because of severe lumbar pain irradiating to right flank and to iliac fossa just to ipsilateral posterior crural region from 2 weeks; the pain did not respond to non steroidal anti-inflammatory drugs and analgesic treatment. Her medical history was devoid of pathological events and she had not suffered from any repetitive trauma. Physical examination showed pain at abdominal palpation of the right iliac fossa, lumbar spine stiffness and positivity of Lasegue test and Giordan test on the right. Laboratory tests were normal, with exception of increased C reactive protein (1.6 mg/dl) and mild anaemia (Hb 11.2 g/dl). Diagnostic hypotheses: (1) lumbar herniated disc with nerve root compression (2) pyelonephritis or renal colic (3) infectious or neoplastic disease of abdomen, retroperitoneum or pelvis (4) osteolytic lesions secondary to occult neoplasm. Hypotheses

Confirmations

Exclusions

Lumbar herniated Continuous lumbar pain Ovoidal lesion with disc with nerve with Lasegue test’s bone-calcification root positivity; oval findings and with compression expansive formation important contrast at the lateral right reinforcement on extraforaminal lumbar spine RMI. interbody space L2– The neoformation L3 (finding imprinted psoas consistent with muscle and right L2 hernia) on lumbar nerve. No response to spine TC scanning antiinflammatory therapy Pyelonephritis or Typical pain, doubt Absence of bacteriuria, renal colic Giordan test, increase hematuria, pyuria. of the biological Absence of indices of hydronephrosis and inflammation nephrolithiasis at abdominal ultrasonography

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Table continued Hypotheses

Confirmations

Exclusions

Infectious or Mild increase of the Absence of neoplasm neoplastic disease biological indices or salpingitis with of abdomen, of inflammation, functional follicular retroperitoneum pain in the right cysts on or pelvis iliac fossa; 3 cm gynecological (extrauterine cystic lesion of the examination and pregnancy?) right ovary and transvaginal uterine hypoechoic ultrasonography. formation at Pregnancy test abdominal (b-HCG) negativity ultrasonography. Ovoidal lesion imprented psoas muscle on RMI Osteolytic lesions secondary to occult neoplasm

Deep lumbar pain, inflammatory syndrome

Absence of risk factors. Absence of vertebral fractures on lumbar spine TC scanning

Based on radiological findings, a surgical excision of the lesion was performed through a lumbotomic incision. The mass was easily isolated avoiding adjacent muscular or neurovascular injuries. The histological examination demonstrated ‘‘extensive osteoid formation with a fibroblastic area surrounding mature lamellar bone’’, suggesting the diagnosis of myositis ossificans. Myositis ossificans [1] is a benign lesion characterized by heterotopic ossification of soft tissue. Surgical excision led to immediate resolution of patient’s clinical manifestations. Reference 1. Kaplan FS, Glaser DL, Hebela N, et al. Heterotopic ossification. J Am Acad Orthop Surg. 2004;12:116–25.

Un unusually less aggressive disease V. Pretti, T. Kokra, R. Ledda, M. Masala, V. Di Cesare, A. Monni, F. Filigheddu, L. Cuccuru, G. Delitala Istituto di Clinica Medica e Terapia Medica, Azienda OspedalieroUniversitaria, Sassari, Italy A 62 years-old woman, with a history of hypercholesterolemia, type 2 diabetes and hypothyroidism on replacement therapy, was admitted to the our Clinic for a 11 month history of fever, night sweat and weight loss of about 20 kg. She denied a personal and familiar history of cardiovascular, allergic disease and neoplasms. Her clinical history started approximately a year earlier with an hospitalization due to fever and fatigue: the fever resolved with antibiotic therapy cycle and fatigue (anemia with Hb 7.9 g/100 ml) ended with a blood transfusion. After recovery she performed abdomen ultrasonography and total body CT showing 4 spleen hyperechoic and hypodense lesions of 15–63 mm. On admission the patient appeared well; at physical examination presented hepatomegaly of 2 cm and splenomegaly reaching the left iliac crest, without peripheral lymphadenopathies. The blood pressure was normal, heart rate 110 bpm rhythmic, she was eupneic. During the hospitalization the patient had persistently fever above 39C resistant to antibiotics (quinolones, teicoplanin,

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ceftriaxone). In the event of a lymphoproliferative disease blood count and peripheral blood smear were evaluated (normal), and bone marrow aspiration was performed showing a normal finding the hypothesis of an infectious etiology was excluded through blood culture and serology(common aerobic and anaerobic germs, BK, Weil–Felix, Widal–Wright, Chlamydia, Mycoplasma, HBV, HCV, HIV, EBV, CMV, Rickettsia, Ehrlichia, Anaplasma, Bartonella, Leishmania, Aspergillus, Candida). The autoimmune tests were normal as well spleen contrast-enhanced ultrasonography was performed, which evidenced four bulky lesions (59, 64, 65, 70 mm) of unclear origin. The CT scan confirmed the splenic lesions already reported, the largest of which measured about 9 cm in maximum diameter; the other organs had no pathological findings. The gastrointestinal tract was normal at the gastroscopy and colonoscopy. As the fever persisted, in the suspicion of a lymphoma splenectomy was performed. The spleen weighed about 1,050 g and was almost entirely occupied by nodules of confluent whitish with areas of necrosis. Histological examination and immunohistochemical testified to lymphomatous neoplasm composed of a proliferation of intermediate and large cells with clear cytoplasm and atypical polymorphous nuclei, positive for CD45, CD20, CD79a, CD30 and BCL6 and negative for CD45R0, CD3, CD5, Bcl12, CD10, bc11, EMA and ALK. The overall framework put down for a malignant non-Hodgkin’s lymphoma with a large cell diffuse B phenotype. Immediately after the splenectomy the fever disappeared and the patient slowly recovered. She is currently fairly well, making repeated cycles of chemotherapy. The relevancy of this case is not based on the conclusive diagnosis, quite expected, but mainly on the indolent behavior of this cancer, classified in the literature as among the aggressive lymphomas.

Apparently unexplained very high levels of d-dimer in a patient with addisonism and erectile dysfunction G. Puccia, A. Campagna, C. Cilia, B. Stancanelli, L.S. Malatino Clinica Medica Universita` di Catania, Catania, Italy A 60 year-old man presented at the Emergency Department with symptoms of debility associated with occasional dizziness. Oxygen saturation was normal and there was no cardiac and respiratory rate abnormalities. Sitting blood pressure was 110/60 mmHg, plasma sodium and potassium, B-Type Natriuretic Peptide and Troponin-I were unremarkable, but very high levels ([7,000 ng/ml) of D-dimer were also detected. The patient was admitted to the Division of Internal Medicine for diagnosing the nature of his symptoms. The patient had no history of diabetes, dyslipidemia, hypertension and obesity. Erectile dysfunction occurred in the last 12 months. Normal leg pulses were detected bilaterally. Taking into account high levels of D-Dimer, the lack of chest pain, dyspnea and other risk factors for pulmonary embolism (deep venous thrombosis, recent surgery) made priority to carry out chest CT-scan rather low. Meanwhile, endocrinological work-up demonstrated very low levels of serum TSH, FT3, FT4, FSH, LH, ACTH, Cortisol and Testosterone, thus suggesting that debility, dizziness and erectile dysfunction could have been related to a pituitary disease determining hypopituitarism. At this stage, the very high levels of D-dimer remained still unexplained. We assigned high priority to evaluate pituitary gland by Computed Tomography (CT), while a CT scan of aorta to explore the possibility of asymptomatic aortic dissection was postponed. Surprisingly, Brain CT-scan showed a giant thrombosed intracellar aneurysm of right internal carotid (24 9 18 9 11 mm), without signs of hydrocephalus. Therefore, hypopituitarism was due to mass effect of an intracellular giant, thrombosed aneurysm on the pituitary gland, also determining

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 the large increase in D-dimer levels. The patient was started on steroid and L-Thyroxine supplementation, and debility progressively disappeared within 4 weeks. Spontaneous thrombosis in a giant intracellular internal carotid aneurysm is a unique feature of the present case-report. Hypopituitarism would be expected to remain permanent, thereby implying chronic hormone supplementation. Endovascular repair of intracranial aneurysm would be the treatment of choice, but the patient is still doubtful to accept undergoing this procedure because he is symptomless while taking hormone supplementation and is fearful about potential complications of endovascular repair. In conclusion, the main features of this case-report would underscore: (1) the possibility that hypopituitarism may be the consequence, although rarely, of mass effect of a giant intracellular aneurysm; (2) the need to find out anyway the reason for an apparently unexplained large increase in serum levels of D-dimer.

When an anemia puts you ‘‘ALI’’ E. Renna, L. Catalano, F. Pappagallo, A. Perrone Dipartimento di Clinica Medica, Immunologia e Malattie Infettive Sezione di Medicina Interna Universita` di Bari, Bari, Italy In this report we describe the case of 61 year-old man that came to our attention for exercise induced dyspnea, in a subject with a severe anemic state (Hb 5.5 mg/dl, MCV 70 fl). In his clinical history the patient reported a diagnosis of a depressive syndrome ongoing for about 10 years and for the past 4 months nausea, emesis, lacking of appetite, loss of weight (around 10 kg). Since a few weeks prior to the admission to the hospital the patient started to suffer from a worsening exercise dyspnea and palpitation. Upon physical examination the patient was found pale, tachycardic, normotensive, slightly tachypneic with a vesicular murmur highly reduced in the lung bases. Some hematochemical exams reported altered values: PCR 10.30 mg/dl (normal range 0–0.5 mg/dl); Ferritina 2,145 ng/ml (normal range 10–370 ng/ml); VES 42 mm/h (normal range 1–20 mm/l); Fibrinogen 1,014 mg/dl (normal range 170–410); D-dimers 1422 ng/ml (normal range \ 150 ng/ml); Creatinine 1,80 mg/dl (normal range 0.6–1.2 ng/ml); Cardiac Troponin I 0.19 ng/ml (normal range 0–0.07 ng/ml). An hemogasanalysis conducted without subministration of oxygen showed the following values: pH 7.49; pCO2 27 mmHg; pO2 59 mmHg; SO2 96%; HCO3- 20.6 mmol/L. An electrocardiogram showed a sinus tachycardia with a heart rate of 120 bpm. A chest X-ray (CXR) showed a small basal pleural effusion. Therefore the patient underwent a transfusion of 2 units of red blood cells. After 5 h the patient developed a severe hypertensive crisis (BP 260/160 mmHg) associated with an acute respiratory failure (SO2 86%, PO2 55 mmHg, PCO2 37 mmHg) that required a non-invasive ventilatory support (NIV) with a C-pap. A second CXR showed signs of vascular congestion of the pulmonary circle with a bilateral pleural effusion and dishomogeneous opacities in the lower right lung. Following the heightening of the D-dimers (3,149 ng/ml) and the Cardiac Troponin I (0.86 ng/ml) and considered the impossibility of executing an angio-CT because of the kidney failure, the patient underwent a Perfusion lung scintigraphy that came out positive for pulmonary embolism with a normal cardiac ECHO. Following those findings a therapy with low molecular weight heparin (LMWH) was started. In a few hours the clinical conditions of the patients started to get back to normal. In the following days, having found a PSA value of 696 ng/ml (n.v. 0–4 ng/ml) a total body CTscan was executed which showed a discrete posterior basilar pleural effusion much more evident in the left lung without any infiltrative lesions; the prostate gland had

S229 a larger volume with a dishomogeneous aspect along with osteolytic and osteoblastic secondary lesions in all bone segments. The histological exam of the gland described a poorly differentiated adenocarcinoma. The anomalous finding of a hypertensive crisis associated with pulmonary embolism, instead of a far more expected acute pulmonary edema made us reconsider the transfusion of RBC as the starting cause of the acute respiratory failure. We hypotized as a valid explanation of this case the TRALI event (Transfusion Related Lung Injury) defined by the National Heart Lung and Blood Institute (NHLBI) as the onset of an acute lung injury (ALI) within 6 h from the transfusion of one or more blood components without any other risk factor for ALI with symptoms disappearing in 48 to 96 h, after a proper ventilatory and hemodynamic support was initiated with a full lung function recovery. The clinical onset of the TRALI is similar to any other causes of lung failure so it is a diagnosis of exclusion. The pathogenetic mechanism is still unknown but there appears to be either an intense immunological reaction (conducted by anti granulocytes neutrophils antibodies) or a non-immune reaction (through transfunded lipids activating the leucocytes) which leads ultimately to an alveolar damage. The incidence rates for this event is between 1:450 and 1:550,000 transfunded patients varying according to the hemoderivates used (respectively platelet concentrated and red blood cells). The TRALI event nowadays has taken the place of the posttransfusional hemolytic reaction as the major cause of transfusioncorrelated deaths.

HIV/HCV co-infected patient harbouring an unusual pattern of cardiovascular risk factors A. Renzi1, A. D’Angelo1, F. Vinci1, P. Coletta 1, E. Arcovio2, R. Giura3, E. Grieco1, N. Vo Hong1, O. Raimo1, A. Castello1, G. Barbarossa1, F. Cantoresi1, A. Santoro2, C. Durante1, M. Colotto1 1

Department of Internal Medicine and Medical Specialties; Department of Neurological Science, Neurosurgery; 3Emergency Department Policlinico Umberto I, University of Rome Sapienza, Rome, Italy

2

A 38-year old woman was referred to Lipid Outpatient Clinic of our Department for mixed dyslipidemia and amenorrhea. Her clinical history was remarkable for illicit injective drugs abuse and HIV-HCV co-infection from the age of 24. She was on current treatment with HAART (Highly Active Antiretroviral Therapy; i.e. tenofovir plus emtricitabine plus fosamprenavir/ritonavir). Her family history was positive for severe hypercholesterolemia in her mother. Her clinical examination showed a BMI of 24 kg/m2, a tendon xanthoma in the left hand, sweating of the palms, accentuated prognatism and macroglossia; when questioned the patient referred a change in shoe size over the past 5 years and the impossibility to wear her wedding ring. A picture taken when the patient was 25 years old confirmed the present enlargement of face’s bones. Before starting HAART, lipid profile showed a total cholesterol (TC) level of 419 mg/dl, with LDL cholesterol (LDL-C) level of 353 mg/ dl, HDL cholesterol (HDL-C) of 32 mg/dl, triglycerides (TG) of 171 mg/dl. According to current guidelines a diagnosis of heterozygous familial hypercholesterolemia (FH) was made. A clinical suspect of acromegaly was confirmed by the dosage of GH and IGF-1 levels, respectively 43.3 ng/ml (n.v. 0.1–10 ng/ml) and 713 ng/ml (n.v 144–360 ng/ml). A pituitary MRI showed a huge sellar macroadenoma of 27 9 19 mm with signs of optic chiasm compression (Fig. 1). The optic way compression was confirmed by a computed examination of visual

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field that showed a marked bitemporal hemianopsia (Fig. 2). Transsphenoidal microsurgical removal of macroadenoma was performed; few days after intervention a marked improvement in patient’s visual field was observed by a new computed examination (Fig. 2). To our knowledge this is the second case of association of acromegaly and HIV/HCV infection and presents several points of interest:

A rare disease with an unusual clinical presentation: pulmonary epithelioid hemangioendothelioma

1. A mixed dyslipidemia may hide several conditions, and, even if rare, they can be associated in the same patient, and thus must be accurately investigated by the physician. 2. All FH, acromegaly, HIV/HCV infection and the HAART markedly influence CV risk by affecting, at different level, lipid and glycemic profiles and blood pressure, thus accelerating the development of the atherosclerotic process. This patient harboring such unusual conditions, despite her age, is at very high cardiovascular risk. 3. The decision to make a surgical intervention was challenging because of the potential need for a substitutive therapy with corticosteroid after the removal of pituitary macroadenoma; this therapy could negatively affect the clinical course of both HIV and HCV chronic infection. The big size of adenoma and the high risk of progressive blindness as shown by visual field examination were the definitive considerations to make the therapeutic decision.

Case report: In November 2010 a 39-year-old woman noted the onset of a painful swelling in the left axillary cavity, covered with erythematous skin and associated with episodes of mild fever (Tmax 37.8C). She has family history of breast cancer and no prior medical history. Laboratory tests were within normal limits. The breast ultrasound and RX-mammography showed a well-defined margins nodule in the upper quadrant of left breast (11 mm [) and echodoppler showed the presence of thrombosis of a superficial axillary vein. The young woman was taking oestroprogestative oral contraceptives who have been suspended. The screening tests for thrombophilia were negative. Therapy with low molecular weight heparin was started, without benefit. Histological examination of the biopsy of breast lesion revealed a fibroadenoma. A subsequent angiocomputed tomography confirmed the presence of a superficial venous thrombosis in the axillary and collaterally showed the presence of lung nodules. According to these findings, whole body computed tomography was performed with the following pathological findings: multiple bilateral pulmonary nodules suspected for sarcoidosis or miliary tuberculosis (maximum diameter 1 cm), multiple liver hemangiomas, and aneurism of the splenic artery (22 mm), in addition to the thrombosis of a superficial axillary vein. In February 2011 the patient was admitted to our division for the first time to further evaluation. The tumor markers were rigourously normal. We noted that some lung nodules (maximum diameter 3 mm) were present in a computed tomography scan of the chest that the patient had done in 2001. We submitted the patient to the thoracic surgeon to perform a thoracoscopy. Video-assisted thoracoscopy showed numerous yellowish pulmonary nodules of hard consistency, some of which emerging to the visceral pleura. Diagnosis was made by pulmonary wedge resection of a nodule located in the right upper lobe and epithelioid hemangioendothelioma was revealed. The immunostaining patterns showed a positivity for CD 34 and CD 31 and a negativity for actine ML, desmine, pS-100, HMb45, cytokeratin AE1–3, EMA. Considering extensive pleuro-pulmonary involvement, and also the possible location at the axillary vein, chemotherapy treatment was proposed. Currently the patient is receiving a taxane-based chemotherapy in another oncology center. Since the beginning of treatment, superficial phlebitis has gradually improved. Discussion: This case report highlights some aspects of a rare disease: epithelioid hemangioendothelioma. In particular pulmonary epithelioid hemangioendothelioma is a rare neoplasm of vascular origin with higher prevalence among women; fewer than 100 cases are reported in the literature. The uncommon clinical presentation with venous thrombosis of a superficial axillary vein in a young woman in an apparent state of health, the presence of mild fever, the breast nodule and the suggestive radiographic picture allowed to different diagnostic hypotheses (thrombophilia, breast cancer, infectious diseases) that were gradually excluded up to the unexpected final diagnosis. Because of the rarity of this condition, there is no standard treatment of choice. Despite having an intermediate malignant, potential extensive pulmonary involvement and systemic spread have been described. Surgical and/or chemotherapeutic options have to be evaluated depending on intrathoracic tumor spread and systemic metastases. Probably the patient had the disease already in 2001, when a few lung micronodules were detected, consistent with intermediate malignant potential of the disease.

Fig. 1

Fig. 2

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M.A. Ricciotti, G. Cristina, R. Gareri, L. Cifaldi U.O.C. Oncologia Medica, Azienda USL RM G, Ospedale Parodi Delfino Colleferro, Rome, Italy

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 However, at present the disease has become symptomatic with an extensive pleuro-pulmonary involvement, so the ‘‘wait and see’’ approach and surgery were excluded towards a chemotherapy treatment which obtained an immediate clinical benefit on axillary thrombosis.

An uncommon manifestation of metastatic lung cancer disease-progression M.A. Ricciotti, G. Cristina, R. Gareri, L. Cifaldi U.O.C. Oncologia Medica, Azienda USL RM G, Ospedale Parodi Delfino Colleferro, Rome, Italy A 72-year-old woman, smoker, with no prior malignant disease history, was admitted because of cephalgia, dyspnea and fatigue; her performance status (WHO) was 2. According to clinical conditions, whole body computed tomography, bone gammagraphy, brain magnetic resonance and bilateral mammography were performed, with the following pathological findings: numerous lesions with surrounding oedema in both cerebral hemispheres, multiple bony metastases, a lung 30 mm left lower lobe lesion, which infiltrated the inferior pulmonary artery and extended along the posterior wall of the superior lobar bronchus. No other lesions were detected and the tumor markers were also rigorously normal. Puncture-aspiration biopsy of lung nodule was done and adenocarcinoma was revealed. The immunohistochemical examination was not performed because poor biopsy material available. Spreading of the disease was consistent with metastatic lung cancer. The patient was scheduled for pan-encephalic radiating treatment (40 Gy in 4 weeks), followed by chemotherapy with Gemcitabine (Gemzar, Lilly) 1,000 mg/m2 day 1, 8, 15 every 28 days, for 4 cycles, in combination with zoledronic acid (Zometa, Novartis) 4 mg day 1 every 28 days. The treatment was well tolerated and at the end of chemotherapy the patient referred an improved general condition (performance status WHO 1) but also a right axillary rapidly growing painless, movable mass. The re-staging of the disease with the whole body computed tomography showed lung stable disease, complete regression of encephalic metastasis and the presence of 20 mm right axillary lymphadenopathy. In addition, an ultrasound examination of the breasts and axilae was taken. It revealed an oval, well-defined mass between in the upper quadrants (15 9 5 mm) of the right breast and three lymph nodes of 20, 9 and 7 mm diameters in the right axils. A fine needle aspiration biopsy was performed revealing a malignant carcinoma. Following this report, in suspicion of breast cancer, decision-making was to undertake an excisional biopsy to ensure adequate clearance. Histological examination unexpectedly demonstrated metastatic nodule from lung adenocarcinoma. This morphological evidence was supported by immunohistochemical study. The immunostaining patterns showed a positivity for CK7, TTF1 and a negativity for CK20, Er, PgR and actine ML. The combination of cytokeratin 7 and cytokeratin 20 is useful in categorising carcinomas. Breast cancer is typically cytokeratin 7+ and cytokeratin 20-. Oestrogen receptor is expressed in 80% and progesterone receptor in 60% of mammary carcinomas. TTF-1 is expressed by about 75% of pulmonary adenocarcinomas and, apart from carcinomas of the lung and thyroid, it is rarely seen in other carcinomas. As consequence of the pulmonary disease progression a second line treatment with weekly docetaxel (Taxotere Sanofi-aventis) was scheduled. After 4 weeks the chemotherapy was interrupted by a gradual deterioration in the overall condition of the patient. Discussion: The case report shows an uncommon progression-disease of metastatic lung adenocarcinoma after the first-line chemotherapy.

S231 Breast metastasis from extra-mammary malignancy is rare. Based on the literature an incidence of 0.4–1.3% is reported. The primary malignancies most commonly metastasizing to the breast are leukemia–lymphoma and malignant melanoma. Accurate diagnosis is important to ensure appropriate management. The diagnosis may be straightforward if there is a clinical history of extramammary malignancy, particularly if sections are available for comparison. Both the histological diagnosis and study of spread disease are important for choosing the best possible treatment for the patient. Accurate differentiation of metastatic from primary carcinoma is of crucial importance because the treatment and prognosis differ significantly; the overall prognosis of patients with metastatic solid tumour to the breast is poor with more than 80% dying within 1 year.

Optic neuritis in patient with rheumatoid arthritis treated with TNFa antagonists V.C. Rollo, A. Matarangolo, G. D’Alessandro Clinica Medica Azienda Ospedaliera Universitaria, Ospedali Riuniti, Foggia, Centro studio malattie apparato osteoarticolare ed immunoproliferative, Foggia, Italy Objective: Rheumatoid arthritis (RA) is a common disease which affects young people and last their whole life [1]. Treatment of this pathology has been totally revolutionized during last 15 years, especially after the development of new promising classes of antirheumatic agents, such as anti-tumour necrosis factor alpha (anti-TNFa) therapy, well known as biological agents [2]. Many patients suffering from rheumatic disease have been successfully treated, but several reports describe the ex novo development or exacerbation of pre-existent demyelinating disorders, as optic neuritis (ON), Multiple Sclerosis (MS) and Guillain–Barre´ syndrome (GBS), after the treatment with TNFa antagonists [3]. Above all the use of infliximab is associated with two possible forms of optic neuritis, retrobulbar optic neuritis and bilateral anterior toxic optic neuropathy. Methods: We describe a case of TNF-alpha antagonist-induced optic neuritis in a young women. Result: A 57 year old women, suffering from rheumatoid arthritis, was not responder to conventional therapy, started at the first clinical evaluation. We decided to treat her with Infliximab, an anti TNFa. We observed a sudden improvement of clinical conditions but few months later she developed an acute visual loss of the eye left during the Infliximab infusion. Her MRI showed ON with papilledema. The treatment was immediately suspended until the next exacerbation of the disease, which was therefore treated with Etanercept, but only for 3 months for inefficacy. Endly Rituximab was then introduced with excellent clinical results. Conclusion: In our opinion, it’s important not to forget the likelihood of the development of optic neuritis during treatment with infliximab and in this case we’ve found helpful starting Rituximab therapy. References 1. Wiedmann MW, Mo¨ssner J, Baerwald C, Pierer M. TNF alpha inhibition as treatment modality for certain rheumatologic and gastrointestinal diseases. Endocr Metab Immune Disord Drug Targets. 2009;9(3):295–314 2. Fantini F. New drugs and treatment strategies for rheumatoid arthritis. Recent Prog Med. 2003;94(9):361–79 3. Simsek I, Erdem H, Pay S, Sobaci G, Dinc A. Optic neuritis occurring with anti-tumour necrosis factor a therapy. Ann Rheum Dis. 2007;66(9):1255–8

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S232 Prolonged aPTT in a patient with biliary cirrhosis P. Rondelli1, G. Lupattelli1, A. Elmo1, F. Crisanti1, S. De Vuono1, M.R. Mannarino1, P. Gresele2, E. Mannarino1

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Reference 1. Huth-Ku¨hne A, Baudo F, Collins P, et al. International recommendations on the diagnosis and treatment of patients with acquired hemophilia A. Haematologica. 2009;94:566–75

1 Medicina Interna Angiologia e Malattie da Arteriosclerosi, Dip. Medicina Clinica e Sperimentale; 2Medicina Interna e Vascolare, Dip. Medicina Interna, Universita` di Perugia, Perugia, Italy

Carcinoma of unknown primary tumor (CUP) in a young man A 61 years old woman was admitted to our Department with epistaxis and macro-hematuria. On examination, the patient was restless, confused (Glasgow coma scale 9), with flexion deformities of the fingers, sclerodactyly furrows around the mouth perpendicular to the lips and the lips were thin; also splenomegaly and ascites were present; blood pressure 90/70 mmHg, heart rate 108 bpm, SpO2 90%, temperature 38.0C. Physical examination of the chest revealed tachypnea and bibasilar endinspiratory dry crackles. Patient’s medical history started on 2003 with a diagnosis of systemic sclerosis with pulmonary fibrosis and rheumatoid arthritis; on 2009 primary biliary cirrhosis with ascites and esophageal varices was also diagnosed; actual treatments were etanercept, prednisone, atenolol, sildenafil, and ursodeoxycholic acid. At the admission, blood chemistry showed microcytic anemia (Hb 7.6 g/dl), increased erythrocyte sedimentation rate and C-reactive protein, neutrophil leucocytosis, hypoalbuminemia, hyperbilirubinemia, hyperammonemia, elevated ALP and cGT, normal platelet count and fibrinogen. Urine examination showed erythrocytes, leukocytes and bacteria. Coagulation studies revealed a normal prothrombin time and international normalized ratio, with a prolonged activated partial thromboplastin time of 92.3 s (normal 26.7–38.0) with previous evidence of this parameter as normal. The abdomen ultrasonography confirmed hepatic cirrhosis, splenomegaly and ascites. CT scan of the brain did not show any recent ischemic or haemorrhagic lesion. This clinical picture, consistent with hepatic encephalopathy triggered by blood loss and urinary tract infection, was initially treated with lactulose, paromomycin, packed red blood cell, fresh frozen plasma and broad spectrum antibiotics (cephalosporin and imipenem). Consciousness improved, while macro-hematuria and epistaxis persisted, due to the prolonged aPTT. The differential diagnosis of the bleeding could be coherent with sepsis with disseminated intravascular coagulation (DIC) and, due to the autoimmunity anamnesis, the presence of lupus anticoagulant (LAC) or of coagulation factor inhibitors. The hepatic coagulopathy was unlikely because it is responsible for a prolonged serum prothrombin time due reduced synthesis of vitamin K-dependent factors; also DIC could be reasonably excluded because fibrinogen and platelet count were normal. Then, a mixing study was performed: the addition of normal plasma to patient’s plasma corrected aPTT only partially, a pattern consistent both with LAC and with acquired hemophilia. The presence of an inhibitor of coagulation was confirmed by quantitative assays which revealed a severe reduction of factor VIII activity (0.41%, vn 50–150) and the presence of factor VIII inhibitor (7.5 U Bethesda). The activity of LAC was slightly positive. Thus the conclusive diagnosis was acquired Hemophilia A, due to the presence of factor VIII inhibitor in a patient with a primary biliary cirrhosis and scleroderma overlap syndrome. The patient was treated methylprednisolone 80 mg/die and rFVIIa 90 lg/kg every 4 h until macro-hematuria and epistaxis stopped. This disease is extremely rare, with a frequency of 1.5 cases per million/year [1] and is associated with an high rate of mortality; in up to 50% of patients an underlying medical condition including autoimmune diseases, solid tumors, lymphoproliferative malignancies is identified.

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A. Russo, M. Villiva`, A. Notturni, A. Vena, P. Marinelli, V. Fontana, L. Borgognoni, A. Paris, F. Vaccaro, P. Palange Sapienza Universita` di Roma, Policlinico Umberto I, Dipartimento di Sanita` Pubblica e Malattie Infettive, UOC Medicina Interna I, Roma, Italy A 39-years-old man was admitted to our ward for the appearance of deep vein thrombosis which was diagnosed 2 months before admission when occurred an acute pulmonary embolism, for which the patient was treated with oral anticoagulant therapy. Case history revealed he never smoked and he never suffered of any disease. Upon the admission, physical examination was normal except for signs of inflammation at both upper and lower extremities. Laboratory tests revealed only increase of D-dimer (14.134 ng/ml) and inflammatory index (ESR 70 mm/h; CRP 30.438 l/l). The signs of thrombosis were diffuse to all limbs with a resistance to warfarin treatment; moreover, we decided to investigate the causes of this alteration: genetic, immunologic and neoplastic etiologies were considered. As first, we performed genetic tests for coagulation factors. The results showed normal Leiden’s V Factor, Prothrombin, MTHFR, C and S Protein; Homocystein was 17,6 lmol/l. Autoimmune tests (ANA, ENA, LAC, anticardiolipin and anti b2 glycoprotein) were normal too. In order to detect the presence of malignancy we performed total body CT and MR, gastroscopy, colonoscopy, ultrasonography of prostate, bladder, testis, heart, thyroid. All investigations didn’t show any sign of malignancy. After 2 months of hospitalization, we detected the appearance of cervical lymphadenopathy, which was absent at the admission. Considering the negativity of previous tests we decided to perform PET CT with 18F-FTG that showed many cervical, mediastinal and abdominal lymphadenopathies; only cervical were metabolically active. So we decided to perform biopsy of the lymph node; the histological exam revealed the presence of metastatic, poorly differentiated, cancer. The dosage of tumor markers showed increase of CEA, CA 19.9; CA125; CA 15.3; chromogranin and NSE. Considering these findings, the diagnosis of carcinoma of unknown primary tumor was made and anticoagulant therapy with Fondaparinux and two cycles of empiric chemotherapy was started. One month after discharge the patients was again admitted in hospital for the onset of intense abdominal pain. He underwent urgent surgery which showed massive bowel infarction. The patient died few days after and autopsy didn’t find any solid malignancy. Carcinoma of unknown primary tumors (CUP) is a biopsy-proven malignancy in which the anatomical origin of the tumor cannot be identified from the patient history, physical examination, laboratory testing, chest radiographs, computed tomography of the chest, abdomen and pelvis, mammography, even in the post-mortem examination. CUP is present in 0.5–9% of patients with malignant neoplasms; however, only 20–27% of primary sites are identified before the patients die. Some studies have reported that although the

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median survival time of patients with CUP is less than 1 year, if the primary site is identified and specific therapy started, the survival time can be increased [1]. Reference 1. Juweid ME, Cheson BD. Positron-emission tomography and assessment of cancer therapy. N Engl J Med. 2006;354:496–507

Exertional rhabdomyolysis: a case report A. Sacchi, A.G. Falchi, G. Ferrari, C. Malagola, C. Sacco, L. Veronese, C. Muggia, G. Perani Clinica Medica II Fondazione IRCCS Policlinico San Matteo, Pavia, Italy S.S., 35 years old, male. He entered the Ward for worsening myalgias, appeared about 48 h before admission, starting from lower limbs and subsequently raising up to the shoulder blades, causing limitation in movement. At home the patient had been taking diclofenac and thiocolchicoside, with no benefit. At the Emergency relevant elevation of CPK (85,000 mU/mL), LDH (10,600 mU/mL) and transaminase (GOT 2,600 mU/ml, GPT 640 mU/mL) was registered. The patient reported a history of drug abuse between the age of 14 and 28 and a current daily intake of inhaled cannabinoids. At the age of 18 he underwent hospitalization due to acute HBV hepatitis with HCVpositive feedback, which was never treated. About 3 weeks before admission he assumed amoxicillin/clavulanic ac (2 g daily for 7 days) and nimesulide (500 mg daily for 3 days, then lower doses for 7 days). The patient reported strong exercise (cycling) the day before the onset of myalgia, though comparable to the training sessions he normally carried out weekly. In our division he underwent a massive hydration therapy (up to 16 L/ day) with osmotic diuretic (mannitol 125 mL 9 3/die) and low doses of sodium bicarbonate to alkalize urine. CPK gradually increased up to a peak of 417,900 mU/mL in day 2 of hospitalization. The same course was registered for LDH (peak 20,171 mU/mL in day 2). The values of transaminases followed a different curve, reaching a peak on day 4 (GOT 5,660 mU/mL and GPT 1,700 mU/mL, respectively). As both the GOT/GPT ratio and the other liver function tests remained stable, such phenomenon was interpreted as secondary exclusively to muscle cytolysis. At the same time severe myoglobinuria (333 ng/mL at admission) was recorded. The laboratory parameters have been gradually improving until an almost complete normalization at discharge. As regards the subjective symptoms, they had already regressed on day 2 and hydration had been slowly reduced. No changes were registered in renal function and acid–base balance. Table 1 Laboratory parameters variation in time 3/5

4/5

5/5

6/5

7/5

13/5

23/5 135

CPK (mU/mL)

85,340

417,900

361,600

265,400

109,200

2,639

GOT/GPT (mU/mL)

2,631/ 647

4,917/ 1,163

5,286/ 1,382

5,664/ 1,964

3,462/ 1,470

202/491 56/108

LDH (mU/mL)

10,635

20,171

15,879

10,319

3,962

666

387

A toxic etiology for massive rhabdomyolysis was ruled out because the time frame for nimesulide was not compatible with the onset and blood and urine sampling for complete drug-abuse panel (including synthetic cannabinoids) resulted in a positive response only to natural

cannabinoids, consistent with the history. Occasional intake of food toxins was excluded anamnestically (no other case of rhabdomyolysis in the family), as well as a possible genetic component (the only episode in adult patients, family history reconstructed and negative). Virological tests only pointed out high HCV-RNA viral load (4,158,000 copies/mL) and a previous infection by HSV-1. Considering the acuity, muscle biopsy was not performed. In absence of alternative hypothesis, we consider exhausting exercise the most likely explanation for massive rhabdomyolysis. Although it was not possible to identify the trigger that had led to massive cell lysis, rhabdomyolysis following strenuous exertion had been first reported in military trainees in 1945, and much of the subsequent literature has focused on this population. The pathophysiology of this syndrome remains unknown, however it seems that lower rates of complications are related to exertional rhabdomyolysis than other causes.

Eosinophilic gastroenteritis: role of ultrasonography in the diagnosis and follow-up R. Salvatore, A. Savino, C. Cecamore, P. Pelliccia, F. Chiarelli Clinica Pediatrica, Ospedale Clinicizzato SS.Annunziata, Chieti, Italy We report a case of a adolescent with a 3 weeks history of severe epigastric pain, nausea and vomiting. His medical history was significant only for an hospitalization at the age of 7 years, when he presented a laryngospasm; skin prick tests were positive to Dermatophagoides pteronyssinus. His father also suffered of allergic disorders (allergy to pollens). Clinical examination was unremarkable, except for tenderness in the left abdominal quadrant. A surgical evaluation was performed, with no indication of an acute surgical abdomen or appendicitis. The total leukocyte count was increased with an high percentage of eosinophils. Because of persistent severe abdominal pain an ultrasonographic evaluation was performed, demonstrating an increased wall thickness of the pylorus affecting the muscle layer and an increased bowel wall thickness of the terminal ileum. Moreover it showed moderate ascites in the pelvis, in the Morrison’s hollow and on the bladder. A computed tomography (CT) scan of the abdomen confirmed increased wall bowel thickness of the jejunum and of the ileum, and the presence of fluid in the pelvis. Some lymph nodes were detected in the mesenteric space, indicating inflammation. Paracentesis disclosed exudative effusion with high-level of eosinophils. To confirm full-thickness involvement, a biopsy of the gastric and duodenal wall was performed. Microscopic examination of biopsy specimens showed moderately eosinophilic infiltration of the duodenal and gastric mucosa, with serosal involvement. Upon these findings, eosinophilic gastroenteritis was diagnosed [1–3] and prednisone therapy was immediately started. The patient achieved a complete clinical and pathologic remission after 3 weeks of steroid course. He achieved a complete clinical and pathologic remission after 3 weeks of steroid course. Sonography showed regression of the bowel wall thickness, and the total reabsorption of the ascitic fluid in the pelvis [4, 5]. References 1. Khan S. Eosinophilic gastroenteritis. Best Pract Res Clin Gastrenterol. 2005;19(2):177–98 2. Oh HE, Chetty R. Eosinophilic gastroenteritis: a review. J Gastroenterol. 2008;43(10):741–50

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S234 3. Chen MJ, Chu CH, Lin SC, Shih SC, Wang TE. Eosinophlic gastroenteritis: clinical experience with 15 patients. World J Gastroenterol. 2003;9(12):2813–6 4. Maroy B. Nonmucosal eosinophilic gastroenteritis: sonographic appearance at presentation and during follow-up of response to prednisone therapy. J Clin Ultrasound. 1998;26:483–6 5. Buljevac M, Urek MC, Stoos-Veic´ T. Sonography in diagnosis and follow-up of serosal eosinophilic gastroenteritis treated with corticosteroid. J Clin Ultrasound. 2005;33(1):43–6

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 1,485 kcal in divided meals with 49.5% carbohydrates, 22.6% proteins and 27.9% fats. Over the next 7 days no episodes of encephalopathy or metabolic acidosis have occurred; stool cultures, Widal reaction, D-lactic acid in serum and urine were negative and the patient was discharged with antibiotics and probiotics (rifaximine and Lactobacillus GG). No more attacks happened in six months follow-up.

Persistent haematuria in an elderly man E. Satta, L. Testoni, E. Dalla Nora, G. Zuliani

D-Lactic acidosis 25 years after bariatric surgery due to salmonella enteritidis: a case report

Sezione di Medicina Interna, Gerontologia e Nutrizione clinica Universita` di Ferrara, Ferrara, Italy

L. Sardo, A. Gigante, M.L. Gasperini, A. Molinaro, O. Riggio, A. Amoroso

A ‘‘previously healthy’’ 98 year-old man came to our ward complaining persistent haematuria not associated to other symptoms. Over the last 5 days his primary care physician advised antibiotic treatment for suspect urinary infection without any benefit. The patient had a medical history of arterial hypertension in good pharmacologic control (torasemide), asymptomatic hyperuricemia, and previous not complicated surgery for inguinal hernia; he was not taking anticoagulants or nonsteroidal anti-inflammatory drugs. At admission to hospital, the patient looked quite pale and poorly cooperative, but orientation to time and place were good. He was afebrile and vital signs were stable. Pulmonary and cardiovascular examination were normal. There was evidence of clots on urethral meatus. Initial laboratory tests showed normocytic and normochromic anemia (haemoglobin 8.8 g/dl, mean corpuscular volume 100 fl), mild thrombocytopenia, prolonged aPTT (ratio 2.2) with normal PT-INR. In order to investigating haematuria we ask for ultrasound examination of the urinary tract (no features of pyelocalyceal ectasia, normal kidneys size, no endoluminal bladder lesion), and urological counselling (suspected urethral bleeding). No urinary tract infections was found. During the 4th day of hospitalization patient’s condition quickly impaired because of onset of coma with flaccid left limbs paresis and flattening of the nasolabial fold. Brain CT scan showed a massive hematoma of right occipital and temporal lobe with irruption on ventricular compartment; moreover, a large hypo dense lesion suggestive for brain tumor was observed in the same hemisphere. No advice to hematoma evacuation was suggested by the Neurosurgeon. Because of the bleeding diathesis with normal PT-INR values and platelet count, suspicion of acquired haemophilia (AHA) was made and additional coagulation tests were performed. Although treatment with rFVII and immunosuppressive therapy are recommended in these cases, very advanced age, poor prognosis related to acute intracranial bleeding, and suspicion of cerebral neoplasy derived us to start only general supportive care. Patient’s condition further get worse because of hematemesis, persistence of haematuria, and severe anemia requiring blood transfusion. Death occurred 10 days after admission. Coagulation tests confirmed the diagnosis of AHA (activated partial thromboplastin time abnormal even after 1:1 mixing assay, presence of factor VIII inhibitor) Although in the elderly AHA is often an idiopathic condition, we cannot rule out the hypothesis that in our patients it might be secondary intracranial neoplasia as previously reported.

Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy A 51 year old Caucasian woman was admitted in emergency department with an acute confusional state characterized by disorientation, weakness, nausea, dehydration, blurred vision, slurred speech appearing drunk. Her medical history was significant for a jejuno-ileal bypass procedure in 1985 for obesity; 9 years later she was hospitalized for neurologic syndrome probably due to bacterial overgrowth. Since she beginning therapy with rifaximine, 2 weeks every month until hospitalization. On admission, her temperature was 37.6C, blood pressure 120/80 mmHg, pulse 79 bpm. Physical examination was negative except for mild and diffuse abdominal pain with no organomegaly or ascites. Arterial blood gas analysis showed normocloremic metabolic acidosis with increased anion gap (pO2 103, pCO2 28, pH 7.17, HCO3- 10, AG 25, Lac 0.6) and laboratory tests showed creatinine 1.1 mg/dl, BUN 29 mg/dl, Sodium 140 mEq/L, Potassium 4.6 mEq/L, Chloride 104 mmol/L. No drugs, alcohols, lactate, ketones and salicylates were detected in her blood. Neurologic testing including computed tomography were unrevealing. Thus, the treatment with intravenous administration of 150 mEq sodium bicarbonate was started and acid–base imbalance was normalized with improvement of neurologic symptoms within few hours. The patient was transferred to our department of internal medicine to evaluate the etiology of metabolic acidosis and neurological symptoms. Thus, toxins, ketoacids, inorganic acids and lactic acidosis (D–L) were postulated as differential diagnosis. In view of by pass jejuno-ileal, D-lactic acidosis (DLA) was suspected and we proposed a carbohydrate load that patient refused. Three days later, after a meal, the patient showed the same neurological disturbances and physical weakness as presented on admission. During this acute episode, arterial blood gas analysis showed high anion gap normocloremic metabolic acidosis and sera and urine were collected to measure the level of D-lactic acid (colorimetric assay kit, EnzyChromTM D-Lactate Assay Kit, BioAssay Systems, Hayward, CA, USA).The levels of serum and urinary D-lactic acid were high at 27.2 and 32.4 mmol/L, respectively (normal range 0–3 mmol/L). Treatment was started with intravenous administration of sodium bicarbonate and over the next 12 h the patient gradually recovered from neurologic impairment and the acid–base imbalance was normalized. After this second episode we decided to reduce carbohydrate intake. However, 2 days later the patient presented the third episode of metabolic acidosis with confusion, slurred speech, anxiety, weakness appearing drunk. Sera and urine collected of D-lactic acid levels were high. Because of increased numbers of evacuations from three to seven daily, raise of temperature up to 38.5C and diffuse abdominal pain, stool cultures were performed showing positivity for Salmonella enteritidis sensible to ciprofloxacin. Therefore, the patient started ciprofloxacin 500 mg twice daily for a week. She also received

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Accurate clinical exam and doppler ultrasound rectified the wrong lecture of computed tomography images. Internist doctor’s mind better than any machine A. Savino1, A. Spinelli1, S. Contri1, A. Berni1, A. Peris2, M. Bonizzoli2, M. Boddi1

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 1

Dipartimento di Area Critica Medico-Chirurgica, Azienda Ospedaliero-Universitaria Careggi, Firenze; 2Anaesthesia and Intensive Care Unit of Emergency Department, Careggi Teaching Hospital, Florence, Italy A 32-year-old woman born in Philippine was admitted to the Emergency Department of our hospital after a defenestration. She had no history of hypertension. At Emergency Department a total body CT with the administration of contrast material was performed and documented multiple costal fractures, pleural and peritoneal effusion, with liver and spleen hematomas, but ruled out traumatic damage of thoracic and abdominal aorta. She was transferred to ICU of DEA (Dr A. Peris) for a strict hemodynamic monitoring. The right radial artery was cannulated after an abortive attempt made on both femoral arteries. Twelve hours after admission at the Emergency Department both femoral, popliteal and pedidial pulses were hardly detectable at palpation. A Doppler ultrasound evaluation of the abdominal aorta, iliac arteries and arteries of lower limbs was asked to rule out the sub-acute onset of traumatic dissection: the exam revealed a post-stenotic blood flow pattern along abdominal aorta, iliac arteries and inferior limb arteries that was not secondary to focal stenosis or dissection of examined vessels. No signs of atherosclerotic damage was detectable along the vessel wall of aorto-iliac and inferior limb arteries. Along carotid arteries, subclavian and upper limb arteries a triphasic blood flow pattern was instead assayed. Ankle-brachial index was 0.6. Because of the young age of the patient, the absence of risk factors and signs of atherosclerosis, no clinical or laboratory signs suggestive for arteritis, the diagnosis of aortic coarctation was hypothesized and the radiologist was asked to again exam CT scan images that had been reported to rule out pathologic features of thoracic and abdominal aorta. As expected a isthmic aortic coarctation was detected with a residual intralumen diameter of 3.2 mm. The first examination of CT scan at Emergency was aimed at detecting traumatic damage and aortic caliper was not examined in detail. At discharge from ICU, the patient refused to be further evaluated for surgical correction of aortic coarctation. The accurate clinical evaluation of the patient supported by Doppler ultrasound data allowed to underscore a bad mistake of a second level diagnostic tool that could have had relevant consequences for the right clinical follow-up of the patient.

In the heart of myeloma R. Scipioni, M. Struglia, G. Di Lauro, L. Natali, M. Ruggieri, V. Festuccia, C. Ferri Division and School of Internal Medicine, University of L’Aquila, San Salvatore Hospital, L’Aquila, Italy A 51 year-old women was admitted to our Department of Internal Medicine due to a 6-month history of progressive dyspnea, palpitation and lower extremity edema. The patient reported a surgical intervention due to a carpal tunnel syndrome, 2 years ago, and frequent episodes of diarrhea in the last 6–7 months. On physical examination she had blood pressure 100/70 mmHg, heart rate 110 beats/min, basal reduction of vesicular murmur and lower limbs edema. Laboratory exams were remarkable for increased levels of circulating LDH, BNP and uricemia. Protein electrophoresis revealed low total protein and hypo-gammaglobulinemia, urinalysis showed proteinuria. Thoracic X-ray showed modest pleural effusion. 12-lead ECG revealed sinus tachycardia with low-voltage QRS. Transthoracic echocardiography demonstrated asymmetric hypertrophy of the left ventricle with diastolic dysfunction. In the hypothesis of cardiac amyloidosis (CA), we

S235 performed a cardiac magnetic resonance that showed global subendocardial late gadolinium enhancement. Rectal and abdominal biopsies were negative while the endomyocardial biopsy confirmed the diagnosis of CA. Accordingly, in addition to proteinuria and hypogammaglobulinemia we also demonstrated positive serum immunofixation for clonal k free light chains. Bone marrow biopsy demonstrated 50% monoclonal plasma cells. Thus, the final diagnosis was of light-chain amyloidosis (AL) with cardiac involvement. Appropriate treatment was immediately started at entry, but patient died of acute left ventricular failure. Amyloidosis includes different diseases that share in common the extracellular deposition of insoluble fibrillar proteins in organs and tissues; the amyloidosis AL is caused by deposition of amyloid fibrils, the precursor of which is the N-terminal portion of immunoglobulin light chain. This abnormal protein (M-protein) is produced by plasma cells whit a monoclonal proliferative process. Amyloidosis AL affects more men than woman (3:2), usually around the sixth decade of life and involves the heart in 60% of the cases. Amyloid deposition in the heart results in rapidly progressive heart failure because of restrictive cardiomyopathy. The echocardiographic findings of amyloid infiltration of the heart consist of thickened right and left ventricular walls, ‘‘granular’’ appearance of the myocardium, normal or small left ventricular size, atrial enlargement and depressed left ventricular systolic and diastolic function. Low-voltage QRS (defined as all limb leads \5 mm in height) and pseudoinfarction pattern are also common at the ECG. Recent descriptions of cardiac magnetic resonance in advanced cardiac amyloidosis show global sub-endocardial late gadolinium enhancement and associated abnormal myocardial and blood-pool gadolinium kinetics. The diagnosis of amyloidosis requires a tissue biopsy that demonstrates apple-green birefringence when stained with Congo red and viewed under a polarizing microscope. The endomyocardial biopsy sample ensure near 100% sensitivity for detecting disease. Extra-cardiac manifestation are nephrotic syndrome, hepatomegaly, carpal tunnel syndrome and peripheral/autonomic neuropathy (frequently characterized by hypotension and diarrhea). Carpal tunnel syndrome often precedes other organ involvement by a few years, and a history of surgical carpal tunnel release is not uncommon. Management of cardiac amyloidosis requires the management of cardiac-related symptoms and treatment of the underlying disease. Unfortunately, the advanced nature of the cardiac disease at the time of diagnosis, as it was in our patient, either makes the patient unfitting for high-dose chemotherapy with autologous stem cell replacement or places the patient at risk of peritreatment mortality. Early diagnosis is critical for improving the response to therapy and increase survival. Thus although CA is a rare condition, it must be always suspected in patients manifesting with an history similar to that of our patient.

A rare case of biventricular hypertrophy L. Semprini, M.B. Musumeci, F.M. Cauti, A. Serdoz, V. Mastromarino, M. Volpe, C. Autore Universita` di Roma Sapienza, Facolta` di Medicina e Psicologia, Cattedra di Cardiologia, Azienda Ospedaliera Sant’Andrea, Roma, Italy Thirty-five years old man was referred to our outpatient clinic for recurrent palpitations. At first evaluation ECG showed sinus rhythm, narrow Q waves in inferior leads, T waves inversion in lead V1–V3, signs of biventricular hypertrophy (Fig. 1). Physical examination revealed short stature, exophthalmos, hypertelorism, pectus excavatum, low-set ears, and multiple dental abnormalities. The patient referred only a previous history of syncope, considered neurally mediated in origin.

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He was thus evaluated with an echocardiogram that showed good systolic function, biventricular hypertrophy (maximal wall thickness 18 mm); diastolic dysfunction; redundant and thickened mitral valve with incomplete systolic anterior motion (SAM) and mild regurgitation. He was eventually diagnosed with HCM. During follow up a cardiopulmonary exercise test demonstrated slight abnormal peak oxygen uptake (19 ml/kg/min), physiologic blood pressure response and no exercise induced ECG repolarization abnormalities; electrocardiographic Holter monitoring showed a single short episode of NSVT. Even if a diagnosis of HCM was made, it was necessary to differentiate a typical sarcomeric HCM and a rare form of syndromic HCM. Based on the clinical clues, suggesting a possible Noonan Syndrome (NS), the patient was screened for PTPN11 genes. No abnormalities in PTPN 11 was found. He was eventually evaluated with a cardiac magnetic resonance (CMR) that confirmed the presence of a biventricular hypertrophy (in the absence of ventricular obstruction or valvular stenosis) with mild late gadolinium enhancement. The patient was followed for 4 years and his clinical conditions remained stable. A further gene screening which included new candidates genes was performed and finally demonstrated a pathogenic mutation in RAF-1 gene. Even though NS is a rare disease with an estimated incidence between 1:1,000 and 1:2,500 live births this case highlights the importance to considering this diagnosis for unexplained biventricular hypertrophy in the presence of clinical typical clues, even in adult patients. This case also highlights the importance of familiarity with the characteristic features of NS for clinical geneticists, cardiologists, surgeons, anaesthetists, gynaecologists, paediatricians and dermatologists and the importance of genomic screening.

and cooked fish for dinner. In his medical history there were benign prostatic hyperplasia, surgical excision of bladder papillary urothelial low grade carcinoma, extracorporeal lithotripsy for ureteral lithiasis. At the physical examination only a mild liver enlargement was noticed; there was a little decrease in SpO2 (94% in room air) with no signs of dyspnoea. Laboratory tests showed mild normocytic anemia, an evident increase of inflammatory markers (CRP 85 mg/dl; ESR 114 ml; serum fibrinogen 687 mg/dl), cholestatic hepatitis with AST/ALT ratio inversion. There was also increase of ferritin and both IgA and IgE. Given the available data, the diagnostic hypotheses were multiple (hepatotrophic viral hepatitis or other viruses hepatitis, bacterial gastroenteritis, parasites, diverticulitis, cholecystitis, cholelithiasis, vasculitis and other autoimmune diseases). However, the presence of desaturation made unlikely the possibility of food poisoning or other inflammatory diseases of the gastrointestinal tract. The most likely diagnostic hypotheses were those of CMV infection and vasculitis. All serologic tests for hepatitis viruses (HAV, HBV, HCV, HEV, EBV and CMV) were negative. All the cultural microbiological tests (blood, urine and stool) were negative. Two iodine stool microscopic examination carried out in different days turned out to be negatives for parasitic larvae or eggs. The search for autoantibodies (ANA, ANCA, AMA, ASMA, LKM) was then performed. Chest X-ray did not show any parenchymal involvement. An abdominal ultrasonography did show mild enlargement of the liver without any ultrasonographic abnormality. The biliary tree was normal. A week after the admission the blood count showed eosinophilic leukocytosis (6.7 9 109/L). With these new data available, it seemed even more likely the possibility of vasculitis. However we could not rule out parasites. The assumptions of hypereosinophilic syndromes, Loeffler’s syndrome, haematological malignancies and invasive aspergillosis were less likely due to poor pulmonary involvement. At that point other diagnostic tests were performed: serologic tests for Ameba, Schistosoma, Echinococco, Giardia and Toxocara. A chest CT scan was performed to get a better understanding of pulmonary involvement. The scan showed bilateral interstitial ‘‘ground glass’’ infiltrates. Meanwhile the search for autoantibodies showed a non-specific pattern and a nonsignificant antibody titer making the diagnostic workup even more confusing. Eventually serologic tests showed the presence of the antitoxocara antibodies. Those, the diagnosis of toxocariasis (visceral larva migrans, VLM) was made on the bases of positive serological results, cholestatic hepatitis and eosinophilic leukocytosis. Ophthalmoscopic examination of fundus (performed due to the frequent presence of the larva in the eye) revealed no injuries. Due to the severe involvement of liver and lung treatment with albendazole (400 mg twice/day for 5 days) in combination with corticosteroid (prednisone 25 mg once/day) was started as described in literature. Few days after initiation of therapy we observed the appearance of an urticarial rash that resolved with the integration of antihistamine therapy. The patient was seen as an outpatients 3 weeks later: the blood tests showed complete normalization of blood count, IgE and liver enzymes, as expected target of the treatment.

An unusual case of fever, cholestatic hepatitis and eosinophily

Bone pain in an hepato-renal-transplanted patient

V. Sicbaldi1, R. Ghio1, E. Arboscello1, V. Del Bono2, E. Molinari1, L. Del Corso1, D. Lovera1, A. Bellodi1

M. Soattin, N. Vitturi, S. Giannini, M. Preto, C. Cattelan, G. Realdi

1

Clinica di Medicina Interna 3, AO San Martino e Cliniche Universitarie Convenzionate; 2Clinica di Malattie Infettive, AO San Martino e Cliniche Universitarie Convenzionate, Genova, Italy A 66-year-old immunocompetent man was admitted to our Dept because of fever lasting from about a week associated with nausea and vomiting that did not respond of antibiotic therapy with levofloxacina. The patient was a florist. He made a trip to Libya few months earlier and the night before the onset of symptoms he had mushrooms

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Clinica Medica 1, Dip. Scienze Mediche e Chirurgiche-Azienda Ospedaliera di Padova, Padova, Italy GP, male 62 years, comes for the appearance, 15 months before, of severe worsening pain, localized to the tarsal regions of both feet and ankles, knees, pelvis, lumbar and thoracic column, aggravated by load and mobilization (including simple pronation and supination of the feet) and relieved by bed rest. These symptoms were associated with joint stiffness and had led to a extremely difficult walking. His medical history reported arterial hypertension with hypertensive heart

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 disease, bile reflux, HP-gastritis; 10 years before, detection of HCVrelated cirrhosis with cryoglobulinemia; 2 years before, hepatorenal syndrome with progression to end stage renal failure requiring hemodialysis, followed by combined liver and kidney transplantation; monoclonal gammopathy. Pain appeared about 4 months after transplantation. Two months after an NMR of the ankles and feet showed ‘‘hypointense signal on the talar dome in T1 and T2 hyperintensity as edema of the trabecular spongiosa’’; a subsequent physiatric consult did not lead to any therapeutic measure; 2 months after was diagnosed a ‘‘sensory-motor neuropathy caused by HCV and immunosuppressive neurotoxicity’’. It was therefore amended the immunosuppressive therapy, replacing the tacrolimus with rapamycin, but this does not lead to an improvement of symptoms. The patient was then sent to the hospital for rehabilitation and he came to a internal medicine evaluation. The physical examination showed a good general condition. There were hypotonia and diffuse muscle atrophy, more marked in the legs, with concomitant purple lesions and edema; pain was summoned by pressure of the ankles and tarsal regions, less pronounced against the knees, pelvis, spine and chest, and worsened by mechanical load and mobilization. From the neurological point of view, muscle strength was normal at the legs while tactile sensitivity was reduced. Blood tests showed normal blood count and liver function, mild renal impairment (serum creatinine 1.51 mg/dl, BUN 48.6 mg/dl) with normal ionemia. Markers of inflammation were elevated (ESR 46 mm/ h, CRP 7.22 mg/l), a slight monoclonal component of 2.74 g/l (IgM with K type light chain) was evident with positive BJ proteinuria; Cryocrit 4%; Rheumatoid Factor 1,160 kU/L, normal C3 and C4, HCV RNA 9,297,479 IU/ml, genotype 2a–2c; Serum calcium 9.4 mg/ dl, phosphorus 1.24 mg/dl, vitamin B12 1,035 ng/l, folate 9.5 nmg/l. The main problems were: (1) widespread pain in the appendicular and axial skeleton in a patient with hepato-kidney transplantation for HCV-related cirrhosis, cryoglobulinemia and associated with a recentonset MGUS, (2) joint stiffness; (3) Deambulation increasingly difficult. The two main diagnostic hypotheses were neuropathic pain and bone pain. Neuropathic pain, however, was excluded because there was no significant depletion in vitamins, there was a significant cryoglobulinemia and bone pain did not appear as a compatible manifestation; jatrogenic origin by immunosuppressants had been denied by the lack of response to the replacement of the immunosuppressive drug. Among the diseases potentially responsible for such widespread bone pain, the hypothesis of multiple myeloma was considered, given the presence of monoclonal component and positive BJ proteinuria. However the subsequent bone biopsy and myelogram were not compatible. Among the metabolic bone diseases, we considered the osteosclerotic ones (pain from bone expansion/ compression and periosteal tissue compression) and osteolytic (pain from fractures or diffuse osteomalacia). The patient had already carried out several investigations, including biochemical phosphocalcium metabolism profile, X-rays of skull, spine, pelvis, hips, knees and ankles; NMR of the pelvis, knees and ankles, a total-body bone scan. Biochemical investigations showed normal serum calcium (9.40 mg/dl), hypophosphatemia f (1.24 mg/dl), low 24 h-urine calcium (95.2 mg) and phosphate (337.9 mg) excretion, normal serum PTH and 25(OH)D3; increased total (240 l/l) and bone-specific (70.8 lg/l) alkaline phosphatase), reduced tubular transport of phosphate (TmPi 1.7 mg/min). X-ray pictures showed a small osteolytic area in the right parietal bone, multiple vertebral fractures; NMR: T1 weighted scan: hypointense signal in the right femoral head and neck, hypointense signal in the talar dome and the anterior calcaneus; T2 weighted scan: hyperintense signal in the right femoral head and neck, hyperintense signal in the talar dome and the anterior portion of the calcaneus. The bone scan showed many areas of abnormal tracer hyperfixation to feet, knees, hips, spine-lumbar vertebrae, ribs. These data suggested that the most likely hypothesis was osteomalacia. Among the various forms of osteomalacia, the patient had the hypophosphatemic one, induced by a renal tubular loss of phosphate, which

S237 is characterized by: (1) from a clinical point of view, bone pain, proximal muscle weakness with difficulty rising from a chair, walking and climbing stairs, fractures, skeletal deformities, susceptibility to falls, bone-oedema syndrome, (2) from the biochemical point of view, low serum phosphate and reduced tubular transport of phosphate, normal or low 24 h-urine calcium excretion, increased bone-specific alkaline phosphatase The patient was placed on therapy with oral phosphate (750 mg 9 4/die), calcium 0.5 g/day, calcitriol 0.5 lg/day, obtaining a regression of the osteoarticular pain and resumed walking.

An abdominal pain in disguise M. Tagliente, N. Vitturi, F. Simoni, G. Realdi Clinica Medica I, Policlinico Universitario, Padova, Italy A 88 year-old woman was admitted to our department for the occurrence of repeated pre-syncope episodes in the days preceding admission, which were symptomatic for dizziness and light-headedness. In the same period she reported worsening weakness and repeated episodes of chest pain with dyspnoea. On admission patient was alert and oriented. Blood pressure was 190/85, heart rate was 56 bpm, SpO2 was 99% while breathing room air. Physical examination was normal except for a heart murmur 3/6 present on all the examined areas, radiating to the neck. The abdomen was diffusely painful to deep palpation, especially in lower quadrants. The medical history included poorly controlled hypertension, threevessel critical coronary artery disease previously treated with two consecutive percutaneous coronary angioplasties and dual antiplatelet therapy (aspirin and clopidogrel), severe aortic stenosis, previous right mastectomy for breast cancer and previous right colectomy for adenocarcinoma of the colon. On the second day after admission the patient complained of acute abdominal pain: abdomen was diffusely tender with markedly positive Blumberg sign especially in the lower left quadrant, bowel sounds were diminished but present, at deep palpation no masses were found, there weren’t fever, nausea, vomiting or melena. Laboratory investigations showed decreased haemoglobin (85 g/L) with normal platelet count, prothrombin time and activated partial thromboplastin time. A direct abdomen X-ray showed a picture compatible with intestinal subocclusion; an ultrasound of the abdomen was negative for peritoneal free fluid but showed a patchy mass compressing the right lateral wall of the urinary bladder. Subsequently, a thoracic-abdominal CT excluded the presence of intra-abdominal free air, but described a non-enhanceable pelvic hematoma of 8 9 5 9 6 cm in the right internal obturator muscle, which was the likely cause of both the symptomatic anaemia and acute abdominal pain. The patient had no history of trauma during the weeks before hospitalization, denied any dysuria or gross hematuria has well as any changes in her dietary or bowel habits. The hematoma was therefore likely spontaneous and due to dual antiplatelet therapy. Patient was treated with intravenous fluids and received 2 units of packed red blood cells. Aspirin therapy was withheld thereafter. Haemoglobin levels gradually normalized, the hematoma had been spontaneously reabsorbed in 9 weeks with regression of the abdominal pain. The present case shows a rare dual antiplatelet therapy side-effect, hematoma of the obturator muscle, which is an atypical localization of bleeding, and manifested as an acute abdominal condition mimicking an acute abdomen. After review of the literature we found no data about the incidence of hematomas in atypical localizations. In general, yearly risk of major bleeding is 2.6% with aspirin, 3.7% with dual antiplatelet therapy and 12% in dual antiplatelet therapy plus warfarin. Atypical localizations of spontaneous abdominal hematoma during dual antiplatelet therapy have rarely been reported, mainly in the ileopsoas and rectus abdominis muscles; most of the reports of

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S238 spontaneous hematoma, indeed, are related to warfarin or heparin therapy. Occurrence of spontaneous hematoma in the internal obturator muscle, due to dual antiplatelet therapy, had not been reported to date. Also, hematomas of the rectus abdominis are known to mimic an acute abdomen but such occurrence had not previously been reported with those localised in the obturator muscle. We present the first case of spontaneous hematoma of the internal obturator muscle, in a patient treated with aspirin and clopidogrel, which mimicked an acute abdomen, probably due to peritoneal irritation.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Disease) support our diagnosis, adding the anamnestic date of recurrent epistaxis. According to the 4 CuraC¸ao criteria: nor (1) cutaneous or mucosal telangiectasias were evident on physical examination, nor other (2) visceral lesions except PAVMs, nor (3) family history were present in our patient. Therefore PAVMs and the (4) recurrent epistaxis allow to consider possible the diagnosis (definite diagnosis if 3 criteria are present, possible if 2 criteria are present).

Drunk cells A case of dyspnea in a woman with muscular dystrophy

L. Trotta, P.I. Bianchi, L. Magnani, F. Biagi, G.R. Corazza

C. Tozzetti, C. Alamanni, A. Berni, M. Torri, L. Poggesi

First Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy

Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy We describe a case of a 46-year-old women affected by Steinert’s familiar myotonic dystrophy; she had been in her usual state of health before the age of forty, except for legs and hands myotonic phenomena. The patient had a history of recurrent episodes of epistaxis in childhood and hypothyroidism in substitutive treatment. Approximately 2 months before admission, a progressive dyspnea on exertion developed, leading the patient to decrease working activity. During a periodic pneumologic visit, expected in the global evaluation of muscular dystrophy, an arterial blood gas analysis reveals partial respiratory failure with respiratory alkalosis (pH 7.47, pO2 77.1 mmHg, pCO2 28.3 mmHg, HCO3 20.9 mmol/L, BE -1.5 mmol/L), confirmed in nocturnal polisonnography; she was discharged recommending to start nocturnal non invasive ventilation, BiPAP version. Muscular dystrophies, involving respiratory muscles, could lead to respiratory failure, most of them hypercapnic due to hypoventilation. The patient was admitted to this hospital because of worsening dyspnea. In the Emergency Department, the hypoxemic hypocapnic respiratory failure was confirmed (pH 7.51, pO2 60.9 mmHg, pCO2 24.9 mmHg, HCO3 23.0 mmol/L, BE -1 mmol/L); a chest X-ray study showed consolidation located in the lower right lobe. The Wells’ score was 0 and a D-dimer essay was 180 lg/L (cut off \ 250 lg/L). Seen in our ward, on physical examination vital sign were normal (temperature was 36.6C, blood pressure 100/70 mmHg, heart rate 90 beats/min, respirations 20 breaths/min); breaths sounds were present bilaterally, heart sounds of normal intensity; no jugular vein distension, no pedal edema and no hepatomegaly were evident. She was eupnoic at rest, asthenic for moderate exertion. The ECG showed a sinus rhythm and a two dimensional transthoracic echocardiography normal cardiac chambers. Hypoxemia was only partially corrected by increasing the inhaled FiO2, oxygen saturation not going further than 93–94% while the patient was breathing in FiO2 35%. The hypothesis of an active pneumonia was ruled out according to clinical and laboratory-test (absence of fever and leukocytosis in a young immunocompetent women). Our focus was on refractory hypoxemia that could support pulmonary embolism or right to left shunt both of cardiac or pulmonary origin. Chest CT scan, performed even to exclude pulmonary embolism or pulmonary origin of shunt, allows to detect multiple pulmonary arteriovenous malformations (PAVMs) located bilaterally, in the medium lobe, in the inferior left lobe (maximum diameter 2–3 cm) and smaller ones in the upper lobes. PAVMs were thought to be responsible of the severe acute respiratory failure, confirmed by the hyperoxia test showing a pulmonary right to left shunt of about 20–25%. The patients was successfully treated by trans-catheter embolization of the three-major PAVMs. Positive effects of vasoocclusion of PAVMs resulted in gradual improving of dyspnea and arterial blood gases (pH 7.50, pO2 89.7 mmHg, pCO2 28.0 mmHg, HCO3 24.5 mmol/L). Estimation that at least 80% of PAVMs occur in the context of Hereditary Hemorrhagic Teleangectasia (Rendu–Osler–Weber

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A 35-year-old female patient was admitted to our hospital with polyuria and polydipsia. Her daily fluid intake was 9 l. The daily diuresis was 16 l. Three years earlier she had been suffered from osteoblastic and condroblastic osteosarcoma treated by surgery and chemotherapy. Two years after that she developed metastatic cancer to the lower lobe of the right lung and underwent lobectomy. Three months before the admittance to our hospital she developed myelodysplastic syndrome (AREB-2). Cytogenetic analysis of marrow blastic cells demonstrated monosomy 7. She was treated with prednisone, red cell and platelet transfusion and she was waiting for bone marrow transplantation. She complained about fever (37.5–38C) and shivers in the last 2 weeks. She had no family history of diabetes mellitus. Physical examination was normal except for pallor, dryness in her skin and mucosa and the signs of surgical intervention on the right leg and on the thorax. On the admission in hospital, sodium and potassium levels were 144 and 3 mEq/L respectively, aldosterone 94 pg/mL (v.n. 35–300), ACTH 11 pg/mL (v.n. 5–50), creatinine 0.60 mg/dL. Urinalysis demonstrated a diluted urine with a low specific gravity (1,010). Urine did not contain glucose and there was no hyperglycemia. Serum osmolality was 286 mOsm/kg and urine osmolality was 60 mOsm/kg. Antidiuretic hormone (ADH) level was undetectable. White blood cell count was 4.24 9 109/L, with 91% lymphocytes. Hemoglobin level was 8.7 g/dL and platelet count was 467 9 109/L. She was found to have central diabetes insipidus, as demonstrated by a water deprivation test. Under water deprivation, blood osmolality rose to 305 mOsm/kg 2 h later, while urine osmolality rose to 354 mOsm/kg 3 h after desmopressine administration. A magnetic resonance imaging (MRI) scan of the brain showed only an aspecific delayed enhancement of the pituitary gland and there was no sign of a tumor. Oral desmopressin treatment, 60 lg t.i.d., was begun and polyuria and polydipsia promptly improved. During hospitalization, platelet count rose to 593.000 9 109/L, and acetylsalicylic acid 100 mg was started. The leukocyte count remained stable but with 95% lymphocytes and 77% blastic cells on peripheral blood smear. A leukemic evolution of the myelodysplasia was suspected. Haematologist performed a bone marrow examination that confirmed the diagnosis. A rachicentesis excluded the presence of micrometastases to the brain. The patient underwent the bone marrow transplant. After a month, the blood cell counts dropped to normal ranges, an MRI scan of the brain showed a totally normal pattern and desmopressin requirement dissolved. The gene encoding ADH resides on chromosome 7. Moreover, high platelet count may interfere with ADH level and function in the blood, because more than 90% of circulating ADH is bound to the platelets. In our patient, we observed that diabetes insipidus was improved when high platelet count dropped to normal ranges. The development of diabetes insipidus may be the first signal of acute myelogenous leukaemia with a high platelet count.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 About a boy L. Trotta, P.I. Bianchi, L. Magnani, E. Lovati, G.R. Corazza First Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy A 23-years-old boy admitted to our hospital had been suffering from chronic constipation, fatigue, abdominal pain, nausea, vomiting and occasional episodes of rectal bleeding for 2 months. He also reported anorexia and weight loss of 10 kg for the same period. He had no family history or past personal medical history of diseases. The physiologic history was normal. The cardiac, abdominal, thoracic, neurological examinations were normal. The body mass index (BMI) was 16 kg/m2; the arm, leg and shoulder muscle mass was reduced. The facial, pubic, axillary hair was sparse. The blood count showed normocytic anemia (Hb 10.9 g/dl, MCV 86 fl) with normal reticulocyte count. The biochemical tests showed high levels of indirect bilirubinemia (2.14 mg/dl). The LDH, aptoglobin, ferritin, erythrocyte sedimentation rate, C-reactive protein, vitamin B12, folic acid, neoplastic markers, ASCA, and ANCA were normal. The direct and indirect Coombs tests were negative. The anti-endomysial antibodies were negative. As a relative lymphocytosis was found, we performed IgG and IgM for EBV, and EBV DNA which were all positive. On suspicion of intestinal bowel disease, the patient underwent a colonoscopy with biopsies that was negative, except for internal haemorrhoids. In order to exclude an enteropathy, upper digestive endoscopy with gastric and duodenal biopsies was performed, showing normal macroscopic and microscopic features. Also chest-Xray and abdomen ultrasonography did not show any abnormalities. Moreover, thyroid activity was evaluated: T3 1.63 pg/ml (range 1.8–4.2), T4 5 pg/ml (range 8–19), TSH 0.4 mU/l (range 0.4–4). The anti- TSH, anti-thyroperoxidase and anti-tireoglobulin antibodies were all negative. So a central hypothyroidism was suspected. The laboratory tests showed normal FSH and LH, a reduction of testosterone levels 0.5 ng/ml (range 2.7–15) and a reduction of serum cortisol levels (4 lg/l, range 4.3–22), with normal ACTH and a normal response to the ACTH stimulation test. The prolactin levels were high (95 ng/ml, range 2.5–17); The GH was normal but IGF-1 was low (79.6 ng/ml, range 98–390). Finally, an MRI scan of the brain showed a large space-occupying intra and suprasellar lesion (1.8 9 1.8 9 2.2 cm) suspected for craniopharyngioma. The patient underwent trans-sphenoidal surgery. One month after the surgical intervention, the patient reported the resolution of abdominal symptoms, well-being and weight gain of 7 kg (BMI raised up to 20 kg/m2). The laboratory tests showed central hypercortisolism and central hypothyroidism with hypogonadotropic hypogonadism. The prolactin serum levels still remained high (43 ng/ml) because of a disruption of the hypothalamus-hypophysis axis. Patient started therapy with cortone acetate 25 mg/day, levo-thyroxine 50 lg/day and testosterone 250 mg/month. Three months after the surgery, a control MRI scan of the brain showed a relapse of the lesion, so the patient will undergo a second intervention next month. Despite a misleading clinical presentation, an in-depth clinical investigation may allow the correct diagnosis.

The importance of the Clinical investigation in making Diagnosis. High value of Ca 19-9 E. Verrecchia, A. Marinaro, C. Fonnesu, M. Giovinale, R. Manna Internal Medicine Department, Catholic University of Sacred Heart, Rome, Italy Nowadays, the medicine is based on plenty of technological tools and statistical data, in order to recognize and treat diseases faster and

S239 better. The frenetic research of a diagnosis, associated to the present economic situation, is leading to loose of view the principal focus of our mission: the patient. Indeed faster doesn’t mean always better, because it can lead to consider the disease alone, but not the patient. We described our experience with a patient that was searching for her diagnosis. Female, 65 y.o., history of cholecystectomy at age 40 for litiasis, started to complain fatigue in february. Since her symptoms did not ameliorate, her family doctor requested generic examinations, which showed anemia (hb 10.8 g/dl), and mild increased of AT (AST 45 U/l, ALT 37 U/l), hypercholesterolemia, and mild increased of oncomarkers (CA 15-3 45.2 U/ml, CA 19-9 92.31 U/ml, CEA 6.6 ng/ml), with normal value of creatinine, ferritin and folates; occult fecal blood was negative in 3 specimens. Based on statistical data that demonstrated an increased risk of colon tumors in persons older than 65 y.o., with irregularity of the alvus and anemia, in July the patient was admitted to Hospital to look for a malignancy. After routine analysis which confirmed normochromic and normocytic anemia with mild increased of CA 19-9, she underwent to a first endoscopy that had to be repeated in anesthesia for a strong intolerance to the examination. Both exams resulted negative and the patient was discharged with a diagnosis of dolicocolon, and nothing else. She still complained symptoms and needed further instruction on what she had to do. In order to have an advice on what to do, on August the patient asked help to an internist. This latter revaluated entirely the whole medical history of the patient and her examinations. So, in the anamnesis there was not familiarity of neoplasms, and the patient reported that the main symptom was the myalgia, associated with fatigue and constipation. In the routine blood examinations besides anemia and hypercholesterolemia (300 mg/dl), it was found also the elevation of CPK (1262 U.I.) and LDH (825 U.I). Acute fase reactants were negative (ERS 6 mm/h, C-reactive protein 0.7 mg/l), autoantibodies were negative (ANA, ENA, AMA). Thus, based on those data, an hypothesis of hypothyroidism was formulated. After a week, blood examinations revealed TSH 200.20 mU/L, fT3 1 pg/ml, fT4 0.1 ng/dl with anti TG 5,000 U.I./mL and anti TPO 994.20 UI/mL, thus to make diagnosis of Hashimoto’s thyroiditis. The patient started low doses of tiroxine, with progressive increase till the dosage of to 100 lg a day, with benefit, while CA 19-9 levels normalized. CA 19-9 must not be used to search tumors, since it can be increased in other conditions such as autoimmune hepatitis, cirrhosis, small cell lung carcinoma, litiasis of gallbladder, chronic renal failure, chronic pancreatitis, retroperitoneal cystadenoma, and in green tea drinkers; the same hypothyroidism can be associated with increased level of CA 19-9. In conclusion, If the anamnesis was focused on the patient instead of Ca19-9, the patient would avoid expensive exams.

Pulmonary opacities in a patient affected by mycosis fungoides M. Villiva`, L. Borgognoni, A. Russo, V. Fontana, P. Marinelli, V. Liparulo, M. Anile, S. Pascale, F. Vaccaro, A. Paris, P. Palange Sapienza Universita` di Roma, Policlinico Umberto I, Dipartimento di Sanita`Pubblica e Malattie Infettive, UOC Medicina Interna I, Roma, Italy A 55-years-old man was admitted to our ward because of the onset of asthenia, mild chest pain, low grade fever (37.6C) and blood leucocytosis 3 months before admission. He was treated with claritromicin three times but signs and symptoms were relapsing at the end of therapy. At that time lung CT showed the presence of multiple bilateral opacities in middle and inferior lobes and paratracheal, hilar, subcarinal, paracarinal and paraortic adenopathies with 5–30 mm diameter.

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S240 Case history revealed he smoked 1 pack/die for 35 years until 2 months ago. At the age of 23 he was diagnosed with mycosis fungoides and treated with mechlorethamine; at 28 he was treated with psoralen and PUVA; at the age of 42, 49 and 54 he was treated with Interferon-a 3,000\000 IU 3 days/week for 18 months; last course was completed 5 months before admission. He was also diagnosed with emphysema. About 4 months before admission he underwent excision of a balanic sulcus neoformation (histological exam described: ‘‘foreign body granulomatosis’’). Upon admission to our ward clinical examination showed presence of skin patches in various areas of thorax and abdomen and a papula in the right shoulder. We appreciated some ovoid, mobile and not painful centrimetric lymph nodes in neck and groin. Auscultation of thorax showed mild discontinuous sounds at both the pulmonary bases. Blood pressure was 120/60 mmHg, cardiac rate was 72 bpm, rhythmic. Laboratory tests confirmed leukocytosis and neutrophilia (11.770/ mmc; N 75%), ESR 68 mm/h, CRP 53.800 lg/l, electrolytes were normal and renal, hepatic, cholestatic and metabolic markers were normal too. ABG analysis evidenced hypoxemia (pO2 73 mmHg) and no acid–base homeostasis alteration. Spirometry showed a mild restrictive pattern (FEV1 pred. 70%; FVC 77%; FEV1/FVC 98%) and DLCO was 58%. During hospitalization we decided to execute a new lung TC exam which showed an increase of the opacities’ dimensions. Our suspicion was directed to infective, neoplastic and immunologically mediated pneumopathy. As first we performed the baseline microbiological tests: culture of the sputum was negative for common germs and fungi, Ziehl–Neelsen stain for AFB in sputum and urine was negative and TB gold was negative too. HIV (ELISA) test was negative; lymphocyte typing was normal with CD4/CD8 ratio 1.64. Serum ACE concentration was 24 IU/l. Therefore we decided to perform bronchoscopy with BAL. Bronchoscopy didn’t show any endobronchial tumour; culture of BAL was newly negative for common germs and fungi, the stain for AFB and P. jiroveci’s cysts were negative; Galactomannan ELISA assay was negative too. Lymphocyte typing of BAL showed CD4/CD8 ratio 2.44; None neoplastic cells were found in BAL. At this stage we could most likely exclude infective cause, so we decided to perform pulmonary biopsy of the lesions through thoracoscopy to clarify diagnosis; the histological exam showed: ‘‘not necrotizing epithelioid giant cell granulomatosis, consistent with pulmonary sarcoidosis and granulomatous lymphangitis’’. Because of the mildness of the clinical features, we decided not to start corticosteroid therapy and to observe the patient in the following months monitoring symptoms, DLCO, pO2 and 6MWT; however we believe that could be advisable to replace Interferon-a with another drug on the occasion of future mycosis fungoides reacutizations owing to the activating action of T lymphocytes and subsequent production of various cytokines which seems to be responsible of at least a part of sarcoidosis pathogenesis.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 persisting stable for about 1 year. He referred neither alcohol nor drugs abuse nor exposition to chemical agents. Abdominal examination showed an enlarged left liver lobe at light palpation. Hepatic ultrasonography (US) showed a massive sovversion of the liver parenchyma by multiple nodular lesions. Viral serology for the common hepatitis viruses, CMV, EBV, HSV, HIV, screening for autoimmunity and the main oncological markers were negative. FBC, kidney and synthetic liver function were normal. To exclude the presence of an extrahepatic malignancy, we performed a total body CT scan, showing a complex vascular malformation of the portal system (Fig. 1a), consisting in a portal-caval shunt determining a significant hypoperfusion of the right hepatic lobe and a hyperafflux to the right heart with the dilation of pulmonary arterial system, a voluminous lesion in the left lobe and multiple hypodense areas of uncertain significance in the residual parenchyma. Therefore, he underwent an abdominal RMI confirming the presence of an expansive lesion of the left lobe (13 cm) with necrotic areas on the inside, and the occupation by multiple hyperintense lesions up to 5 cm of the residual parenchyma, with contrastographic features compatible with hyperplastic alterations. It was evident a congenital-malformative portal-systemic shunt, with the absence of the intrahepatic branches of the portal vein and a compensative arterial hypertrophy supplied by the presence of an accessory branch of the hepatic artery (Fig. 1b). Cardiac US showed biatrial enlargement, mild tricuspidal insufficiency with signs of initial pulmonary hypertension and moderate mitral insufficiency. EGDS did not show signs of portal hypertension. Liver histology showed the typical histologic feature of nodular regenerative hyperplasia of the liver. No cell atypia was detected. Nodular regenerative hyperplasia (NRH) is a rare (0.72–2.6%) condition characterized by the growth of non-neoplastic regenerative nodules within the liver. Even if several predisposing conditions and systemic diseases have been recognized to be associated to NRH, its pathophysiology seems to be related to phenomena of functional vascular alterations through ‘‘atrophy–hypertrophy’’ mechanisms. Based on the available data the patient was diagnosed with NRH in type 1b Abernethy Malformation (congenital extrahepatic portosystemic shunt characterized by agenesia of the intrahepatic portal vein and complete end-to-side portal-caval shunt), and has begun the screening for liver transplantation.

Asymptomatic elevation of liver enzymes in a 26-year-old man D. Viviani1, F.R. Ponziani1, N. De Matthaeis1, G. Andrisani1, D. Galasso1, L. Guidi1, A. Armuzzi1, A. Papa1, I. De Vitis1, A. Gasbarrini1, A.M. De Gaetano2, F. Danza2, F.M. Vecchio3, G.L. Rapaccini1 1

Dipartimento Di Medicina Interna e Scienze Mediche Specialistiche; Dipartimento di Bioimmagini e Scienze Radiologiche; 3Istituto di Anatomia Patologica, Universita` Cattolica del Sacro Cuore, Roma, Italy

2

A 26-year-old man was admitted to our Gastroenterology Unit for a mild alteration of liver enzymes and signs of cholestasis with a severe increase in GGT levels (more than 8 times the ULN),

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Fig. 1 a CT scan: portal-caval shunt; b MRI: arterial hypertrophy of the liver; c, d MRI: nodular lesions of the right and left liver lobe, respectively.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Fever, skin eruption and bone lesions in an otherwise healthy 41-year-old man D. Viviani, M. Giovinale, A. Marinaro, R. Manna, R. Pola, R. Landolfi Dipartimento di Medicina Interna e Scienze Mediche Specialistiche, Universita` Cattolica del Sacro Cuore, Roma, Italy A 41-year-old Caucasian man, with no previous history or relevant diseases, was admitted to our Division of Internal Medicine because of fever, periodic bone pain, and the presence of erythematous skin lesions. Symptoms had started 5 months earlier, with skin lesions that were initially limited to the right thigh and had later extended to both legs and arms, the trunk, the chest and the neck. The skin lesions had maculo-papular appearance, a salmon-pink colour, and were painful. Fever (up to 39C) had also appeared a few months before and had a periodic occurrence, sometimes concomitant to the eruption of the skin lesions. Finally, in the last 5 months, the patient had been suffering from bone pain, at the level of the spine, the pelvis, the knees, and the right arm. Because of these symptoms, the patient’s general practitioner had suggested a whole-body CT scan, that was performed 2 months before the admission to our unit and showed the presence of a sclerotic bone lesion in the lumbar spine. This lesion was later confirmed by MRI. Our initial hypotheses included osteomyelitis and primary or secondary bone tumor. Blood tests found no increase in white blood cells, but showed increased levels of ESR (38 mm in the first hour) and CRP (24.2 mg/L). Liver and kidney function tests appeared normal. Also coagulation parameters were normal. Blood cultures were negative for pyogenic organisms, mycobacteria and fungi. Serologic tests were normal. Urine and stool cultures were negative. The heart ultrasound was normal. The blood levels of the principal oncomarkers were normal. The possibility that the patient was affected by a metastatic tumor was also excluded on the basis of the whole-body CT scan that he had already performed and had shown no evidence of other abnormalities except for the above-mentioned lesion of the spine. We also performed analyses to rule out the presence of an autoimmune disease, but the immunological tests that we carried out were negative. In order to better define the nature of the skin lesions, we performed a skin biopsy. The histological examination demonstrated a diffuse infiltrate consisting predominantly of mature neutrophils located in the upper dermis, consistent with Sweet’s syndrome. The patient underwent MRI of the pelvis and the spine, that showed multiple sclerotic bone lesions at the level of T1, T8, T10, T12, L3, and L4. A whole body bone scintigraphy was performed and showed significant pathological activity in L4, with additional multiple small areas of pathological uptake in the right omeral diaphysis, the left intertrochanteric region, and the right femural diaphysis. To understand the nature of these lesions, the patient underwent vertebral biopsy of L4. The histological examination did not detect the presence of tumor cells, but instead identified inflammatory cells with intense sclerosis and calcification. The bone biopsy was also used for microbiological studies and was found to be sterile, thus excluding infective osteomyelitis. Based on the available data, a diagnosis of Chronic Recurrent Multifocal Osteomyelitis (CRMO) was performed. Although CRMO is usually a disease of the childhood, several cases have been described in adults between 18 and 60 years of age. The concomitant presence of Sweet’s Syndrome is consistent with previous reports in the literature that have identified the association between neutrophilic dermatoses and the multifocal, aseptic bone lesions that characterize CRMO. No standard therapy exists for this clinical entity. No prospective studies are available, but only case reports and short series of patients.

S241 However, it is generally accepted that NSAIDs are beneficial and should be considered fist-line treatment. Steroids and sulfasalazine are considered in patients with frequent relapses or if NSAIDs must be discontinued because of ineffectiveness or adverse effects. Other therapeutic agents that have been used are methotrexate, TNF-alpha blockers, immunoglobulins, interferons, and colchicine. We treated our patient with etoricoxib (90 mg/day) and obtained remission of the skin lesions, as well as the fever and the bone pain. After 3 months of therapy the patient had a moderate relapse of the skin lesions, that responded to the addition of colchicine treatment. The patient is currently enrolled in a follow-up program at our Department of Medicine.

Hematology B-cell non Hodgkin lymphoma presenting with cryoagglutinins disease. A case report M.R. Barbella, F. De Stefano, R. Nappo, C. Palermo Rossetti, G. Gallotta Dipartimento di Medicina Clinica e Sperimentale, Universita` degli Studi di Napoli ‘‘Federico II’’, Napoli, Italy V.C., 59 years old, with history of coronary artery disease, seminoma at the right testis treated with surgery and radiotherapy which caused a slight impairment of renal function. He had arterial hypertension, and was a smoker. He presented to our Structure with anaemia and jaundice, severe dyspnoea, fatigue and dizziness. At admission, laboratory tests showed: RBC 2.97 9 106/mcL, Hb 8.9 g/dL, Hct 27%, blood iron 126 lg/dL, uric acid 7.8 mg/dL, indirect bilirubin 2.00 mg/dL, creatinine 1,4 mg/dL, beta2-microglobulin 3,824 ng/mL, ferritine 762 ng/dL, fibrinogenemia 561 mg/dL, C reactive protein 9,1 mg/dL. Thus, our patient presented an acute anaemia, which could have been caused by: renal failure, chronic inflammatory disease and hemolysis. The test tube had to be warmed during transport to laboratory because the patient’s blood tended to form clots very quickly. Even laboratorists noticed blood cells’ cryoagglutination. This evidence led us to the suspicion of an hemolytic anaemia brought by cold agglutinins. A direct Coombs test resulted positive for cold agglutinins and c3d. We, indeed, moved to search a possible etiology: screening for rheumatic diseases was negative, so did the test for Mycoplasma pneumoniae antibodies, and we performed a total body CT-scan to exclude solid neoplasias. After the injection of contrast medium, the patient experienced palpitations followed by chest pain. When he came back to our ward, EKG showed no ischemic modification, but a blood sample revealed Hb at 8 g/dL and raise in CK-MB, indicating an acute coronary syndrome (UA/N-STEMI): this condition was due to coronary atherosclerosis associated with low oxygen deliver by blood cells. It was necessary performing a blood transfusion, in order to mitigate myocardium oxygen demand. Few days after, the patient noticed a slight raise in the body temperature (37.7C), associated with the appearance of a swollen lymh node in the right axilla. The node had 1 cm transverse diameter, and wasn’t painful. We executed, then, an agobiopsy, and the cytological examination resulted positive for malignant cells, CD-20+, and the diagnosis was diffuse large B cell non Hodgkin lymphoma. After the diagnosis and before treatment, it was necessary the disease staging. For this purpose, the patient underwent a PET scan: high uptake was found in nodal groups above and below the diaphragm: the disease was in stage III. The therapy regimen was R-CEOP: this included the monoclonal antibody rituximab, active against the CD-20, which, in clinical experimentations, showed improvement of the 5 years survival.

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S242 Delayed diagnosis of systemic al amyloidosis with pulmonary involvement S. Caravita1, S.C. Wu1, V. Dadone2, A. Maggioni1, M. Gariboldi3, Mb. Secchi1 U.O.C Medicina Interna; 2U.O.C. Cardiologia; 3U.O.C. Radiologia, Ospedale Bassini, Istituti Clinici di Perfezionamento, Milano, Italy

1

Introduction: Amyloidosis refers to a variety of disease entities that are characterized by abnormal extracellular deposition and accumulation of amyloid proteins. As it is well known, the classification of amyloidosis depends on the different structure of the variable fibrillar protein constituent. The majority of amyloidosis are of the primary or secondary type. In primary amyloidosis, the characteristic fibrillar protein is a fragment of the variable immunoglobulin light chain so that it is defined as amyloid light chain (AL) amyloidosis. The disease becomes clinically significant when its diffuse form affects organs function by disrupting architecture (kidney, heart, liver, gastrointestinal tract, respiratory tract, urinary tract, peripheral nervous system, autonomic nervous system, soft tissues) or by the mass effect of its more rare focal form. Numerous symptoms are associated with this disease, but too often AL amyloidosis is misdiagnosed or its diagnosis is delayed, considering that nowadays there are better and more encouraging therapies. The Authors describe a case of overt AL amyloidosis that could have been diagnosed even a few years before because of signs and symptoms suggestive of amyloid multiorgan involvement, although with atypical lung presentation. Case report: A 67-years old man came to our attention because of clinical picture of overt congestive heart failure in October 2010. He had previously underwent surgery for nasal basocellular carcinoma and nasal polyps and in 2007 he had underwent surgery for bilateral carpal tunnel syndrome. During the same year dysphonia, dysgeusia, submandibular swelling and initial macroglossia appeared. A ENT consultation resulted negative. In June 2008 an abdominal CT performed for persistent microhematuria showed, at the thoracoabdominal transition, pulmonary consolidation posteriorly at both lung basis, interpreted as dystelectasis. In the same period, along with the aforementioned signs and symptoms, fatigue, exertional dyspnea, facial purpura and shoulder pads appeared, with recurrence of hand paresthesias and dysesthesias. The whole clinical picture have worsened until the patient came to our attention, when peripheral edema and dyspnea at rest and voiding obstructive symptoms were present. After prompt diagnosis and dilatation of urethral stenosis, with the usual therapy of congestive heart failure, the patient significantly improved. A thoracentesis was performed showing transudate. The ECG showed low voltage of atrial and ventricular complexes in the peripheral leads. The echocardiogram demonstrated thickening of interventricular septum and postero-lateral papillary muscles with granular sparkling appearance of the myocardium, signs of increased left ventricular filling pressures (E/E0 [ 15) and moderate biatrial dilatation. Serum protein electrophoresis was unremarkable, but urinary kappa and lambda light chains were 399 and 5 mg/L respectively (normal values 0–10). Periumbilical fat biopsy was performed with demonstration of congophilic fibrillar deposits birefringent under polarized light. A plasma cell infiltrate (20–25%) with clonal restriction for kappa light chains was present at bone marrow biopsy. Chest and abdominal CT revealed two subpleural nodular parenchymal consolidation at the middle right pulmonary lobe and parenchymal consolidation at the basal segment of the inferior pulmonary lobes; moreover there was significant imbibition of chest wall, mediastinic, paracardiac, mesenteric and omental adipose tissue. The patient at this moment has completed six courses of a therapeutic schedule consisting of melphalan 16 mg and dexamethasone 20 mg from day 1 to day 4 every 28 days with a reduction of free serum kappa light chains of 65% (2,200 ? 989 mg/L). The chest CT

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 showed discrete reduction of subpleural consolidations. A new treatment schedule including lenalidomide is being started. Conclusions: (1) In our opinion this case came to a delayed diagnosis even if characteristic signs and symptoms of amyloidosis were present for a long time with a very impressive involvement of many organs and tissues. (2) It deserves attention that pulmonary involvement of amyloidosis is more typically of peripheral and subpleural nodular-type, but it can also occur as diffuse alveolar septal involvement (our case presents both forms). It’s important to remember that although the alveolar form has been reported just in few cases, in autopsy series diffuse parenchymal amyloid deposition is a common histologic finding in systemic amyloidosis.

Two cases of amyloidosis: determinant role of abdominal ultrasound in the diagnostic pathway G. Carnevale Maffe`1, L. Brunetti1, E. Oriani2, M. Gnocchi3, R. Ciccocioppo1, G.R. Corazza1 1

First Department of Medicine, Fondazione IRCCS Policlinico S. Matteo, University of Pavia; 2Department of Internal Medicine, Ospedale Civile SS Antonio e Margherita, Tortona; 3Department of Internal Medicine, Ospedale Civile, Voghera, Italy Patient A, a 74 year-old men, was admitted to our department because of dyspnea and peripheral edema. His previous history included vascular disease (acute myocardial infarction 14 years before), chronic renal failure and benign prostatic hyperplasia. Two years earlier he presented peripheral edema, asthenia and dyspnea due to massive pleural effusion which required multiple thoracocentesis. On admission to our department a chest-abdominal CT showed a significant abdominal lymphadenomegaly suspected for a lymphoproliferative disorder and the presence of an hypodens tissue largely localized around the kidneys. Abdominal ultrasound showed a hyperechoic mass widespread around pancreas, hepatic hilus, mesenteric vessels and kidneys, including some calcific lymph nodes. Moreover, it was evident a hyperechoic structure of kidneys and a markedly hyperechogenicity and thickening of the retroperitoneal tissue in perirenal and peribladder spaces. We also found an increased thickness of gut wall, more evident at the distal part of left colon. These findings suggested for an accumulation disorder. Patient B, a 50 year-old men, came to our attention complaining of stomach ache and weight loss of about 20 kg. Abdominal ultrasound revealed marked hepatomegaly, with round borders and a evident reduction in echo penetration, increased volume and echogenicity of kidneys, micronodular pattern of the spleen and gut involvement with severe small bowel dilatation, increased wall thickness and mesenteric hypertrophy. Even in this case these ultrasonographic findings suggested for an accumulation disorders. Our particular expertise in the echographic aspects of amyloidosis led us to suspect this condition in both cases. This diagnosis was subsequently confirmed in both patients through the histological demonstration of amyloid fibrils in abdominal fat and through the valuation of haematological parameters traditionally considered for this disorder. In particular, patient A was diagnosed for AL amyloidosis with IgMk monoclonal component in the serum and Bence Jones k proteinuria, while patient B was diagnosed for AL amyloidosis with monoclonal component in serum and urine. Conclusions: We think that these two cases are of particular interest because the use of abdominal ultrasound was determinant to suspect and consequently diagnose a rare condition as AL amyloidosis with multi-organ involvement, even if the clinical presentation of both patients was not specifically indicative for this disease.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Complications in a cohort of adult thalassemia major patients: cardiac and endocrinological involvement E. Cassinerio1, L. Zanaboni1, A. Roghi2, P. Pedrotti2, A. Milazzo2, G. Graziadei1, F. Brevi1, P. Pattoneri3, M.D. Cappellini1 1 Department of Internal Medicine, ‘‘Ca’ Granda’’ Foundation IRCCS, Univ. of Milan, Italy; 2CMR Unit, Department of Cardiology, Niguarda Ca’Granda Hospital, Milan, Italy; 3Department of Internal Medicine, Nephrology and Health Sciences, University of Parma, Italy

Introduction: Thalassemic syndromes are a heterogeneous group of haemoglobin disorders, characterized by a partial or complete suppression of the production of one or more globin chains. In thalassemia major (TM) patients (pts) regular blood transfusions from infancy are the life treating therapy. Iron overload and subsequent target organs damage are the results of regular red cells blood transfusions. During the last decade, the development of new iron chelators and new personalized chelation regimens led to an improvement of patient survival and of quality of life, reducing iron overload-related complications. Aim of the study: To evaluate the cardiac and the endocrinological complications in adult TM pts in different age cohorts. Patients and Methods: One hundred twenty eight TM pts (53 males/ 75 women, mean age 32 ± 6 years) underwent cardiac magnetic resonance (CMR) to assess myocardial iron load. CMR was performed at Cardiology and CMR Department ‘‘A. De Gasperis’’ at Niguarda Ca’ Granda Hospital in Milan, using a 1.5 Tesla MR scanner (Avanto Siemens, Erlangen). Normal cardiac T2* was defined [20 ms; T2* \20 ms indicated cardiac siderosis. History of cardiac events (arrhythmias, heart failure) and endocrinological complications (hypothyroidism, hypogonadism, glucose intolerance and diabetes) were detected. Results: Overall, the pre-transfusional mean hemoglobin (Hb) was 9.4 ± 0[7 g/dl and the median ferritin value was 961 ng/ml (range 240–14,821 ng/ml). The myocardial T2* was \20 ms in 47 pts (36.7%), and C20 ms in 81 pts (63.3%). Twenty-eight pts (21.9%) showed a history of relevant arrhythmias, 21 (16.4%) of heart failure: 39 (30.4%) pts were treated with cardiological therapies (ACEinhibitors, diuretics or antiarrhythmic drugs). In the overall population, hypothyroidism was present in 31 (24.2%) pts, hypogonadism in 107 (83.6%), glucose intolerance in 23 (17.9%) and diabetes in 22 (17.2%). Considering pts date of birth, all the cardiac and endocrinological complications were reported in table.

Parameters

Pts born before 1980 Pts born after 1980 (n.104) (n.24)

T2* \20 ms, n (%)

41 (39.4%)

6 (25%)

T2* [20 ms, n (%)

63 (60.6%)

18 (75%)

Arrhythmias, n (%)

27 (26%)

1 (4.2%)

Heart failure, n (%)

21 (20.2%)

0 (0%)

Hypothyroidism, n (%)

30 (28.8%)

1 (4.2%)

Diabetes, n (%)

22 (21.1%)

0 (0%)

Glucose intolerance, n (%) 20 (19.2%)

3 (4.2%)

Hypogonadism, n (%)

12 (50%)

95 (91.3%)

Discussion and Conclusions: Our data showed that the availability during the last 10 years of new chelation regimen (oral drugs) based on tailored chelation therapy significantly changed the incidence of

S243 myocardial iron overload and of the cardiac and the endocrinological complications. The younger patients had a striking reduction in the incidence of arrhythmias and heart failure; the endocrinological complications were importantly reduced. The goal in treating thalassemia major patients for the near future is to achieve a iron-related complications free survival.

Cardiac amyloidosis, a shifty disease. However…whoever seeks will find! S. Da Ros1, G. Tarquini1, M. Ammendola1, A. Crudeli1, M. Curione1, M. Francone2, M. Frustaci3, P. Lucia1, S. Matteoli1, M. Sellini1 1

Dipartimento di Medicina Interna e Specialita` Mediche; Dipartimento di Scienze Radiologiche, Oncologiche e AnatomoPatologiche; 3Dipartimento di Scienze Cardiovascolari, Respiratorie, Nefrologiche e Geriatriche, ‘‘Sapienza’’ Universita` di Roma, Roma, Italy 2

The myocardium and intramyocardial vessels are involved in most case of amyloidosis [1]. The seriousness of heart damage drives the prognosis in all cases. Sometimes the cardiac manifestations of amyloidosis are misinterpreted or confused with other cardiomyopathies [1]. Aim: The aim of our case-report is to emphasize the need of a quick diagnosis to ameliorate the very poor prognosis of the disease. Case report: G.C., a 58 years old asymptomatic woman, on February 2010 underwent for a routinary screening a resting ECG which showed negative T waves in inferior and lateral leads (Fig. 1). Previous ECG were normal. The clinical history was negative. The ECG stress didn’t show further modifications of ST-T. The 24-h dynamic ECG registration didn’t demonstrate arrhythmias. The echocardiogram displayed interventricular septal (IVS) hypertrophy (12.3 mm). On May 2010, at the admission to our department, she complained dyspnea after strong strains. The physical examination was negative. The ECG was unchanged. Plasma biomarkers of myocardial injury were increased little (myoglobin 164 ng/ml, troponin T 0.048 ng/ml), such remaining in following samples. Laboratory investigations revealed high total (237 mg/dl) and LDL (170 mg/dl) cholesterol values. In order to exclude ischemic disease, a coronary angiography was performed; it didn’t show stenosis. Echocardiogram (11 weeks after the first one) revealed increased myocardial echogenicity, a ‘‘sparkling’’ diffuse appearance, thickening of both ventricular walls (IVS 15 mm., posterior wall 14 mm.), global reduction of systolic function (ejection fraction 55%) without segmental deficits, diastolic dysfunction (IV degree) (Fig. 2). The cardiac magnetic resonance (MR) detected unhomogeneous delayed gadoliniun enhancement in meso-epicardium. The echocardiographic and MR patterns suggested a storage disease. The hystologic fragments from left ventricular walls were characterized by hypertrophic and hypotrophic fibres along with an homogeneous substance involving interstitium and intramural arteries which demonstrate apple-green birefringence after stained with Congo-red coloration and polarized light view. The immunohistochemical study was positive for k chains. The reported findings suggested the diagnosis of light chains amyloidosis (AL amyloidosis). The serum and urine immunofixation were positive for k chains monoclonal component. In the bone marrow 17% of plasma cells was present. The radiologic investigations didn’t show bone lesions. The diagnosis of AL amyloidosis secondary to myeloma was made. Other amyloid localizations were not detected. On June 2010, the patient manifested the first episode of acute heart failure. Over the next weeks a progressive deterioration of clinical condition occurred. Therapy with dexamethasone, furosemide and potassium canreonate was started. Then, the patient was treated with cyclophosphamide and bortezomib too. On September 2010, the cardiovascular symptoms and signs began to slightly improve.

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S244 Fig. 1

Fig. 2

We have presented this case for its particularity, the lack of symptoms although serious cardiac injury. Chemotherapy targeting clonal plasma cells that produce the monoclonal amyloidogenic Ig light chains can arrest amyloid formation and lead to regression of deposits and survival improvement, despite the amount of cardiac amyloid deposits remains apparently unaltered [2]. Accordingly, it can be emphasized to take into account cardiac amyloidosis either when the systemic disease is present or when a generic cardiomyopathy is found, in order to avoid misinterpretations and related tardive diagnosis which worsen the prognosis. References 1. Falk RH, et al. Prog. Cardiovasc Dis. 2010;52:347–61 2. Palladini G, et al. Blood. 2006;107:3854–8

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 and blood marrow aspirate were carried out by cyto-morphologic and cytogenetic analysis. The patient’s peripheral-blood smear revealed only mild aniso-poichilocytosis, mild microcytic, hypochromic erythrocytes, rare target cells and nucleated orthochromatic erythroblasts. The bone marrow aspirate revealed a secondary dyserythropoiesis PAS-negative with apparent absence of ring sideroblasts because of the large amount of peripheral-blood cells contamination. Considering the iron overload, the microcytic hypochromic anaemia and the prevalence of the male gender affected, we suspected an X-linked congenital sideroblastic anaemia. This form of anaemia is mainly due to ALAS2 gene mutations. By PCR and direct sequencing we identified on ALAS2 gene a new mutation c.1231C[A (R411S) in hemizygosis in the propositus. The patient was treated with vitamin B6 (pyridoxine) showing a significant increase of haemoglobin levels. Also his cousin was revaluated, and diagnosed as well as affected by X-linked congenital sideroblastic anaemia and treated in the same way; he decreased progressively the transfusion requirement and consequently iron overload. Sideroblastic anaemias are heterogeneous congenital or acquired disorders characterized by a variable population of hypochromic red cells in the peripheral blood and by ring sideroblasts in the bone marrow due to pathological iron deposits in mitochondria of erythroid precursors. Among the congenital sideroblastic anaemias the most common form is the X-linked sideroblastic anaemia, caused by mutations of delta-aminolevulinic acid synthase 2 (ALAS2), the enzyme that catalyses the first and regulatory step of heme synthesis in erythroid precursors. New forms have been recognized as being linked to the deficient function of mitochondrial proteins involved in iron-sulphur cluster biogenesis, such as ABCB7 and GLRX5 and of mitochondrial transporter as SLC19A2. Local mitochondrial iron overload is present in all sideroblastic anaemias, whereas systemic iron overload occurs mainly in the forms due to primary or secondary deficiency of ALAS2. This case suggests that the presence of anaemia in several members of a family requires an adequate differential diagnosis. A misdiagnosis may affect the treatment and the related complications. Although Thalassemia syndromes are the most common hereditary anaemias in Italy, any other possible defect (membrane, enzyme, heme pathway) must be considered in differential diagnosis. The molecular analysis of most of the erythrocyte proteins is available in specialized laboratory that may be consulted in case of unclear cases, before starting a chronic treatment.

Congenital microcytic anaemia does not always mean thalassemia G. Graziadei, V. Brancaleoni, E. Di Pierro, F. Granata, M.D. Cappellini Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Dipartimento di Medicina Interna, Universita` degli Studi di Milano, Italy A 53 year old man of Italian origin was admitted to our out-patient service because of worsening anaemia (Hb 8 g/dl) and iron overload (ferritin: 994 ng/ml on iron chelation therapy). At 18 years of age, he was clinically diagnosed as affected by Thalassemia Intermedia because of moderate microcytic anaemia (Hb 9.5 g/dl, RBC 5.88 9 106/mm3, MCV 58.8 fl, RDW 30.4, with normal leucocytes and platelets count), mild splenomegaly and iron overload. Family history was known for Thalassemia, infact his brother and his male cousin were regularly transfused as Thalassemia Major patients. The brother died at the age of 20 years and another male cousin died in childhood both for complications of anaemia not better defined. The propositus required only occasional transfusions during infectious episodes. In order to characterize the type of Thalassemia we revaluated haematological and molecular data. Surprisingly HPLC values, haemolysis indices, alfa and beta globin clusters resulted normal: for this reason the diagnosis was reconsidered. Peripheral-blood smear

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Anemia in the elderly: evaluation in consecutive patients admitted to an Internal Medicine Unit M. Migone De Amicis, I. Motta, C. Hu, F. Minonzio, S. Damanti, E. Colella, L. Duca, G. Fabio, M.D. Cappellini U.O. Medicina Interna 1A, Fondazione IRCCS Ca` Granda Ospedale Maggiore Policlinico, Milano, Italy Introduction: Anemia is a relevant problem in hospitalized patients and it is an under-diagnosed condition in elderly, mostly perceived as a mere consequence of aging or a disease marker. Although anemia has often been considered a normal consequence of aging, the pathophysiology of such an age-related decline in erythrocyte production is not yet fully understood, and efforts to understand anemia in elderly have become a major target of research interest. To some extent the decreased hemoglobin level can be explained with nutritional deficiency, anemia of chronic inflammation or comorbidities in many anemic elderly, however does not explain all the cases. Aim: The aim of this study was to evaluate the prevalence of anemia in hospitalized patients aged 65 years and older and to feature its etiology and its relationship to comorbidities.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392

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Materials and Methods: Anemic patients admitted to Medicina Interna 1A at Fondazione Ca’ Granda Policlinico were recruited consecutively for 6 months starting from 15th October 2010 to April 2011 excluding those with congential hemoglobinopathies and the onco-hematological disorders. We evaluated the CBC, reticulocyte number, iron pattern, folate, vit.B12 levels and hemolysis index (LDH, bilirubin and haptoglobin) to define the anemia. Normal values were considered according to that of the hospital laboratory. Anemia was defined according to WHO criteria (Hb \ 12 g/dL for women and Hb \ 13 g/dL for men). EPO was measured by an IBL International GMBH ELISA kit in a subset of anemic patients and normal controls matched for age and sex (35 anemic, 43 not anemic). Results: The results are summarized in Table 1. 215 patients [65 years old were admitted during the 6 months of the study; 22 were excluded because of congenital hemoglobinopathies or oncohematological disease. 92/193 were anemic (48%); 53 women (58%) and 39 men (42%). The anemia was mainly normocytic (65%); 22/92 (23%) had a macrocytic anemia and for 8 of them we proved a folate and/or vit B12 deficiency; 10/92 had a microcytic anemia, with transferrin saturation\15% in 7 patients. The reticulocyte index was available in 75 patients and it was lower than 1 in 48/75 (64%) patients. 23/92 patients underwent an endoscopic evaluation (gastroscopy and/or colonoscopy) and in 9 cases it explained the origin of the anemia, showing 3 cases of diverticulosis, 3 case of teleangectasias and 3 cases of atrophic gastritis. In 1 patient the exam revealed esophageal varices, without signs of bleeding. 17/30 (56%) patients with a non-hematological neoplasia were anemic; 17/28 (60%) patients with chronic liver disease were anemic. EPO levels did not show significative difference between anemic and non anemic. Discussion: Anemia is a common condition in elderly patient: 48% of the [65 years old patients admitted to our department were anemic, between them 30/92 (33%) required blood transfusions. Considering the etiology of anemia we observed that 48/92 patients had a nutritional deficit mainly due to iron deficiency than Folate or vit B12 deficiency: 47/92 had transferrin saturation level lower than 15%. Only 10 patients had a combined deficiency of iron and B12 and folate. In 64% of the patients the reticulocyte index was lower than 1, suggesting a reduced bone-marrow production not related to a defined hematologic disorder but that elicits a physiological hypofunction. Conclusions: Anemia is an emerging public health problem, requiring a an ever-greater allocation of health care resources since the number of elderly patients is progressively increasing in the following years.

TOT

Anemic patients over 65 years old

Microcytic anemia

92/193 (48%) 10/92 (11%)

Macrocytic anemia

Normocytic anemia

22/92 (24%)

60/92 (65%)

PCR [ 0.5 mg/dl

73/92 (79%)

7/10 (70%)

15/22 (68%)

51/60 (85%)

Folic acid and/or B12 deficit

24/92 (26%)

2/10 (20%)

8/22 (36%)

14/60 (23%)

Transferrin saturation \ 15%

47/92 (51%)

8/10 (80%)

5/22 (23%)

34/60 (57%)

Reticulocyte index \ 1

48/75 (64%)

5/6 (83%)

9/17 (52%)

34/51 (66%)

EPO mean value ± DS

30.5 ± 37.3

124.7 ± 112.2 14.8 ± 7.4

34.2 ± 41.2

Prolonged PT and aPTT in a patient with severe proteinuria I. Motta1, A. Artoni1, M. Migone De Amicis1, C. Hu1, B. Brezzi2, F. Minonzio1, M.D. Cappellini1 1 Department of Internal Medicine; 2Division of Nephrology, Dialysis, and Renal Transplant, IRCCS Ca` Granda Ospedale Maggiore Fondazione Policlinico, Universita` degli Studi di Milano, Milano, Italy

A 70 year old woman was admitted to our medical unit because of severe bilateral foot and leg edema and peripheral paresthesias, that gradually developed during the last 3 months. The patient had a history of hypertension treated with calcium-antagonist, a well-controlled type 2 diabetes (glycated Hb 6.4%) treated with oral hypoglycemic drugs for 6 years. Ten months before admission blood and urine analysis, ophthalmologic examination and US Doppler of legs did not show any sign of organ damage. Six months before admission she underwent surgery for tunnel carpal syndrome. At admission blood pressure was normal and on physical examination she had grade 3 peripheral bilateral edema. Blood laboratory examinations revealed renal insufficiency (serum creatinine 1.38 mg/dl, GFR MDRD 40 ml/min/ 1.73 m2, urea 91 mg/dl) that rapidly worsened with furosemide, severe hyperkalemia, and hypoalbuminemia with normal liver function. Furosemide was stopped. We observed a progressive increase of weight from 89 to 92.5 kg. A nephrotic proteinuria was detected (13.1 g/24 h) associated to mild microscopic hematuria. The known diabetes couldn’t explain such rapid progression of renal failure and severity of symptoms, thus we consulted a nephrologist and a renal biopsy was advised. She had prolonged PT ratio (2.07) and aPTT ratio values (1.67), that were normal 6 months previously (PT1.2, aPTT 0.9). We suspected a coagulation disorder due to nephrotic syndrome, characterized by loss and subsequent deficiency of smallest clotting factor. Before performing the renal biopsy we investigated clotting factor activity. The results showed a normal activity of all clotting factors (II, V, VII, IX, XI, and XII), but an unexpected severe deficiency of factor X (7%), corrected after mixing test. At this point we suspected amyloidosis, considering the nephrotic syndrome, the recent history of tunnel carpal syndrome and the described association between factor X deficiency and amyloidosis. Umbilical fat biopsy was performed. Congo red stain resulted positive confirming the suspected diagnosis. Echocardiography showed a dilatation of left ventricle with normal systolic function. Because of patient age and rapid progression of symptoms and coagulopathy, systemic light-chain amyloidosis (AL) was suspected and confirmed by the presence of free light chain k in serum (k/k ratio 8.17). Bence-Jones protein was negative, serum electrophoresis, immunoglobulins were normal; beta2-microglobulin elevated 10.9 mg/L (v.n. 0.8–2.2). Bone marrow biopsy was performed, after infusion of prothrombin complex, showing 10% of plasma cells in bone marrow. FX increased to 30% at 1 h and 18% at 4 h, indicating shorter half life of FX. The patient was treated in the Division of Nephrology with steroid and cyclophosphamide, interrupted for side effects such as pancytopenia and urinary tract infection. Renal function, despite therapy, rapidly worsened developing uremia and required hemodialysis. Because of the severe nephrotic syndrome blood pressure reached very low levels leading to an angina pectoris episode. The incidence of factor X deficiency in systemic light-chain amyloidosis varies from 8 to 14%; it’s the most frequent cause of bleeding in these patients. Deficiency is due to absorption of Factor X by fibrils of amyloid composed by immunoglobulin light chain.

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S246 Multiorgan failure in a patient with hemophagocytic syndrome D. Santovito1, D. Lomazzo1, A. Gentile2, V.O. Palmieri1, G. Palasciano1 1 Internal Medicine ‘‘A. Murri’’; 2Pathology Unit, University of Bari, Italy

Background: The hemophagocytic syndrome (HS) is a rare and serious disorder of immuno-regulation, characterized by systemic notmalignant proliferation and multi-organs infiltration of histiocytes that have an unpredictable hemophagocytosis in bone marrow and/or in the reticulo-endothelial system [1]. The immune dysfunction consists of a deficit of T- and NK-cells cytotoxic functions associated to hyperactivation of T-cells and macrophages and a high production of pro-flogistic cytokines. Two main forms of hemophagocytic syndrome exist: primitive (familiar hemophagocytic lymphohistiocytosis) and secondary form (reactive HS). The secondary forms are related with infections, immunodeficiency, tumours, autoimmune diseases and lymphomas. Case report: White male patient, 23 years old, farmer, fracture of left arm at 5 years age, in apparent good health until March 2011 when he was admitted to the Hospital of Terlizzi (Bari) because since 1 month he had fever unresponsive to antibiotic and antipyretic therapy, iporessia and asthenia, nausea, constraining chest pain. After 5 days during which the conditions of the patient remained unchanged he was transferred to our Unit. Physical examination: absent declive oedema, absent palpable nodes, bilateral basal reduced vesicular murmur, enlargement of liver and spleen. Biochemical examinations at the admission: AST 231 U/L, ALT 147 U/l, albumin 2.9 g/dl, WBC 1,830 (60% N, 35% L), PLT 142,000/mmc, normochromic normocytic anemia (HB 12.8 g/dl), serum ferritin 16.452 ng/ml, PT INR 1.27, PTT ratio 1.31, D-dimers 17030 lg/L, fibrinogen 165 mg/dl, LDH 2216 U/l, b2-microglobulin 8.3 lg/ml. The following hypotheses were formulated: neoplastic haematologic disorder, infection (viral, bacterial, mycotic), autoimmune disease (enclosing granulomatous diseases). We performed virological, bacteriological and mycotic exams (negative), screening for autoimmune disease, e.g. erythematosus systemic lupus, that was also negative; the examination of bone marrow biopsy concluded for reactive bone marrow while lymphocytes phenotyping showed mild hyperactivity of T cells. Bone marrow aspirate and peripheral blood morphological examination were negative. Thorax and abdomen CT exhibited a 2 cm right lung cyst, bilateral pleural, pericardial and abdominal light effusion; abdomen MR documented in both hepatic lobes peripheral areas of hypervascularity, compatible with areas of abnormal perfusion, spleen enlargement, small amount of ascitis. US was coincident with CT. We also performed liver biopsy that put in evidence macro-and microvesicular steatosis with hepatocellular marked suffering, presence of engulfing histiocytes with an aspect of sinusoidal hemophagocytosis, eosinophils, lymphocytes, myeloid blasts similar precursor cells. The preliminary diagnosis of a neoplastic proliferative disorder was therefore formulated. Empirical wide-range antibiotic therapy was early started in association to steroid therapy after exclusion of infective diseases. After a week of hospital stay, we observed a progressive clinical deterioration and the biochemical evidence of an acute disseminated intravascular coagulation. For this reason, we started therapy with vitamin K, antithrombin III, ev albumin (the patient refused plasma derivatives for religious reasons). In few hours, we observed a rapid onset of multiorgan failure (MOF) syndrome with involvement of liver, pancreas, kidney and lungs, that evolved to respiratory failure, hypovolemic shock and metabolic acidosis that made it necessary endotracheal intubation. The patient died after about 6 h.

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 The autopsy confirmed the dramatic impairment of parenchymal organs function and permitted the definitive diagnosis of hemophagocytic syndrome with hepatic and splenic localization as primum movens of the multiorgan failure syndrome. Conclusion: The HS is a rare disease with a poor prognosis: the clinical course is rapidly fatal and sustained remissions are rarely achieved. Furthermore, antemortem diagnosis of this disease is challenging because there is no pathognomic features or markers. The unique reliable mean of diagnosis remains tissue biopsies of any involved organ. The HS should be considered in patients with multisystemic manifestations without obvious etiology and any effort should be made in order to early confirm the diagnosis. Reference 1. Expert Rev Clin Immunol. 2010;6(1):137–54

An unusual non-Hodgkin lymphoma foot plantar localization G. Spoletini1, D. Spinelli1, F. Cantoni1, M. Migone De Amicis1, F. Minonzio1, C. Hu1, M. Goldaniga2, M.D. Cappellini1 1

Dipartimento Di Medicina Interna, Universita` degli Studi e Fondazione IRCCS Policlinico, Milano; 2UO Ematologia 1/CTMO, IRCCS Fondazione Policlinico, Milano, Italy We report the case of a 84-year-old man, who came to our attention because of swelling on his right-foot plantar surface, persistent for the last 15–20 days, causing pain and discomfort while walking. Before admission, the patient underwent a right foot MRI that showed an expansive process with non well-defined margins (6.4 9 4.9 9 12.3 cm) infiltrating the plantar fascia and the subcutaneous tissue, and involving the foot flexor, the posterior tibial and the peroneal tendons. Patient’s clinical history included transurethral resection (TUR) for prostatic adenoma 15 years before, primary arterial hypertension, aortic endoaneurismectomy, bladder urothelial carcinoma. During 2009 patient underwent orchiectomy because of bilateral testicular mass: histological examination was compatible with large-B-cell non Hodgkin lymphoma (NHL) exclusively localized to both testis. After orchiectomy oncological stadiation was negative. The administration of CNS prophylaxis in addition to systemic chemotherapy was omitted for medical decision, according to patient’s will. The patient was treated with 4 cycles of chemotherapy (CHOP21), interrupted, in persistent complete remission, for worsening clinical conditions, in particular due to appearance of lower limbs polyneuropathy. Rituximab was withdrawn during the first chemotherapy cycle for a severe allergic reaction. On admission to the hospital the patient reported at rest pain at the plantar surface of his foot, with frequent exacerbations while walking. The physical examination showed a swollen and tender right foot due to the presence of a ligneous mass extending on the medial border from the metatarsus to the calcaneus; the mass was adherent and the overlying skin had initial ulcerations. The general examination was normal but hepatomegaly. Blood laboratory tests revealed a mild normocytic normochromic anemia and a mild elevation of serum creatinine and of acute phase reactants. The serum protein electrophoresis showed a double IgM monoclonal component and b2microglobulin was 3.4 mg/L (n.v. 0.8–2.2 mg/L). An ultrasound (US) foot exam showed a hypoechogenic moderately vascular solid dishomogeneous lesion. An US-guided biopsy of the lesion was performed: cytofluorometry analysis showed that the majority of the cells were CD45-, with 15% made of large cells (monocytoid scatter) CD45+ CD19+ CD20+ CD10- CD5- CD30-, sIg-. Histopathological finding was diagnostic for large-B-cell NHL with proliferative index value of 80–90%. To define the clinical stage of the disease a CT scan, an abdominal US and a CT-PET scan were performed. The

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 head, neck and chest CT scans were negative for suspected lesions and adenopathies; the abdominal CT images revealed a thickened wall of an ileal segment; no adenopathy was detected. The abdominal US confirmed mild wall thickening (0.5 cm) involving the last ileal segment over a 7 cm length. The CT-PET scan showed an increased metabolism both at the foot lesion, with a maximum SUV of 41, and at the ileal segment, with a maximum SUV of 35. Considering the early relapse, age and comorbidities the patient was treated with a modified, dose adapted DHAP. At discharge a partial regression of the mass was observed, and no early toxicity neither adverse reactions were recorded. Testicular large-B-cell NHL is an aggressive extranodal lymphoma characterized by high risk of relapses even when localized at the diagnosis; orchiectomy on the side of disease is usually performed to obtain diagnostic tissue, however orchiectomy alone is not a sufficient treatment. Testicular lymphoma often disseminates to other extranodal organs, such as controlateral testis, central nervous system (CNS), lung, pleura, Waldeyer’s ring and soft tissue; however the foot plantar localization occurred in our patient, is a very rare and unusual localization.

Thrombosis and Hemostasis A widespread muscular pain in a 29 year old woman suffering from sickle cell disease S. Avallone1, R. Gente1, M. Di Palo1, A. Ilardi2, R. Esposio1, P. Strazzullo1 1 Dipartimento di Medicina Clinica e Sperimentale, Clinica Medica, AOU Policlinico Federico II, Napoli, Italy; 2Dipartimento Emergenza-Accettazione, UODS di Medicina d’Urgenza, AORN ‘‘A.Cardarelli’’, Napoli, Italy

In February 2011, a 29 year old woman is admitted to the Emergency Room of the Hospital ‘‘A. Cardarelli’’ in Naples, because of a widespread intense pain, especially to the lower limbs, which occurred suddenly about an hour before. The patient, suffering from sickle cell disease and deaf-mute since birth, is awake to the clinical examination (GCS = 15), and in good hemodynamic compensation [valid and rhythmic heart tones (HR = 78 bpm), no peripheral edema, no jugular venous distension], with ascending right lung base and painless abdomen at the palpation. The skin has a yellowish tinge and she denies fever. The ECG is within the normal limits; the blood gas analysis in room air shows an hypoxemic respiratory failure (pO2 = 56 mmHg, pCO2 = 42 mmHg) with a SpO2 = 89% (pulseoximeter), susceptible of correction with O2-therapy (FiO2 = 0.40). Laboratory analyses at admission show: Hb = 8.6 g/dL, RBC = 2.710.000/mmc, WBC = 14.630/mmc, Bil Tot = 1.6 mg/dL, Bil Ind = 1.40 mg/dL, LDH = 640 UI/L, no signs of kidney damage. Pain does not responds to NSAID, but it is mitigated by opioids. The chest X-ray highlights an abnormal texture and confirm the ascending right lung base. To the subsequent clinical examination, the patient is confused and disoriented: brain CT is negative. The hematologists decide to transfuse two filtered and washed packed red blood cells bags, suspecting a vaso-occlusive complication. About 6 h after the transfusion, an intense chest and abdominal pain appears with recurring episodes of vomit. Hypotension (SBP/DBP = 90/55 mmHg), with tachycardia in clinostasis (HR = 108 bpm),

S247 polypnea and abdominal tenderness at deep palpation, mostly in the lower quadrants, appear. The laboratory analyses show: Hb = 10 g/dL, WBC = 20.900/mmc, Bil Tot = 3.30 mg/dL, Bil. Ind = 2.20 mg/dL, Alb = 2.8 g/dL, AST = 552 UI/l, ALT = 359 UI/l, ALP = 285 UI/l, GGT = 79 UI/I, LDH = 8530 UI/I, CPK = 509 UI/I, Troponin I = 9.56 ng/mL, Fibrinogen = 624 mg/dL, INR = 1.32, Ca++= 7.6 mg/dL, Phosphorus = 6.2 mg/dL, Cr = 1.30 mg/dL, BUN = 66 mg/dL. The hemoglobin electrophoresis indicates high levels of HbS (45%) and of HbF (13.9%). Assuming an acute abdominal disease, an ultrasonography is performed. It shows fluid relaxation of some intestinal loops in the pelvis, hepatomegaly, pancreas in the normal limits, a normal volume spleen with multiple and widely distributed hypoechoic areolae. A nasogastric tube is placed and thick bile is drained. Ejection Fraction is preserved (65%) to the echocardiogram, with right ventricular dilatation, PAPs 60 mmHg and paradox motion of the interventricular septum. Meanwhile, blood tests and blood gas analysis show a further deterioration: Bil Tot (3.20 mg/dL), Bil Ind (2.00 mg/dL), AST (4470 UI/I), ALT (2302 UI/I), ALP (286 UI/I), GGT (91 UI/I), LDH (21337 UI/I), CPK (696 UI/I), BUN (111 mg/dL), D-dimer = 5,305 ng/ml, reduced Troponin I (5.30 ng/mL), pO2 = 75 mmHg, pCO2 = 34 mmHg and SpO2 = 95% (in oxygen therapy, FiO2 = 0.50). The possible diagnosis of Pulmonary Embolism is supported by a Well Score of 4.5. The chest CT-Angiography displays multiple defects of thromboembolic opacification: the lumen of the right lower lobe bronchus appears to be full of dense mucoid material with an area of parenchymal consolidation and contextual air bronchogram. A lower limbs venous Doppler ultrasonography shows a clot partially occluding the proximal segment of the right popliteal vein. Other two filtered and washed packed red blood cells bags are transfused, a wide spectrum antibiotic therapy is prescribed and it is started a specific treatment (LMWH at therapeutic dose, early imbricated with Warfarin sodium) with graduated elastic compression of the lower limbs. The progressive improvement of the patient’s clinical conditions allows the execution of a bronchoscopy, that finds bile in the right basal pyramid, probably from aspiration. In the 40th day, she is discharged from the hospital with the diagnosis of ‘‘Thromboembolic Venous Disease in patient suffering of Sickle Cell Disease’’.

Risk of recurrence in patients with pulmonary embolism: predictive role of d-dimer and of residual perfusion defects on lung scintigraphy C. Cenci, D. Poli, E. Grifoni, E. Antonucci, C. Arcangeli, D. Prisco, R. Abbate, M. Miniati SOD Malattie Aterotrombotiche, Azienza Ospedaliero-Universitaria Careggi, Firenze, Italy Purpose: The stratification of recurrence risk after a first episode of venous thromboembolism (VTE) is an important topic of recent research. This is of particular clinical relevance in patients who experienced pulmonary embolism (PE) for the risk of developing chronic thromboembolic pulmonary hypertension and for the mortality related to PE. Elevated D-dimer levels after withdrawing oral anticoagulant treatment (OAT) are predictive of recurrence, but it is still unknown if residual perfusion defects (PD) on lung scintigraphy are related to recurrent PE. Aim of our study was to evaluate whether PD are associated with the risk of recurrence.

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Methods: We prospectively followed 102 consecutive patients who survived a first episode of objectively confirmed PE, with or without deep vein thrombosis. After at least 3 months of OAT, treatment was withdrawn and the patients followed to detect VTE recurrences. D-dimer levels were evaluated 1 month after OA withdrawal and perfusion lung scan (P-scan) was performed. PD affecting 10% of the pulmonary vascular bed or greater were considered relevant. Table 1 Patients characteristics N (percent, or range) Patients

102

Follow-up (patient-years)

237.3

Median follow-up (months)

22 (1–120)

Males

49 (43.4)

Median age (years)

60 (16–87)

Unprovoked PE

74 (65.5)

Isolated PE

46 (41.1)

Oral contraceptives (for females)

17 (26.6)

Congenital thrombophilia

20/100 (20)

Median OAT duration (mo)

12 (4–72)

Recurrent VTE (1 fatal)

13/102 (12.7)

Rate of VTE recurrence (9100 pt-years)

5.4

Median time of recurrent VTE (mo)

6 (1–81)

PD on P-scan

21 (19.4)

Elevated D-dimer levels

31 (27)

Results: Elevated D-dimer levels were significantly associated with VTE recurrence (p = 0.002), but no association was found between PD and recurrences (p = 0.5). Conclusions: We confirmed the positive predictive value of elevated D-dimer levels for recurrent VTE. Residual PD on lung scintigraphy are not predictive of recurrence.

under chronic daily treatment with 100 mg ASA. 25 healthy subjects (HS), treated with 100 mg ASA for 4 days, were also studied. Methods: Platelet aggregation (light transmission aggregometry, LTA) induced by 1 mM arachidonic acid (AA) or 5 lg/mL collagen were measured in platelet-rich plasma (PRP), prepared from whole blood anticoagulated with sodium citrate, 2 and 24 h after ASA. PA was also measured in hirudin-anticoagulated PRP and whole blood by impedance aggregometry (Multiplate) 2 h after ASA. TxB2 was measured in supernatant plasma of whole blood and PRP after stimulation with AA, and in serum. Results: Experiments by LTA. AA-induced platelet aggregation was completely abolished in all subjects, except in 9 DM-CAD (PA between 1 and 6%), 18 ND-CAD (1–7%) and 7 HS (1–9%). Collageninduced PA was slightly, but significantly lower in DM-CAD, compared to the other 2 groups at 24 h, but not at 2 h. Experiments by Multiplate. Collagen- or AA-induced platelet aggregation in whole blood or PRP was not significantly different among the 3 groups. AAinduced PA in whole blood was higher than in PRP: the in vitro addition of the thromboxane receptor antagonist SQ29458 (5 lM) to whole blood inhibited AA-induced PA in all groups by about 40%. Measurement of TxB2. No statistically significant differences in serum TxB2 were found among the 3 groups, both in the 2 h (DMCAD 3.4 ± 3.0 ng/mL; ND-CAD 3.1 ± 2.8; HS 2.5 ± 1.8) and the 24 h samples (3.9 ± 6.9; 3.5 ± 4.0; 3.0 ± 2.9). After stimulation with AA, the levels of TxB2 in supernatant plasma from whole blood (DM-CAD 77.1 ± 38.0 ng/mL; ND-CAD 73.8 ± 50.3; HS 92.7 ± 37.0) were higher than in supernatant plasma from PRP (4.2 ± 7.1; 3.9 ± 5.0; 3.1 ± 2.3) without any statistically significant difference among the 3 groups of subjects. Conclusion: We found no evidence of impaired response to ASA in DM-CAD, compared to ND-CAD and HS. ASA did not completely inhibit AA-induced platelet aggregation and thromboxane production in whole blood from all subjects, suggesting that extraplatelet sources of thromboxane may stimulate platelets even when platelet COX-1 is well inhibited by ASA.

Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy N. Ferrante1, M. Di Nisio1, A. Ws Rutjes2, H.-M. Otten3, F. Cuccurullo1, E. Porreca1 1

Acetylsalicylic acid inhibits thromboxane A2 production and thromboxane A2-dependent platelet function equally well in diabetic and non-diabetic subjects E.A. Femia, M. Pugliano, G.M. Podda, C. Razzari, M. Spina, F. Lombardi, M. Cattaneo Universita` degli Studi di Milano, Azienda Ospedaliera San Paolo, Milano, Italy Background: Acetylsalicylic acid (ASA), which inhibits platelet cyclooxygenase-1 (COX-1) dependent thromboxane A2 (TxA2) formation, decreases cardiovascular events in patients with coronary artery disease (CAD). According to some reports, patients with type-2 diabetes mellitus (DM) may be less responsive to ASA than non-DM patients. Aim: We compared the platelet production of thromboxane B2 (TxB2), a stable TxA2 metabolite, and platelet aggregation (PA) in 50 type-2 DM CAD patients and 50 non diabetic (ND) CAD patients

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Department of Internal Medicine, University G D’Annunzio, Chieti, Italy; 2Division of Clinical Epidemiology and Biostatistics, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; 3Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands Venous thromboembolism (VTE) often complicates the clinical course of cancer disease. While the risk is further increased by chemotherapy, the safety and efficacy of primary thromboprophylaxis in cancer patients treated with chemotherapy is uncertain. The objective of this review is to assess the efficacy and safety of primary thromboprophylaxis in ambulatory cancer patients receiving chemotherapy. A comprehensive search for studies of thromboprophylaxis in cancer patients up to August 2010 was conducted in the Cochrane Central Register of Controlled Trials (CENTRAL) up to Issue 2, 2011 and May 3rd 2011 for the Specialised Register. Randomised controlled trials (RCTs) comparing unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), vitamin K antagonists (VKA), direct thrombin inhibitors, direct factor Xa inhibitors or mechanical intervention to no intervention, placebo or comparing two different

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 anticoagulants were considered. Data were extracted on methodological quality, patients, interventions and outcomes including symptomatic VTE (primary outcome), (major and minor) bleeding, all cause mortality, asymptomatic VTE, symptomatic arterial thromboembolic events, quality of life, (serious) adverse events. Of 215,199 identified citations eight RCTs were considered. None of the RCTs tested UFH, fondaparinux, direct factor Xa inhibitors or mechanical interventions. Overall, the risk of bias was low in most of the studies. LMWH significantly reduced the incidence of symptomatic VTE [relative risk (RR) 0.62, 95% confidence interval (CI) 0.41–0.93) with no evidence of heterogeneity (I2 = 0%). The number needed-to-treat to prevent a symptomatic VTE was 50. LMWH was associated with a 60% increase in major bleeding, although not statistically significant (RR 1.57, 95% CI 0.69–3.60). There was a 45% reduction in overall VTE (RR 0.55, 95% CI 0.34–0.88), while for symptomatic pulmonary embolism (RR 0.63, 95% CI 0.21–1.91), asymptomatic VTE (RR 0.64, 95% CI 0.27–1.54), minor bleeding (RR 1.04, 95% CI 0.76–1.42) and 1-year mortality (RR 1.04, 95% CI 0.92–1.16) did not differences between LMWH and controls were not statistically significant. The effect of warfarin on preventing symptomatic VTE was not statistically significant (RR 0.14, 95% CI 0.02–1.18). Antithrombin, evaluated in one study on pediatric patients, had no significant effect on VTE nor major bleeding. No studies considered quality of life, heparin-induced thrombocytopenia and osteoporosis as study outcomes. Primary thromboprophylaxis with LMWH significantly reduces the incidence of symptomatic VTE in ambulatory cancer patients treated with chemotherapy. However, the lack of power hampers definite conclusions on the effects on major safety outcomes and symptomatic pulmonary embolism which mandates additional studies to determine the risk/benefit ratio of LMWH in this setting.

Myocarditis in a patient with antiphospholipid syndrome A. Guida, A. Tufano, A. Coppola, M. Di Palo, A. Russolillo, P. Ierano`, G. Quintavalle, A. Nardo, A.M. Cerbone, G. Di Minno Department of Clinical and Experimental Medicine, University ‘‘Federico II’’ of Naples, Italy A 52 years-old-man presented worsening dyspnoea and chest pain. He suffered by arterial-hypertension and previous deep venous thrombosis. Clinical examination and electrocardiograms revealed pulmonary oedema. At Echocardiogram: global hypokinesia, decreased LV ejection function (LVEF 30%) pulmonary hypertension (59 mmHg), and pericardial effusion; Troponin-I, CK-MB were mildly positive. Laboratory examination: anemia, leukocytosis; coagulation PT 22% INR 2.86 and APTT 218 APTT Ratio: 7, fibrinogen and D-dimers increase, FDP were negative, no active bleeding. He was referred to our Reference Centre for Coagulation disorders, the APTT mixing test did not correct, LA Ratio: 4.0 and Antiphospholipids mildly positive. He continued standard therapy for acute heart failure. The coronary angiogram revealed normal coronary anatomy. Immunological tests for infective myocarditis were negative, thyroid function was normal. ANA were mildly positive, ENA, Anti-ds-DNA, were negative; diagnosis of autoimmune myocarditis was done. Prednisone (0.5 mg/kg daily) were started and 4 weeks later a cardiac function amelioration (LVEF *35–40%) was observed. Endoscopies and CT-scan excluded a neoplasm, but coagulation abnormalities persisted, we performed an antiprothrombin antibodies ELISA assay, showing a strong positivity for such antibodies, Corticosteroids were progressively interrupted. In a 1 year follow up autoimmunity and coagulation tests were analogue while cardiac output was improved. Antiphospholipid syndrome is

S249 characterized by venous and arterial thrombosis and obstetric complications with high levels of antiphospholipids antibodies (APA), in this setting cardiac involvement concern coronary artery disease, rather than endocarditis. We describe a rare case of myocarditis in primary syndrome, characterized by a strong LA positivity and high titer antiprothrombin antibodies without thrombotic event.

Hypereosinophilia as aggravating factor for ischemic heart disease: a case report R. Rossio, A. Maino, B. Ferrari, M. Cugno, A.V. Marzano, A. Tedeschi Ca’ Granda IRCCS Ospedale Maggiore Policlinico di Milano, Milano, Italy In October 2010, a 69 year-old man presented to the emergency department of our hospital for acute chest pain radiating to his left arm and to the back, persisting from 2 h. The same symptom with the same features had occured in the previous day. He had a history of chronic ischemic heart disease started in 2007, when he underwent multiple percutaneous coronary interventions in the circumflex artery and proximal left anterior descending artery with placement of baremetal stents. In august 2010, cardiac catheterization was performed because of persisting angina: total occlusion of the distal right coronary artery was demonstrated and treated with placement of a drugeluting stent. In spite of this percutaneous coronary intervention, the patient remained symptomatic for unstable angina. In September 2010, a coronary computed tomography was performed and no coronary flow impairment was shown. A microvascular angina was suspected and beta blockers were substituted with the calcium antagonist diltiazem. Furthermore, the patient suffered from asthma, dyslipidemia, sideropenic anemia and had a familial history of ischemic heart disease. No other risk factor was evident. The patient was taking acetyl-salicylic acid, clopidogrel, diltiazem, nitrates, perindopril, and inhaled fluticasone plus salmeterol for asthma. At admission, blood pressure was 120/70 mmHg, the pulse rate was 70 beats/min, peripheral oxygen saturation 96% while breathing ambient air. His physical examination was normal. ECG showed non specific ST alteration. Laboratory investigations revealed an increase of myocardial necrosis markers (troponin T 0.09 ng/ml, normal values \0.02). The patient was treated with low molecular weight heparin, nitrate, protonic pump inhibitors and was admitted to intensive cardiac care unit (ICU). Routine laboratory analyses were normal except for marked eosinophilia (eosinophil absolute count number 4,000/ll). Troponine T progressively decreased during ICU stay. Ranolazine was introduced for the management of unstable angina and the patient was transferred to our unit because of eosinophilia. A detailed case history revealed the presence of elevated eosinophil count at least from 2008 when repeated white blood cell counts showed persisting hypereosinophilia (range 35–46%). To investigate the origin of the increased eosinophil count, we screened the patient for parasitoses and allergic and autoimmune diseases that were excluded. Anti-neutrophil cytoplasm antibodies were negative. Bone marrow biopsy and aspirate were performed and showed a marked eosinophilic infiltrate representing approximately 10% of the immature cells without morphologic atypia. Elevated plasma levels of prothrombin fragment F1 + 2 (marker of thrombin generation) (406 pM; normal range, 68–229 pM) and fibrin fragment D-dimer (4776 ng/mL; normal range, 130–250 ng/mL) were found.Since the patient had been presenting hypereosinophilia from three years with no evident cause, idiopathic hypereosinophilic syndrome (HES) was diagnosed. Steroid treatment with oral prednisone (50 mg daily) was started and the patient was discharged

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S250 asymptomatic. Eosinophil count progressively decreased till normalization as well as the coagulation markers F1 + 2 and D-dimer, and steroid was progressively tapered until 10 mg daily. The patient is currently asymptomatic. Although the introduction of ranolazine by itself could explain the good outcome of the patient, we speculate that also the reduction of eosinophil count has given an important contribution. In fact, an increased incidence of thromboembolic events has been described in patients with hypereosinophilic disorders, and several hypotheses have been proposed to link eosinophilia and thrombosis, involving endothelium damage, and activation of platelets and coagulation. Eosinophil products such as eosinophil peroxidase, eosinophil cationic protein and major basic protein can damage endothelial cells and stimulate platelet activation and aggregation. Furthermore, eosinophils store the coagulation initiator tissue factor, which is exposed upon cell activation and can trigger activation of the extrinsic pathway of blood coagulation. It is of interest that our patient showed a prothrombotic state that reverted after normalization of peripheral blood eosinophil count, as indicated by measurement of the prothrombotic markers F1 + 2 and D-dimer. Therefore, we suggest that hypereosinophilia may have contributed to aggravate ischemic heart disease.

A case report of portal vein thrombosis linked to CMV infection C. Sgroi, J. Timpanaro, P. Pignataro, M. Cavarra I Divisione di Medicina, Azienda Ospedaliera Universitaria ‘‘Policlinico-Vittorio Emanuele’’ di Catania, Catania, Italy The patient, a 54 year-old-male, has been complaining for a month of asthenia and adynamia, malaise and fever (CT max 39C) which recedes after oral administration of paracetamol. The laboratory tests, performed at home, show: ESR 29 mm, CRP 26 mg/l, GOT 58 U/l, GPT 132 U/l, LDH 774 U/l (as a cytolysis index), gammaGT 252 U/l (as a cholestasis index). The general practitioner begins an antibiotic therapy: ciprofloxacin 500 mg bid and Ceftriaxone 1 g/die im for approximately 10 days, then, because of the prolonged symptoms, he changes it with Trimetoprim 160 mg/sulfamethoxazole 800 mg bid + 250 mg Metronidazolo bid. The patient is then admitted to our Department for abdominal pain on the right side. On admission, the patient is without fever (CT 37.2C) and hemodynamically stable (PA 120/70 mmHg, HR 80 b/min). Abdominal objectivity: dull pain to abdominal deep palpation on the right side. Blood tests confirm the increase of inflammatory markers (ESR 36 mm, CRP 9.6 mg/l, ferritin 3,414 ng/ml), the cytolysis markers (GOT 73 U/l, GPT 87 U/l, LDH 785 U/l) and cholestasis indexes (gammaGT 336 U/l, alkaline phosphatase 149 U/l) and an increase of leukocytes (with a relative lymphocytosis at the beginning, that becomes absolute subsequently). We perform an abdominal ultrasound, which shows a massive thrombosis of the right branch of the portal vein and the superior mesenteric vein, confirmed by the emergency CT, which excludes the presence of focal liver lesion. Chest CT is negative and ECG is normal. We complete the laboratory tests with the research of autoantibodies (ANA, AMA, ASMA and LKM), cancer markers and hepatitis markers, EBV. All these tests are negative. Only anti-CMV is positive (IgM 75 IU/ml and IgG 4.2 IU/ml). Thrombophilia screening is also performed to exclude genetic causes (antithrombin III, protein C and protein S coagulation deficiency, factor V Leiden deficiency) and non-genetic ones (hyperhomocysteinemia, antiphospholipid antibodies).

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 During the hospitalization, the patient proceeds with the antibiotic therapy (Ceftriaxone 1 g i.m. a day) and starts treatment with LMWH (low molecular weight heparin): enoxaparin sodium 8000 IU sc bid, associated with warfarin 5 mg orally. When the INR reaches the target of 2.5, the LMWH is withdrawn. After 7 days, the patient performs a new abdominal ultrasonography; the report is that the right branch of the portal vein appears to be rehabilitated up to the first fork and the subsequently abdominal CT reports an almost complete recanalization of the right branch and its secondary branches of the intrahepatic portal vein, also with the resolution of the superior mesenteric vein thrombosis. The patient is discharged with the diagnosis of ‘‘Portal vein thrombosis likely associated with acute CMV infection’’, since any other cause could explain the thrombosis. Discussion: Portal vein thrombosis can be determined in 70% of cases by myeloproliferative disorders, genetic thrombophilia (antithrombin III, protein C and S coagulation and factor V Leiden deficiency), also in heterozygosis, or non-genetic thrombophilia’s disorders (hyperhomocysteinemia, LAC). In some cases (approximately 20%) it can be determined by a local disease (abdominal trauma, acute or chronic pancreatitis, appendicitis, cholecystitis, cirrhosis) or infectious processes of the liver. In rare cases, some viral infections could lead to systemic alterations of the hemostasis ranging from insignificant change in laboratory values to the disseminated intravascular coagulation (DIC). In vitro studies have shown that the acute CMV infection results in pro-coagulating effects, as the direct damage of endothelial cells and the state of systemic inflammation would lead to a condition of hypercoagulability. This is due to the direct activation of thrombin and to a down regulation of the physiological mechanisms of anticoagulation (in particular the inhibition of fibrinolysis). Only 11 clinical cases of acute DVT CMV-mediated have been published in literature; all the patients were immunocompetent. Three of them did not complain of any abdominal pain, but all had elevated serum transaminases. Therefore, our case report enriches the journal with a further case of acute CMV infection in immunocompetent responsible for DVT (deep vein thrombosis) and without risk factors for thrombosis. Furthermore, this case report ca help physicians focus their attention to any patient with portal vein thrombosis without any reasonable cause. The patient has completely resumed his work and lifestyle and after 6 months of follow-up he is in good health and stops the warfarin therapy.

Prognostic clinical prediction rules to identify low-risk pulmonary embolism: a systematic review and meta-analysis A. Squizzato, M.P. Donadini, L. Galli, F. Dentali, D. Aujesky, W. Ageno Research Center on Thromboembolic Disorders and Antithrombotic Therapies, Department of Clinical Medicine, University of Insubria, Varese, Italy Background: Prognostic assessment is important for the management of patients with acute pulmonary embolism (PE). A number of clinical prediction rules (CPRs) have been proposed for stratifying PE mortality risk. Objective: To assess the performance of CPRs in identifying low-risk PE. Data sources: MEDLINE and EMBASE databases were systematically searched until January 2011.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Study selection: Derivation and validation studies that assessed the performance of prognostic CPRs in predicting adverse events-risk in PE patients. Titles, abstracts, and articles were reviewed independently by 2 of the authors. Of 1,010 references in the original search, 28 relevant articles were included. Data extraction: Information on study design, characteristics of the study population, and outcome were extracted. A scoring system was used to divide studies into two quality categories. Data synthesis: Weighted mean proportion and 95% confidence intervals (CIs) of adverse events were then calculated and pooled using a fixed and a random-effects model. Statistical heterogeneity was evaluated through the use of I2 statistics. Nine CPRs were assessed in 32 cohorts, for a total of 32,052 patients. Data were prospectively collected in 22 cohorts (68.8%). Pulmonary Embolism Severity Index (PESI) and prognostic Geneva CPR were investigated in 16 and 6 cohorts, respectively. Ten (31.3%) cohorts were of high quality. Median follow-up was 30 days. In low-risk PE patients, pooled short-term mortality (within 10 days or less) was 0.8% (95% CI 0.4–1.4%, random-effects model; I2 = 49.1%), 30-day mortality was 1.72% (95% CI 1.14–2.41%, random-effects model; I2 = 83.1%), and 90-day mortality was 2.39% (95% CI 1.32–3.77%, random-effects model; I2 = 54.5%). PESI and Geneva CPR identify a substantial group of PE patients with in-hospital mortality of less than 1%. Conclusion: Prognostic CPRs efficiently identify PE patients at low risk of mortality. CPRs should be implemented in the routine care of PE patients to drive appropriate management.

S251 Results: At exhaustion, heart rate and systolic pressure were significantly higher in sedentary than in trained subjects, whereas VO2max, blood glucose and plasma lactate levels were similar in all groups. Exercise induced similar GH responses in younger sedentary and exercise-trained subjects and in older exercise-trained subjects, with mean peak levels 7.5 times higher than baseline. In contrast, in older sedentary women peak GH level was only 4.4 times higher than baseline and was significantly lower than in the other groups. Conclusion: These data suggest that in women prolonged physical training exerts protective effects against age-depended decline in GHsecretion. This study let us to hypothesize that a prolonged physical activity for many years had protective effects against age-dependent neuroendocrine changes. GH plays important anabolic actions and the defective GH activity in the years preceding menopause might play a role in the development of catabolic processes which characterized the following menopausal period. Counteraction by physical exercise of GH decline during the premenopausal age would be of great interest, because it might contribute to delay catabolism of muscle, bone and parenchymatous organs in senescence.

Thyroid involvement in al amyloidosis: ultrasound findings and cytological aspects G. Carnevale Maffe`1, L. Magnani1, L. Brunetti1, D. Padula1, A. Vailati1, G. Merlini2, G.R. Corazza1 First Department of Medicine; 2Centro per lo Studio e la Cura delle Amiloidosi Sistemiche, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy

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Endocrinology Effect of physical training on age-related reduction of GH-secretion during exercise in normally cycling women A. Araldi, F. Maccanelli, M. Maggio, V. Coiro, P. Chiodera, R. Volpi Dip. di Medicina Interna e Scienze Biomediche, Azienda OspedalieroUniversitaria di Parma, Parma, Italy Objective: To evaluate whether prolonged physical activity (25 km/ week running for 8 years) modifies GH decline. It is generally accepted that in men and also in women GH secretion declines with aging from the third decade of life. This is an important phenomenon, because with increasing age, defective somatotropic function mainly contributes to loss of bone, muscle and parenchymatous organs. Design: The GH response to maximal exercise on bicycle-ergometer was tested in younger (26–30 years) and older (42–46 years) healthy women. Each group included 2 subgroups of 10 sedentary and 10 runners, which were compared. All women were non-smokers, in good health, without clinical or laboratory evidence of hepatic, renal, heart or other organic disease. Exercise test on electrically braked cycle ergometer. The workload was increased at 3 min intervals from time 0 until exhaustion. Subjects with a low maximal capacity (as established in a preliminary test) pedale for 3–4 min against no workload at the beginning of the test, so that exercise lasted about 15 min in all individuals. Basal blood samples were collected at time -30, thirty min later (time 0) and after 5, 10, 15, 20, 30, 40, and 50 min. During exercise the subjects breathed through a low resistance one way valve connected to a PK Morgan measurement system. At the exhaustion the following non-endocrine physiological parameters (NEEP) were measured: heart rate, systolic and diastolic blood pressure, oxygen consumption (VO2), blood glucose and plasma lactate levels.

Background and Aims: AL amyloidosis is a systemic disease in which clonal plasma cells produce monoclonal light chains that deposit in tissues as amyloid fibrils, resulting in progressive dysfunction of involved organs. At least 21 types of amyloidosis are classified according to the different types of protein that form amyloid fibrils in vivo. However, AL amyloidosis is the most common form of systemic amyloidosis in western countries, with an estimated incidence of 0.8 per 100,000 person years. The diagnosis of amyloidosis requires the histological demonstration of the amyloid deposits in organ biopsies. Although involvement of the thyroid gland by amyloid is a relatively common phenomenon, clinically significant enlargement of the thyroid owing to amyloid deposition is an extremely rare occurrence. Ultrasonograph is very useful in the diagnosis of parenchymal involvement due to AL amyloidosis. The Authors analyzed the result of ultrasound scan (US scan) and fine needle aspiration biopsy (FNAB) in patients with AL amyloidosis to assess the typical findings of thyroid involvement. Patients and Methods: The Authors studied 5 patients affected by AL amyloidosis (4 males, 1 female; age 58–70 years) that showed at the scintigraphy focal accumulations of 99 Tc-aprotinin in the neck region. Urine Monoclonal components (4 BJ k, 1 BJ j) were detected in all patients, while serum immunofixation detected IgG j and IgG k in two of them. All patients were clinically evaluated and underwent a complete thyroid blood panel. Then they performed a neck sonography, an ultrasound guided fine needle aspiration biopsy and a thyroid technetium scintigraphy. The volume, morphology and sonographic patterns of the thyroid were assessed. Results: All patients were clinically silent, the thyroid activity was normal in four of them, while one demonstrated a subclinical hypothyroidism. The sonographic evaluation showed a global enlargement of the thyroid, in one case a significant asymmetry was present. Borders were rounded and blurred with a cotton wool aspect and a clearly hyperechoic pattern; the echostructure was homogeneous in

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S252 two cases, while in the other two patients showed dishomogeneity with dilated hypoechoic, single or multiple, follicles. The cytology obtained from the FNAB demonstrated the typical apple-green birefringence of Congo red stained preparates under polarized light. Thyroid scintigraphy showed a widespread low radionuclide drug captation in the contest of enlarged gland. Discussion: The typical sonographic pattern of infiltration of the thyroid gland in amyloidosis well correlates in these patients with the cytology obtained from the fine needle aspiration.

A long history of Cushing’s syndrome undiagnosed

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Results: The patient showed a immediate postoperative recovery of visual acuity (RD 9/10, LE 5–6/10) and improvement of exophtalmos. The Patient was subjected to an ablative radiomethabolic and a decreasing steroidal therapy. At a 9 months follow up the patient shows endocrinologic and ophthalmic stability. Summary: The authors present an orbitopathy case occurred during Graves’ Syndrome clinical activity stage, in which had to operate in emergency regimen to contrast an impaired visual acuity. It was realized an orbital decompression. In the immediate post-operative patient showed a visual acuity recovery of 9/10 and a clinical stability status.

A. Denegri, A. Pende, L. Ottonello, L. Mastracci, D. Ferone, F. Dallegri Dipartimento di Medicina Interna, Clinica di Medicina Interna 1, Dipartimento di Scienze Endocrinologiche e Malattie del Metabolismo, U.O. Endocrinologia, Universita` degli Studi di Genova, Italy Cushing’s syndrome is a pathological condition studied and reported in 1932 by the American surgeon Harvey Williams Cushing considered the father of neurosurgery and is the clinical picture resulting from prolonged exposure to high levels of both endogenous and exogenous glucocorticoids (most common cause). The pituitary gland produces, among others, adrenocorticotropic hormone or ACTH. This hormone acts on the adrenal cortex where it stimulates the production of glucocorticoid hormones (cortisol is the most important). The presence of Cushing’s syndrome due to adrenal adenoma in approximately 15% of cases. Other patterns of Cushing’s syndrome, such as nodular hyperplasia, are very rare. This case report describes the case of a woman with long history of hypercortisolism (10 years) due to bifocal adrenal adenoma, rare entity reported in the literature, which has also submitted complete regression of symptoms (weight loss, normal blood pressure and serum potassium) after surgery for adrenalectomy.

Emergency treatment of Graves orbitopathy G. Fini1, E. Mici1,C.M. Scannavino1, A. Leonardi2, S. Monti1, S. Amodeo1, E. Fiesoletti1, V. Pellacchia2, M.L. Carini3 1

Nesmos Department, Facolta` di Medicina e Psicologia, Universita` degli Studi di Roma; 2Maxillo Facial Surgery Department, I Facolta` di Medicina e Chirurgia Sapienza, 3Dep.Clinical Medicine, I Facolta` di Medicina e Chirurgia Sapienza, Roma, Italy Aim: The authors report an emblematic case of orbitopathy manifested during a clinical hyperactivity status of Graves’ Syndrome, treated in an emergency surgical regimen for sudden vision impairment caused by an orbital apical crowding. Materials and methods: Male, 50 years old already affected by orbitopathy, undergone total thyroidectomy for goiter. 3 months after surgery underwent a significant decline in visual acuity examination: moderate hyperemia and conjunctival chemosis, eyelid and ocular/ caruncle severe edema, moderate upper eyelid retraction and mild bilateral keratitis. Exophthalmometry: (normal value 126 mm) RE: 21 mm, LE: 21 mm. Intraocular pressure: RE14 mmHg, LE 14 mmHg. Visual acuity: RE3/10, LE 1/10. Visual field: serious deficit. Surgical treatment for orbital decompression by Van der Wals technique.

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Stimulatory effect of naloxone on plasma cortisol in humans: possible direct stimulatory action at the adrenal cortex F. Maccanelli, A. Araldi, V. Coiro, P. Chiodera, R. Volpi Dip. di Medicina Interna e Scienze Biomediche, Azienda OspedalieroUniversitaria di Parma, Parma, Italy Introduction: Naloxone stimulates pituitary-adrenal function by blocking the endogenous inhibitory opioid tone, which modulates pituitary ACTH release. This effect is mediated by the increase of CRH secretion. On the other hand, in vitro studies in animals suggest that naloxone might act directly at the adrenal level on cortisol secretion through modifications in membrane permeability to one or more ions. Aim of the study: The purpose of the study is to gain a better insight in the mechanism of naloxone, underlying the regulation of the adrenal cortisol secretion in humans in vivo. Materials and Methods: Patients (4 women and 4 men) aged 42.4 ± 5.8 years, all with hypothalamo-pituitary disconnection because of various pathologies treated with surgery (craniopharingioma, cordoma, suprasellar meningioma and pituitary macroadenoma) and a consequent panhypopituitarism, were included in the study. All patients concentrations of cortisol and ACTH were measured after the infusion of normal saline solution and after a dose of 14 mg of naloxone (4 mg in bolus and the other 10 mg by a constant 2 h i.v. infusion). Results: During saline test, circulating cortisol concentration showed a slight decline. In contrast, in all subjects, naloxone induced a significant cortisol rise. Naloxone or saline were unable to change plasma concentrations of ATCH, which were below the detection level. During tests, hepatic and renal function were not altered by both naloxone and saline administration. Discussion: Fort the first time, this study suggest that naloxone exerts a direct effect on cortisol secretion at the adrenal gland in humans in vivo, independently of its action on the hypothalamo-pituitary unit. In fact, our data show that naloxone administration increases cortisol levels in the absence of concomitant stimulation of ACTH release. Previous data have demonstrated that naloxone exerts its steroidogenetic effect through modifications in membrane permeability to one or more ions, which result in increased intracellular ion concentrations. Lastly, a non specific action of naloxone on cortisol catabolism cannot be excluded, although this possibility is less likely. References 1. Grossman A. Brain opiates and neuroendocrine function. J Clin Endocrinol Metab. 1983;12:725–46 2. Nikolarakis K, Pfeiffer A, Stalla GK, Merz A. The role of CRF in the release of ACTH by opiate agonist and antagonist in rats. Brain Res. 1987;421:373–6

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 3. Estienne MJ, Kesner JS, Barb CR, Kraeling RR, Rampacek GE. On the site of action of naloxone-stimulated cortisol secretion in gilts. Life Sci. 1988;43:161–6 4. Hockings GI, Grice JE, Walters MM, Crosbie GV, Torpy DJ, Jackson RV. A synergic adrenocorticotropin response to naloxone and vasopressin in normal humans: evidence that naloxone stimulates endogenous corticotropin-releasing hormone. Neuroendocrinology. 1995;61:198–206 5. Edwards AV, Jones CT. Adrenal responses to splanchnic nerve stimulation in conscious calves given naloxone. J Physiol. 1989;417:79–89 6. Lymangrover JR, Dokas LA, Kong A, Martin R, Saffran M. Naloxone has a direct effect on the adrenal cortex. Endocrinology. 1981;109:1132–7 7. Jezova D, Vigas M, Jurcovicova J. ACTH and corticosterone response to naloxone and morphine in normal hypophysectomized and dexamethasone treated rats. Life Sci. 1982;31:307–14

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Fig. 1 a Correlation between systolic blood pressure (PAS) and PTH levels in PHPT patients. b Correlations between systolic (filled triangles) (r 0.69, p\0.03) and diastolic (filled squares) (r -0.87, p\0.02) endstage diameter of left ventricle and PTH levels in PHPT patients

Neurofibromatosis type 1 (Von Recklingausen Disease) and bone mineral disorders Blood pressure profile in patients with primary hyperparathyroidism (PHPT) before and after surgical treatment L. Petramala, M.C. Formicuccia, L. Zinnamosca, D. Cotesta, C. Marinelli, S. Sciomer, G. Cavallaro, G. De Toma, C. Letizia University ‘‘Sapienza’’, Roma, Italy Introduction: PHPT is a disease characterized by excessive secretion of parathyroid hormone and persistent hypercalcemia. Besides the typical clinical features of PHPT, there is an increased prevalence of hypertension, atherosclerosis and endothelial dysfunction. Objective: Aim of the study was to investigate in PHPT patients the behavior of arterial blood pressure and cardiovascular damage, before and after surgical treatment. Materials and methods: We enrolled 21 consecutive patients with PHPT (3 M, 18 F; mean age 56 ± 6 years) and 20 normal subjects (NS) (4 M, 16 F; mean age 55 ± 6 years), evaluating blood pressure profile, echocardiography, carotid intima-media thickness (IMT). Results: 81% of patients with PHPT was affected by hypertension and ABPM showed the lack of normal circadian rhythm (‘‘non-dipping pattern’’), in almost 57% PHPT patients, compared with 10% of NS. PHPT patients also had a significant cardiac and vascular remodeling respect to NS, such as interventricular septum (10.7 ± 8.8 mm/m2 vs. 8.8 ± 1.2 mm/m2; p \ 0.001), systolic and diastolic end-stage diameter of left ventricle (46 ± 5.9 mm/m2 vs. 29.3 ± 1.9 mm/m2; p \ 0.001; and 30 ± 2.4 mm/m2 vs. 18.3 ± 1.9 mm/m2; p \ 0.001, respectively), mass of left ventricle (182 ± 30.4 mm/m2 vs. 125 ± 26 mm/m2; p \ 0.001), IMT (0.76 ± 0.15 mm/m2 vs. 0.57 ± 0.07 mm/m2; p \ 0.05). We showed in PHPT patients a positive correlation between serum PTH levels and SBP values (Fig. 1a), and a negative correlation between serum PTH levels and LVESD-LVDD (Fig. 1b). The evaluation 1 year after parathyroidectomy showed a decrease of number of patients affected by hypertension (81 vs. 62%, p: 0.012), and patients with the ‘‘no-dipping pattern’’ (57 vs. 42%, p: 0.003), and decrease of mean number of antihypertensive drugs (n.1.7 vs. n. 1.05, p: 0.001); moreover, 17% of patients did not take any antihypertensive drug and 48% reduces the number and dose of antihypertensive drugs. Conclusions: Surgical treatment of PHPT normalizes calcium-phosphorus metabolism, and can reduce blood pressure profile, restore circadian rhythm of blood pressure and reduce cardiovascular remodelling.

L. Petramala, L. Zinnamosca, C. Marinelli, G. Cilenti, Mc. Formicuccia, L. Colangelo, S. Giustini, S. Calvieri, C. Letizia Department of Internal Medicine and Medical Specialties of University of Rome ‘‘Sapienza’’, Roma, Italy Introduction: Neurofibromatosis type 1 (NF1), is one of the most common autosomal, multisystemic disease, involving 1:3,500 live births. The characteristic manifestations of NF1 have been well defines and consist of cafe`-au-lait spots, cutaneous, subcutaneous of flexiform neurofibromas, axilling and inguinal freckling, optic glioma, iris Lisch nodules, some specific bone deformities. Moreover, a significantly decreased bone mineral density (BMD) has been observed in adult patients and children with NF1, implicating an increase fracture risk. The bone alterations are characterized by ‘‘bone dysplasia’’, caused by abnormal bone mineralization and aberrant cell growth, involving all bone cellular elements (osteoblasts, osteoclasts, chondrocytes, fibroblasts). Aim: Evaluate the biochemical parameters of mineral metabolism and bone mineral density values in patients with neurofibromatosis type 1, compared with a group of normal subjects, homogeneous for sex and age. Materials and Methods: In the Department of Internal Medicine and Medical Specialties of University of Rome ‘‘Sapienza’’ were enrolled 70 consecutive NF1 patients and 60 normal subjects (NS). All subjects underwent to anthropometric measurements, evaluation of mineral metabolism and bone densitometry (DXA). Results: Analysis of anthropometric data showed that patients with NF1 had a lower body mass index (BMI) compared with NS (BMI 22.5 ± 4.3 vs. 24.1 ± 4.9 kg/m2, P \ 0.05). The evaluation of bone mineral metabolism showed that patients with NF1 had a significant reduction in circulating levels of 25-OH vitamin D (21.8 ± 12.3 vs. 32.9 ± 16.5 ng/mL, P \ 0.05), with a high prevalence of hypovitaminosis D (65%), lower plasma magnesium levels (1.39 ± 0.5 vs. 1.94 ± 0.3 mmol/L, P \ 0.05), ionized and total calcium, and significant increase of urinary excretion of calcium (290 ± 70.9 vs. 146.8 ± 82.8 mg/24 h, P \ 0.05). In addition, bone deformities were observed in approximately 30% of patients, with evidence of scoliosis, macrocephaly and congenital pseudoarthrosis. As regards the assessment of mineral mass by DXA, patients with NF1 had significantly reduced values of BMD at both lumbar spine (L1–L4 Z-score -0.909 ± 0.6 vs. 0.03 ± 0.3) and in femoral neck (Z-score FN -0.892, -0.297 ± 0.7 vs. ±0.2), with an high prevalence of osteopenia (44%) and osteoporosis (18%). Our patients underwent to calcium (1.200 mg/die) and

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vitamin D (800 UI/die) supplementation, with restore of bone mineral metabolism. Conclusions: Our results show that in patients with NF1 there is a systemic disease of bone, characterized by a diffuse and generalized reduction in bone mass, due, in part, by relevant hypovitaminosis D . Table Biochemical parameters in study population Total calcium (mg/dl)

Ionizedcalcium (mmol/l)

Phosphorus (mg/dl)

Magnesium (mmol/l)

NF1 (n.70)

9.01 ± 0.4

1.18 ± 0.05

3.80 ± 0.4

1.39 ± 0.4

290 ± 70.9

683.3 ± 56.5

SN (n.60)

9.8 ± 0.4

1.26 ± 0.04

3.15 ± 0.4

3.15 ± 0.4

146.8 ± 82.8

788.8 ± 45.6

NS

NS

NS

0.04 versus NS

0.05 versus NS

NS

PTH (pg/ml)

25 OH-Vit D (ng/ml)

BALP (U/I)

BJP (ng/ml) 18.1 ± 5.6

p

NF1 (n.70)

55 ± 18.3

21.8 ± 12.3

41.2 ± 15.5

SN (n.60)

32.3 ± 15.3

32.9 ± 16.5

25.6 ± 8.7

7.6 ± 1.9

p

NS

0.01 versus NS

0.05 versus NS

0.05 versus NS

Urinary calcium excretion (mg/24 ore)

Urinary Phosphorus excretion (mg/24 ore)

PTH parathyroid hormone, 25 OH-Vit D 25 hydroxyvitamin, BALP bone alkaline phosphatase

The association between Mitral Valve Prolapse and chronic autoimmune thyroiditis

Results: Capillaroscopy abnormalities were found in 20 pts. (87%) suffering from mitral valve prolapse, whilst a normal capillaroscopic pattern was present in only three pts. (13%). Capillaroscopy abnormalities were found in all the 10 pts. suffering from mitral valve prolapse and chronic autoimmune thyroiditis. The nailfold capillaroscopy showed: Avascular areas: (score 2) in 2 pts. with AMP in one pts. with FVP, score 0 in control group (p \ 0.01). Tortuosity: (score 2) in 6 pts. with AMP and 2 with FVP and score 1 in control group (p \ 0.01). Enlargement: score 2 in 5 pts. with AMP, 3 pts. with FVP, vs. 1 in control group (p \ 0.01). Microhemorragies: score 2 in 4 pts. with AMP and 3 pts. with FVP vs. 0 in control group (p \ 0.001). 10 pts. (43%), 2 with AMP and 8 with FVP showed chronic autoimmune thyroid disease; 1 pts. with Graves disease and 8 with autoimmune thyroiditis defined as the association of abnormal TSH and an increase in anti-thyroid antibodies. 1 pts. (4.3%) showed thyroid antibodies without signs of thyroid disease. 4 pts. (50%) with AMP and 3 (20%) with FVP showed Raynaud’s phenomenon (RF) versus only two subjects (10%) of control group. In our study capillary abnormalities were mainly seen in those pts. with RP. The coexistence of capillary abnormalities and RP in pts. with mitral valve prolapse and chronic autoimmune thyroiditis may indicate that RP seen in those pts. is related to not only capillary morphological changes, but also to altered microcirculatory haemodynamics. At the time of admission in the study, a serum sample was taken for immunoglobulin (IgG and IgA) anti-gliadin antibodies (AGA), IgA anti-endomysial antibodies (EmA), anti transglutaminase (tTG). 5 pts with chronic autoimmune thyroid disease were also AGA(+), EmA(+), tTG(+) and they were also affected by Celiac disease. Conclusion: Our original findings indicate that mitral valve prolapse does induce significant morphologic changes in the microcirculation and that some of these changes are strongly related to cumulative stage.

C. Pintaudi, S. Giancotti, R. Cimino, G. Muccari, V. Nestico`, M.T. Polistena, A. Costantino, M. Conte, S. Mazzuca S.O.C. Internal Medicine, Az. Osp Pugliese-Ciaccio, Catanzaro, Italy Background: Recent study reported that Mitral Valve Prolapse can be an expression of primitive and systemic disorders of the connective tissue with microcirculatory changes. Numerous authors had reported the association between Mitral Valve Prolapse and Chronic Autoimmune Thyroiditis and had characterized the microcirculatory changes as common denominator between these pathologies. Objectives: In order to evaluate a possible common denominator between these pathologies we have studied nailfold capillary abnormalities in pts. with Mitral Valve Prolapse and we tested all the pts. for chronic autoimmune thyroiditis. Patients and Methods: Our study included 23 consecutive and non selected pts. Hospitalized (from January to December 2009) in our Unit with MVP. They were divided into two groups: 8 pts. (7 F, 1 M) mean age 38.8 ± 11 years with anatomic mitral prolapse (AMP) and 15 pts. (11 F, 4 M) mean age 33.1 ± 11 with functional valve prolapse (FVP). All participants were questioned for the presence of Raynaud’s phenomenon (RF), that was defined as the presence biphasic/uniphasic color changes with paresthesias in response to cold exposure.and underwent assays for serum TSH, Ft3, Ft4, anti-Thyroglobulin antibodies (TgAb), anti-Thyroperoxidase antibodies (TPO Ab), thyroid ultrasonography, antibody and autoimmunity screening. All the subjects enrolled in the study underwent a nail fold capillaroscopy at 2nd, 3rd, 4th, and 5th finger or both hands. The results have been compared to those obtained in 20 healthy euthyroid subjects (13 F, 7 M) mean age 37.55 ± 3.63. Statistical analysis was carried out by using the v2 test.

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Adrenomyeloneuropathy: a case of acute adrenal insufficiency S. Talarico, M. Balsamo, A.M. Sapone, A. Caroleo, M. Falcone, M. Tomaiuolo U.O. di Medicina Interna Ospedale Civile San Camillo de Lellis, Manfredonia (Foggia), Italy A 49-year old man was admitted to the hospital because a sore throat, headache, nausea, malaise and myalgias. Vital signs include a temperature of 39.0C, blood pressure of 140/80 mmHg, pulse rate of 102/min, respiratory rate of 22/min, and oxygen saturation of 92% on room air. The headache began the night before. He describes it as non pulsating headache, exacerbates by moving his neck. On physical examination there was a mild nuchal rigidity and obnubilation sensorium. A neurological examination a muscle bulk in his lower extremities was diminished, tone was increased and power was reducted, shows no focal deficits. The first step in the diagnostic workup is turned out meningitidis, subarachnoid hemorrhage. A computed tomographic scan of the head obtained prior to lumbar puncture is normal. A lumbar puncture (LP) reveals clear fluid and the following results: Glucose: 120 mg/dl (nv: 40–70) Protein: 119 mg/dl (nv: 15–40) WBCs: 70/mcl Bacteria: none visualized Past medical history is significant for ‘‘Adrenomyeloneuropathy, with Y174H mutation’’ and diabetes mellitus. In the following days the patient presents fatigue, light-headedness particularly severe when he gets out of bed in the morning or rises from a seated position, and muscle weakness.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392

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Laboratory data

Variable

Referring hospital

On admission

On discharge

Cortisol 8 a.m.

lg/dl 4.5–24

7

10.5

ACTH 8 a.m. Urea nitrogen (mg/ dl)

pg/ml 9–54 \46

[1500 65.55

26.8 35.06

Creatinine (mg/dl)

0.9–1.2

1.21

0.73

Sodium (mmol/l)

146–157

137.09

143

Potassium (mmol/l)

3.7–5.5

4.76

3.54

cysteine mutations. The mutation was absent in all the relatives examined. These findings indicate that: (1) the co-presence of the RET/V804L and RET/V648I mutations may be a cause of a MEN2A disease; (2) the newly identified RET/V292M mutation is a low-penetrant cause of MEN2A disease. To depict a clinically significant genotype-phenotype correlation in MEN disease, a genetic analysis should involve all the RET candidate exons, even when the search in the ‘hot spots’ has discovered a known gene alteration.

Sunday, October 23rd 2011 Clinical Epidemiology

In this case the most likely diagnosis is acute adrenal crisis due to a minor stress (acute airway inflammation). The treatment with immediate steroid therapy (hydrocortisone 30 mg/ day, two-thirds in the morning and one-third in the evening), it was associated with ameliorating patient’s clinical picture in the following days. The presence of the following complex of findings and the history of ‘‘adrenomyeloneuropathy’’ is most consistent with adrenal insufficiency. Adrenomyeloneuropathy is a variant form of X-linked adrenoleukodystrophy both and which are rare inherited disorders of peroxisomes characterized by accumulation of very-long-chain fatty acids in the plasma, the central and peripheral nervous systems, adrenal glands and testes, which leads to dysfunction of these organs and systems.

Genetic screening for MEN-2 disease: is time to change the strategy? A. Verrienti, G. Tamburrano, M. Sponziello, M. Dima, E. Ciociola, G. Ferrara, C. Durante, S. Filetti Dipartimento di Medicina Interna e Specialita` Mediche, Universita` di Roma ‘‘Sapienza’’, Roma, Italy In the management of medullary thyroid cancer (MTC) disease, genetic screening for RET proto-oncogene mutations as well a genotype/phenotype relationship contributes to define an appropriate diagnostic and therapeutic strategy for the proband and his relatives, as described in the two families studied. In the first family the proband was a woman of 45 yr, operated for a monolateral pheochromocytoma and MTC. Two co-existent heterozygous germline RET mutations, a V804L in exon 14 and a V648I in exon 11, were detected. The mutation at codon 804 is usually associated with a less aggressive phenotype, whereas the V648I mutation has been reported only in one family with MEN2A, associated with another RET mutation. The presence of the single RET/V648I mutation (detected in three family members), was not associated with the clinical or biochemical signs of MTC. Up now, the proband’s daughter carrying only the RET/V804L mutation, is free of thyroid disease, but presented Hirschsprung’ disease at age 10. In the second family the proband discovered MTC and pheochromocytoma at age 44, carrying a novel heterozygous germline RET mutation V292M in exon 5. The mutation maps in the third cadherinlike domain of RET protein, usually not included in the RET screening procedures. Interestingly, the presence of a concomitant pheochromocytoma has never been described in association with non-

Prophylactic management of 216 splenectomized patients in a single tertiary referral centre in the years 2004–2009 A. Di Sabatino1, L. Brunetti1, V. Rosti1, G. Carnevale Maffe`1, F.P. Tinozzi2, M. Lanave4, I. Aquino5, C. Klersy4, P. Marone3, G.R. Corazza1 First Department of Medicine; 2Department of Surgery; Department of Infectious Diseases; 4Biometry and Clinical Epidemiology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia; 5Department of Preventive Medicine, ASL Pavia, Italy

1 3

Background and Aims: Splenectomy is a well-recognized risk factor for overwhelming post-splenectomy infections, as a consequence of increased susceptibility to encapsulated bacteria, with a high mortality ranging from 50 to 70%. In the last few years several strategies have been developed for prevention of infections in this group of patients, such as immunization with pneumococcal, Haemophilus influenzae type B and meningococcal vaccines, yearly influenza immunization, life-long prophylactic antibiotics and patients’ education regarding the risk and the importance of prompt recognition and treatment of infections. However, the recent literature reported a poor adherence to these recommendations. The aim of our study was to determine the adherence to guidelines in term of vaccination and patient education to vaccine prophylaxis, and the mortality rate in splenectomized patients. Patients and Methods: We retrospectively analysed data of 216 patients splenectomized at our Hospital between January 1st 2004 and December 31st 2009. The data were collected from hospital records using a standardized survey form and examined to determine demographic details, diagnosis, date and reason for splenectomy, any history of infections, type of infection (i.e. sepsis, pneumonia, meningitis), organisms and serotype, outcome (healing or death) and whether vaccinations had been given (in particular meningococcal polysaccharide vaccine, Haemophilus influenzae type B conjugated vaccine, 23-valent pneumococcal polysaccharides vaccine and the Influenza vaccine). The indications for splenectomy were classified into four groups: (1) solid tumors, (2) traumatic rupture of the spleen, (3) hematopoietic disorders, (4) other causes (including abdominal aneurisms, pancreatic cyst, amyloidosis, sarcoidosis, leishmaniosis). All analyses were done by the computer program SPSS v13.0. A p value less than 0.05 was considered statistically significant. Results: Of the 216 splenectomized patients, 126 were males and 90 were females. Patients were splenectomized in decreasing scale for: haematopoietic disorders (84/216 patients; 39%), solid tumors (62/ 216 patients; 29%), traumatic rupture of the spleen (49/216 patients; 23%) and other causes (21/216 patients; 9%). Among the 216 splenectomized patients, 146 (67%, CI: 60.9–73.8) received one or more of the four indicated vaccines. In particular, the most frequent administrated vaccine was the pneumococcal vaccine (145/216

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392

patients; 67%, CI: 60.4–73.5), followed by meningococcal vaccine (141/216 patients; 65%, CI: 58.5–71.6), Haemophilus influenzae type B vaccine (74/216 patients; 34%, CI: 27.9–41.0) and the influenza vaccine (6/216 patients; 2.8%, CI: 1.0–5.9). Patients with haematologic disorders were the most frequently vaccinated (71/84 patients; 84%), followed by patients splenectomized for trauma (33/49 patients; 67%), patients splenectomized for other causes (14/21 patients; 66.7%) and patients affected by solid tumors (28/62 patients, 45.2%). Median follow-up was 50.2 months (range 32.3–63.2). Mortality was significantly greater in the unvaccinated group than in the group who received pneumococcal vaccination (33 vs. 4%, p \ 0.0001), anti-Haemophilus influenzae vaccination (14 vs. 6%, p = 0.0019) and anti-meningococcal vaccination (29 vs. 5%, p \ 0.0001). On the contrary, no significant difference in the mortality rate was found between the groups as far anti-influenza vaccine (12 vs. 0%, p = 0.12). Conclusions: Our results show a higher adherence to anti-pneumococcal, anti-meningococcal and anti-Haemophilus influenzae vaccine prophylaxis than that reported by the current literature. This led to an increased survival rate in the vaccinated group compared to patients who did not receive vaccinations. The development and implementation of national guidelines for the optimal management of splenectomized patients are urgently required.

studies), and 5 years (3 studies), was 9.3 and 33%, respectively. The risk of major events associated with syncope in the short term (10 days, 6 trials) was 18.3% and decreases over time. Finally, the average risk of short and long term syncope recurrence is summarized in the following table:

Syncope prognosis and recurrence risk: a systematic review of the literature

Impact of pneumonia on the emergence of Clostridium difficile infection: a monocentric study

F. Dipaola1, G. Costantino2, A.M. Rusconi2, M. Solbiati2, G. Casazza3,4, F. Barbic5, F. Perego2, A. Galli6, M. Borella7, F. Casella2, L. Angaroni2, E. Scannella2, M. Orlandi2, R. Furlan4,5

G. Fabio1, M. Carrabba1, L. Mellace1, M. Zarantonello1, S. Castaldi2, M.D. Cappellini1

1

2

Medicina Interna, Sesto S.G.; Medicina Interna, O. Sacco, Milano; Statistica Medica, O. Sacco, 4Universita` di Milano; 5Medicina Interna, Seriate; 6Pronto Soccorso,Vimercate; 7Medicina d’Urgenza, Legnano, Italy

3

Background: Syncope recurrence is known to markedly worsen the quality of life of individuals who had suffered from a loss of consciousness, thus deeply affecting the final costs of a syncope work-up. Although several studies have analyzed the syncope relapse rate, there are no conclusive data on syncope recurrence risk. Aims: To assess the absolute risk of syncope recurrence after a first episode, the risk of recurrence in relation to age, etiology of syncope and defined time intervals, and the short and long term prognosis. Methods: We conducted a systematic literature search in PubMed and Embase using the following terms, both as textwords and as MeSH terms: (‘‘syncope’’ or ‘‘loss of consciousness’’ or ‘‘unconscious*’’ or ‘‘faint*’’ or ‘‘drop attack’’ or ‘‘dizziness’’ or ‘‘lipothymia’’) AND (‘‘follow up’’ or ‘‘cohort’’ or ‘‘mortality’’ or ‘‘prognosis’’ or ‘‘outcome’’ or ‘‘recurrence’’). We included all prospective studies about adult patients with a transient loss of consciousness of suspected syncopal nature absolute or in relation to the age, class and etiology. The observation time frame of the followup was at least 1 week. We focused on at least one of the following outcomes: syncope recurrence, short or long term mortality, short or long term major events. Studies on syncope etiological subclasses were also included. Two reviewers analyzed in extenso the full text of all articles selected. In case of doubt the opinion of a third reviewer was asked. Results: 41 studies published between 1982 and 2008 were included, for a total of 17884 patients. The average risk of mortality at 10 and 30 days (10 and 6 studies) was found in both cases to be 1.3%; the average risk of long-term mortality, estimated at 12 months (17

123

Time

Studies Patients Events Hetero- Risk geneity (%)

CI 95%

30 days 3–9 months

1 2

45 350

1 18

– NS**

2.2 5.2

0.3–14.2 3.3–8.2

10–15 months 7

1992

336

S*

18.3

12.0–27.1

3–5 years

502

131

–

26.1

22.1–30.5

1

Conclusions: The systematic review of the literature can be a useful tool to derive a more accurate risk of recurrence in patients with syncope. However, because syncope recurrence was non homogeneously addressed in previous studies, definitive conclusions are still laking.

1

Dip. di Medicina Interna, UO Med. Int. 1-A; 2UO Qualita`, Rischio, Accreditamento, Appropriatezza E Privacy, Universita` degli Studi di Milano & Fondaz. IRCCS ‘‘Ca’ Granda’’ Ospedale Maggiore Policlinico, Milano, Italy

Background: Treatment of pneumonia accounts for 75% of all antibiotic use worldwide, and consequently may contribute to the spread and development of Clostridium difficile infections. Clostridium difficile is one of the most important causes of healthcare acquired diarrhea and is a cause of increasing hospital morbidity and mortality, length of hospital stay and costs of hospitalization. We prospectively evaluated the prevalence of C. difficile infection (CDI) acquisition rates in patients hospitalized with pneumonia and compared all causes of inhospital mortality and length of stay among patients with and without CDI. Methods: The study was based on aggregated hospital routine data covering the period 2007 to 2010 for patients admitted to Internal Medicine Dept. of a tertiary care university hospital in Milan. Research was performed using the ICD-9-codes indicating pneumonia and CDI. In a subgroup of patients with both diagnosis of pneumonia and CDI, comorbidities and administered therapy were analysed, Results: Among all hospital admissions (n = 3560), 17.9% had a diagnosis of pneumonia (n = 637) and 3.9% received a diagnosis of CDI (n = 138). Patients who had both diagnosis of pneumonia and CDI were 35.5% of the overall CDI and 7.7% of the overall pneumonias CDI in patients hospitalized with a diagnosis other than pneumonia was 2.5%. The patients affected by both illness were older (81.8 ± 7.9 yrs) than the patients with pneumonia (75.2 ± 14.2 yrs) or CDI (75.7 ± 15.7 yrs) and had a longer hospital stay (30.2 ± 13.6 days) compared with the other two groups (pneumonia: 16.5 ± 14.5 days; CDI: 20.2 ± 14.5 days).

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 All causes of in-hospital mortality was 26.5% (n = 13/49) in the group of patients with both pneumonia and CDI, while in the group with pneumonia was 17.7% (n = 104/588) and in patients with CDI was 11.2% (n = 10/89). Conclusions: These data shown that the prevalence of C. difficile infection (CDI) in this study setting is high, even if it is in a nonoutbreak setting with a low endemic rate. The patients with both pneumonia and CDI are at increased risk for mortality and have longer lengths of stay compared to patients with only pneumonia or only CDI. It is well-known that, antibiotic therapy for pneumonia, mainly based on newer fluoroquinolones, b-lactams and macrolides, combined with high-dose or long-term use of proton pump inhibitor drugs increase the risk of CDI. Moreover, this cohort of patients with both pneumonia and CDI is older, thus affected by many comorbidities and disabilities, factors increasing the occurrence of hospitalacquired infection, and CDI as well.

Twenty-four hour blood pressure changes induced by the L’Aquila earthquake P. Giorgini, R. Striuli, M. Petrarca, L. Petrazzi, E. Biferi, S. Ciarla, P. Pasqualetti, C. Ferri Division and School of Internal Medicine, University of L’Aquila, San Salvatore Hospital, L’Aquila, Italy Introduction: Although an earthquake is expected to cause marked changes in blood pressure, very poor data are available on either office or 24 h ambulatory blood pressure monitoring (ABPM). Aim: To retrospectively evaluate the effects of the 2009 L’Aquila earthquake on 24 h ABPM. Methods: We recorded all patients who had an ABPM (Spacelabs 90207)—performed in our Outpatient Unit—both before and after the earthquake. Results: We identified 47 patients (25 f, age 52 ± 14 years). Patients were divided into 3 groups according to antihypertensive therapy after the earthquake: 1. unchanged therapy (UT) (n = 24, 15 f, mean age 54 ± 13 years), 2. increased therapy (IT) (n = 17, 8 f, mean age 53 ± 13 years) and 3. reduced therapy (RT) (n = 6, 2 f, mean age 42 ± 13 years). In the UT group, 24 h (125.6 ± 10.7 vs. 132.1 ± 13.5, p = 0.004), day-time (130.3 ± 11.6 vs. 136.4 ± 13.5, p = 0.01) and night-time systolic BP (SBP) (118.3 ± 11.9 vs. 123.3 ± 14.3, p = 0.02) as well as 24 h (76.5 ± 7.7 vs. 80.6 ± 9.8, p = 0.005), day-time (80.7 ± 9.2 vs. 84.5 ± 10.1, p = 0.01) and night-time diastolic BP (DBP) (69.4 ± 6.6 vs. 73.8 ± 9.7, p = 0.009) increased after the earthquake. In the IT group and in the RT group blood pressure levels remained unchanged. Data collected by telephone interviews showed in the UT group: housing discomfort (45.8%), feeling of stress (66.7%), decreased quality of life (54%), reduction in daily physical activity (37.5%), problem with daily diet (29.2%), and working problems (8.3%). In both the IT and the RT groups interviews showed similar data. Conclusions: Marked increments in 24 h, day-time and night-time blood pressure levels occurred in the long term after an earthquake, particularly in the UT group, in the presence of evident earthquakerelated socio-economic problems in all of the three groups. In the IT group, appropriate modifications of the antihypertensive therapy were probably responsible for the lack in BP increments. Only 6 patients had a reduction in their antihypertensive therapy and any conclusion

S257 about the unexpected BP behaviour observed in the RT groups would sound as arbitrary.

Prevalence of hereditary haemorrhagic telangiectasia in Apulia population: a population-based study using administrative and clinical informative sources G.M. Lenato1, P. Suppressa1, P. Lastella1, A. Papagni2, B. Contegiacomo2, F. Resta1, E. Attolini2, G. Annicchiarico3, G. Logroscino4, C. Sabba`1 1 Geriatric Unit and Sovra-Unit Center of Rare Diseases, Policlinico, University of Bari; 2ARES-Puglia; 3Apulia Center of Regional Coordination for Rare Diseases; 4Department of Neurologic and Psychiatric Sciences- University of Bari, Bari, Italy

Background: Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominantly-inherited vascular disease, with multi-organ involvement and incomplete penetrance. HHT is characterized by a strong clinical heterogeneity, ranging from spontaneous frequent epistaxis to many complications secondary to visceral arterio-venous malformations (brain abscess, stroke, dyspnea, chronic GI bleeding, etc.). The prevalence of HHT is around 1–2:10,000, thereby classifying HHT as a ‘‘rare disease’’ according to current EU guidelines (prevalence \ 5:10,000). However, as for other rare disorders, a reliable estimation of HHT prevalence in many countries is currently not available due to a number of factors, including insufficient patient ascertainment, mainly based on recruitment by referral centers, lack of information regarding disease evolution over time, and enrollment of inappropriate cases due to non-accurate diagnosis. Furthermore, HHT epidemiological studies have been considerably hampered by the heterogeneity of clinical features and variability of age onset. In particular, no epidemiological studies currently exist assessing the prevalence of HHT in Italian regions. Conclusive epidemiological studies for rare disorders, such as HHT, require multiple information sources from both administrative data and clinically specialized centers. Aims: To estimate the prevalence of HHT in the Italian Apulia Region using both administrative data sources and clinical charts of patient recruited by the Bari HHT Center which is one of two Italian HHT referral Centers specializing in diagnosis, research and treatment of HHT patients recognized by the International HHT community. Methods: Three informative sources were employed in this study, spanning over 9 years (2001–2009): (a) administrative collection of hospital discharge records (HDR) from the Regional Department of Health Informative System. The HDR database was screened for the HHT ICD-10 code (448.0) and all HDRs containing a diagnosis of HHT were obtained: HDRs from both Apulian hospitals and Italian non-Apulian hospitals were targeted. Patients in Apulia were identified by personal administrative-sanitary codes, after editing to correct for false duplications due to administrative errors. (b) the administrative database of Apulian patients who benefit from legal fiscal advantages for medical treatment of rare diseases (DM 279/2001). Screening of this database was performed with the RG0100 code, corresponding to HHT (c) patients’ clinical charts from our HHT Center of Excellence for the period 2001–2009. Patients with an Apulian residence and definite HHT diagnosis were admitted into the study; definite diagnosis was based on international Curacao clinical criteria (presence of 3 or 4 criteria [Shovlin et al., Am J Med Genet 2000]) or on the results of genetic testing if the familial mutation was previously identified [Lenato et al., Hum Mutat 2006], independent of clinical features. Patients detected by the three informative sources were then cross-checked to estimate prevalence rate. Results: A total of 178 patients were found by the first administrative source, and 60 patients by the second source. Cross-checking with

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S258 data contained in the patient database of the Bari HHT Center corrected for case misclassification and permitted the identification of 199 patients living in Apulia over 2001–2009 definitely affected with HHT. A prevalence rate of 0.4 per 10,000 was found with a maximum in the Bari area and lower rates for Foggia and Lecce, suggesting a gradient effect. The overall prevalence found is 2.5- to 5.0-fold lower than expected (1–2:10,000). Conclusion: The multi-source approach permitted us to identify numerous patients who would have been missed with an epidemiological study based only on one informative source. However, the lower than expected prevalence rate and the apparent gradient effect in areas distant from the Bari HHT Center suggest that many HHT patients are still underdiagnosed, which is consistent with current data. Further efforts will be targeted to improve awareness of HHT in general practitioners and potentially affected families to reduce the number of underdiagnosed HHT cases and life-threatening complications. The organization of the Apulian Registry of Rare Diseases is expected to contribute significantly to identification of still undiagnosed HHT patients.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 comparison with the 259 case subjects for the analysis of INAIL data bank. Results are shown in the table:

Cases

Controls

P

N. workers

259

265

M/F

253/6 (97%)

257/8 (96%)

n.s.

Age (M ± SD)

38.9 ± 11.1

37.8 ± 11.1

n.s.

BMI (M ± SD)

26.6 ± 4.1

25.2 ± 3.6

0.0001

N. injured workers

107/259 (41.1%)

94/265 (35.4%)

0.05

M/F of injured workers

107/0

94/0

n.s.

N. total accidents

320

237

–

N. accidents/worker

2.9 ± 3.0

2.5 ± 2.2

n.s.

Absence from work (days)

30.2 + 40.7

23.4 + 41.7

0.001

Alcohol consumption and lifestyles in working class heroes V.O. Palmieri1, D. Lomazzo1, M.T. Salerno1, R. Attimonelli2, Di Leone3, D. Santovito1, G. Palasciano1 1 Clinica Medica ‘‘A. Murri’’, University of Bari, Italy; 2INAIL, Bari, Italy; 3ASL Bari, Italy

Background: WHO estimates that 10–30% of industrial accidents may be due to alcohol consumption and a recent Italian law establishes guidelines for the prevention of these accidents. In order to get insights into alcohol consumption styles and other lifestyles, we performed an extensive survey among almost 3,000 people of different working class sectors. This work is the result of the collaboration between University of Bari, INAIL Puglia, Regione Puglia and the Policlinico General Hospital in Bari. Methods and Subjects: The health survey questionnaire (Wallace 1987) was used in combination with CAGE (Cut, Annoying, Guilty, Eye-opener) questionnaire (2,530 cases, M/F: 4, 8; range 16–69 yrs) or the Alcohol Use Disorders Identification Test (AUDIT) (Fiellin 2000) (593 cases; M/F: 2, 1; range 17–69 yrs). Both questionnaires are widely used as screening tools for the diagnosis of risk for alcohol dependence and allow the classification of interviewed subjects into four main groups: abstinent, moderate consumers, risk consumers, alcoholics. AUDIT is made up of ten questions and is regarded as a more sensitive instrument for the diagnosis of alcoholism; CAGE encloses only four questions and therefore is used more frequently as a screening tool in routine context. Data on the alcoholic subjects identified by both questionnaires have been further crossed with INAIL data bank on the frequency and typology of working accidents. Results: Distribution of BMI was: 25–29.9: 36,7%; C30:11,4%. Physical activity is done by 48% of males and only 36% of females; smoking: 47% of males, 38% of females; fruit consumption:[95% in both sex; alcohol consumption: 76% of males, 47% of females; depression feeling: 2% of males, 4% of females. A total of 259 workers resulted at risk or positive for alcoholism. In detail, in the CAGE group, 2% of people (only males) gave 3 or 4 positive answers (hazardous or risk drinking, high risk of alcoholism) and 7.5% 2 positive answers (suspect of risk drinking). In the AUDIT group, 3.5% of people (only males) gave [6 positive answers (hazardous or risk drinking). 265 abstinent workers, matched for sex and age, were consecutively selected as a control group for the

123

Conclusion: alcohol, overweight and smoking are primary health problems in working class and claim for intensive preventive actions; alcohol consumption is directly related to the risk and to the severity of work accidents.

When politics meets health and science: the approach of Apulia region to care for rare disease patients P. Suppressa1,P. Lastella1, Gm. Lenato1, F. Resta1, P. Facchin2, E. Attolini3, F. Bux3, G. Annicchiarico4, T. Fiore5, N. Vendola5, C. Sabba`1 1

Geriatric Unit and Sovra-Unit Center of Rare Diseases, Policlinico, University of Bari; 2Rare Diseases Center of Venetian Region; 3 Apulia Regional Agency of Health; 4Rare Diseases Center of Apulia Region; 5Apulia Regional Government, Bari, Italy Background: Diseases with prevalence not exceeding 5:10,000 are defined as ‘‘rare’’ in EU. Current estimates report at least 7,000 different rare diseases. Although a single rare disease affects only a small number of people, it usually leads the patients and their families to withstand to considerable health care load and marked discomfort. Notably, when considering globally all rare diseases, these patients represent *10% of all subjects affected with any type of pathological condition, thus accounting for a heavy clinical and social burden (exemplified by the assumption that ‘‘Rare diseases are rare, but rare disease patients are numerous’’). Rare diseases are often characterized by a considerable clinical heterogeneity and affected patients require highly specialized and often personalized diagnostic and therapeutical approaches which are rarely compatible with the Health Systems in most countries. Pharmaceutical Companies demonstrate a lack of interest in launching low-financial-return drug research for rare disease patients, thereby determining insufficient availability of therapeutical options for these patients, often referred to as ‘‘orphan patients’’. As a final but not irrelevant issue, there is much difficulty to receive a proper diagnosis within a sustainable time limit for these patients, many of whom have a diagnostic lag ranging from few months to several years, often implying costly and uncomfortable travelling outside their home region (or home country). The complex approach to diagnosis and cure of rare diseases actually represents a true challenge for public health services, both in Italy and in other countries: the capacity to meet the health demands of these patients is

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 an essential issue for a Health Care System whose aim is to reach quality levels of excellence. In the last decade, the concern for rare diseases has gained increasing attention at both the European and Italian level, resulting in the adoption by the Italian government of the fundamental law (DM 279/01) dealing with treatment of rare disease patients, in collaboration with Regional Health Systems. In this scenario, every Region has to establish its own regional policy, in partnership with an Inter-regional collaborative network. Objective: To summarize the initiatives (under Deliberazione di Giunta Regionale, DGR) undertaken by the Apulia Regional agency in order to comply with the aims of the National Law and coordinate the Regional Health Care Service with similar corresponding initiatives of other Italian Regions. Results: The Apulia Region has formulated the following Deliberations to reach the aforementioned aims: (a) DGR of December 23, 2003, n. 2238; (b) DGR of April 5, 2006, n. 464; (c) DGR of February 19, 2008, n. 171; (d) DGR of March 25, 2008, n. 393; (e) DGR of December 15, 2009, n.2485; (f) DGR of August 4, 2010, n. 1833; (g) DGR of October 4, 201, n. 2,152. The following activities have been initiated: (1) A Regional Coordination Center for Rare Diseases, in the Agenzia Regionale della Sanita` (ARES-Puglia); (2) A SovraUnit Center for Health Care of Rare Diseases associated with the Geriatric Unit in the Bari University Hospital, (3) An ongoing program is the Regional Registry of Rare Diseases, which has required the recruitment of various specialists (Internal Medicine, Medical Genetics, Biologists, administrative collaborators by the Sovra-Unit Center; Paediatrics, Epidemiology experts, Pharmacists by the Regional Coordination). The Registry of Rare Diseases will be linked to the Registry of other Regions already included (Veneto, FriuliVenezia-Giulia, Trento and Bolzano, Liguria, Emilia-Romagna, Campania, Puglia), by means of an institutional agreement with the Coordination for Rare Diseases of the Veneto Region, which is the national leader of this project; (4) An ongoing project is to establish Inter-Regional Referral Centers with proved expertise in specific Rare Diseases, to be identified as Centers of Excellence located within in the Regional territory; (5) An ongoing evaluation of Associations of patients of the Apulia Region affected with a rare disease. Conclusions: The activities described above will permit the optimization of health care services for the Apulia rare disease patients, in order to reduce diagnostic lags and to valorize the contribution of the Apulia Excellence Centers, thus reducing referral to outside Region Centers, with a subsequent resource rationalization. A better resource allocation will ultimately bring about an improved health care services for patients and a consequent financial saving for the Regional budget.

Approach to the human error in medicine: picture of a medicine department A. Ubiali1, F. Perego1, G. Costantino1, E. Scannella1, L. Zocchia1, P. Duca2, M. Cortellaro1 1 Department of Internal Medicine, ‘‘Luigi Sacco’’ Hospital, University of Milan, Milan, Italy; 2Medical Statistics and Biometry Unit, Clinical Science Department, ‘‘Luigi Sacco’’ Hospital, Milan University, Milan, Italy

Background: Medical errors (failure of a planned action to be completed as intended) represent a serious public health problem and pose a threat to patient safety. It is estimated that at least 44.000 people die in hospitals each year as a results of medical errors that could have been prevented. All patients are potentially vulnerable,

S259 therefore medical errors are costly from a human, economic, and social viewpoint. Currently two approaches to the problem of human fallibility exist. The person approach focuses on the errors of individuals, blaming them for forgetfulness, inattention, or moral weakness. The system approach concentrates on the conditions under which individuals work and tries to build defenses to avert errors or mitigate their effects. In Italy, though, clear data about the general approach of healthcare workers to errors and data about incident reporting systems are lacking. Objective: To determine the current perception of errors in medicine and evaluating the doctors’ and nurses’ attitudes towards handling medical errors made by healthcare workers in medicine department. Methods: To investigate knowledge and beliefs about errors in medicine, from December 2010 to May 2011 we administered anonymous questionnaires to physicians, nurses and resident physicians from the department of medicine (Medicine II, Medicine III, Rheumatology, Pulmonology, Endocrinology) of the ‘‘Luigi Sacco’’ Hospital in Milan. During a 2 h training period, personnel was then instructed to fill in incident report forms when errors happened. The reports were collected in anonymous form and included information on date, time and type of event, on perceived severity of the error and its outcomes, on main causes and factors that could reduce the outcomes’ severity. Results: 80 people out of 114 (70.0%) participated to the project (35 physicians and 18 resident physicians, 61 nurses) and 83 report sheets were collected during 6 months (total number of patients admitted in the department = 965): 62 (74.7%) by physicians and resident physicians, 15 (18.1%) by nurses; in 6 cases (7.2%) reporters did not declare their status. 34 physicians and resident physicians compiled questionnaires (64.1% of Phys and res phys) versus 46 nurses (75.4% of nurses). 17 (21.5%), 12 (15.0%) and 9 (11.2%) of the participants knew the 3 correct definitions of adverse event, near miss and sentinel event respectively. For 19 (23.7%) it was considered unacceptable committing errors and for 14 (17.5%) it was considered acceptable that the patient could be harmed because of errors. 75 (93.7%) admitted to have made mistakes at work and 78 (97.5%) expected positive outcomes from a system of errors reporting. Of the 83 reports on errors 39 (47.0%) were classified as near miss, 32 (38.5%) as adverse events, 12 (14.5%) were not classified, no sentinel events were reported. 60 (72.3%) of the events had a minor outcome, 12 (14.0%) resulted in moderate injuries, 13 (15.7%) were not classified. 52 (62.7%) were reported within 24 h from the event. Individual factors were considered as main causes of the event in 66 cases (79.5%). Organizational factors were indicated in 25 cases (30.1%), structural factors in 4 cases (4.8%) and patient related factors were reported in 2 (2.4%) cases. Among the elements that were mostly believed to reduce outcomes’ severity were early detection (n = 39, 47.0%) and luck (n = 22, 26.5%), minor factors were good planning (n = 2, 2.4%) and good assistance (n = 5, 6.0%). Conclusions: The poor performance in defining ‘‘adverse event’’, ‘‘near miss’’ and ‘‘sentinel event’’ suggests a poor awareness of errors in medicine among healthcare workers. Although almost all the people admitted to commit errors at work, only a few of them thinks doing mistakes is acceptable. The report sheets show also that healthcare workers are focused on individual (self) guilting approach rather than considering system and organizational factors. The positive attitude towards the outcomes expected from a system of errors reporting coming out from almost all the questionnaires suggests chances for changing and improving the current condition.

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Clinical Pharmacology Penicillin-resistance: a new pandemiae; small boluses for time dependent antibiotic: a revolutionary therapeutic ‘‘tool’’ M.R. Pullara, D. Zenoni, F. Carrara Divisione di Medicina Generale Ospedale di Alzano Lombardo (BG), Italy The antibiotic resistance is a worrisome developing problem of our recent medical practice. The long term antibiotic use and the lack of new antibiotic in the last years cause difficulties in the treatment of the infections. Otherwise our patients are always more older and their infections, particularly pulmonary diseases, may be deadly. We must develop new strategies to encounter this problem and the solution has to be without any increase of expenses. Antibiotic are divided in different classes, but they essentially work in two different ways: concentration and time dependent. In 2009 FADOI developed a research for a better antibiotic use, in 2010 SIMI acquired this results which consist in an i. v. continuous infusion of time dependent antibiotic. We work in a Medical Unity of peripheral Hospital where infections and consequentially antibiotic resistance could be one of the bigger problems, indeed budget and resources are limited. Starting from FADOI/SIMI guidelines we developed the following proposal, result of a multidepartment cooperation (microbiologist, pharmacist, nurses and internal doctor), it’s a ‘‘tool’’ easily applicable and without extra cost. Our items are the following: • •

The sooner therapy starts the better is for the patient’s survival. The most appropriate therapy possible: identify every time is possible the responsible microbe.

(We included in our pattern of emergency laboratory analysis antipneumocco and antilegionella antibodies urinary tests, so as mycoplasma sample). • • •

Stopping therapies at the right moment, so avoiding selection of resistant microbes. Not using antibiotic associations when not needed. Accurate selection of antibiotic used considering previous 2-week therapies.

The topic of our work is ‘‘how to use time dependent antibiotic’’; pharmaceutical parameters to be considered are: • •

M.I.C. (minim inhibiting concentration). Pharmacodynamics and pharmacokinetic.

Time dependent antibiotics (betalactamics (penicillin, cephalosporin, and monobactamic), glucopeptides, macrolides, and oxazolidones) need to have a concentration higher than MIC in infected organs for a long time, it means their efficacy depend on the duration of the maintained M.I.C. The topic therapeutically goal is reaching and maintaining the correct ‘‘steady state’’, differently from FADOI/SIMI proposal of continuous i.v. infusion we reach the steady state with a multiple somministrations. The kinetic pharmaceutical method consider many factors determining the correct doses, the most important is T ‘ which defines the elapsing time between two drug somministrations; when T ‘ is superior to 24 h an attack dose is needed to gain a quick ‘‘steady state’’, this is a load dose (LD) which allows the drug to reach the needed concentration, is bigger than a maintenance dose (MD), the subsequent dose. Continuous infusion without a load doesn’t reach the M.I.C.; nevertheless many drugs in 24 h dilution lose their pharmaceutical stability.

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Everything considering we elaborated another modality of somministration, quite revolutionary, for time dependent antibiotic. We chose ceftriaxone because of his expired license is a low cost drug, still efficient with a wide spectrum of actions. The ‘‘new way’’ we are experiencing provide an i.v. load bolus followed from four small maintenance boluses during 24 h, to mimic the continuous infusion; based on ceftriaxone kinetic four is the minimum numbers of doses allowed for ‘‘small boluses’’. Our pharmacist prepared two dosages kit: • •

Small dose (for kidney failure) 1 g LD, and 250 mg MD. Normal dose: 2 g LD, 500 mg MD.

They are diluted in saline solution, the LD in 50 cc bags, and the MD in syringe; the solution has a stability of 20 days. Like standard therapy we propose 7 days. The ward nurses, in basis of their habitual activities, decided the correct moment of somministration: 5, 11, 18, 23 o’clock. In this last month we are applying this protocol, it’s well tolerated from the patients, doesn’t interfere with the clinical activities, doesn’t compromise patient’s medical examinations and doesn’t increase ward expenses.

Safety of Anakinra in Familial Mediterranean Fever and Renal Failure E. Verrecchia, M. La Regina, A. Marinaro, C. Fonnesu, M. Giovinale, R. Landolfi, R. Manna Periodic Fever Research Center, Internal Medicine Department, Catholic University of Sacred Heart, Rome, Italy Introduction: Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent episodes of fever and inflammation, with a potential long-term complication of renal failure due to AA amyloidosis. The main treatment for FMF is colchicine, which acts preventing flogistic attacks in at least 90% of cases. However, approximately 10% of patients are reported to be resistant or non-responsive to colchicine and in these cases there is no consensus as to which second line agents should be used. Since IL-1beta involvement in FMF etiology, anti IL-1 biological drugs have been successful used. Materials and Methods: We described a 63-year-old FMF patient (M694V homozygous), with diabetic nephropathy (creatininemia, 2.6 mg/dl), in treatment with colchicine 2 mg/day, insulin, low-doses steroids for gout attacks. In 2008, he presented chronic diarrhoea, thought an obliged colchicine side effect. In August 2009, diarrhoea worsened (10 discharges/day) ascribed to an alimentary toxinfection. The patient was treated with gut antibiotics without benefit. In September 2009 he complained headache, vertigo, dyspnoea, asthenia and a severe weakness until a sudden fall. Blood samples showed myoglobin 455 ng/ml (nl \ 72) creatine-kinase (CK) 305 UI/l (nl 30–170). A search for amyloid resulted negative. Therefore colchicine reduction, proportionally to creatinine-clearance, resulted in a resolution of clinical picture of colchicine toxicity and biochemical features of myalgias, but recrudescence of flogistic flares of FMF. Thus, with a correction proportional to creatinine levels, the patient started a treatment with Anakinra. 100 mg every 2 days, with a good control of flogistic flares. A follow up of 3 months confirmed wellbeing and no further evolution of renal failure. Conclusions: Colchicine is effective in preventing FMF attacks but is burdened by adverse effects such as diarrhoea and myalgias. In our patient, renal failure contributed to enhanced colchicines side effects, since it has a narrow benefit-to-toxicity margin. In this circumstance, the colchicine reduction proportionally to creatinine-clearance is

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 needed. This case confirm the safety and effectiveness of Anakinra in preventing FMF attack even in patients with renal failure.

Gastroenterology and Hepatology

S261 (p \ 0.05). We showed that liver steatosis was significantly associated with increased central fat. Using DXA, we quantified the regional distribution of adipose tissue and found the expected association between central fat and different degree of NAFLD. We also confirmed the negative correlation between adiponectin and insulin resistance.

Relationship between non-alcoholic fatty liver disease, central fat mass and adinopectin in overweight patients L. Abenavoli1, P.H. Guzzi1, L. Di Renzo2, M. Cannataro1, F. Luzza1, A. De Lorenzo2 1

Department of Experimental and Clinical Medicine, University ‘‘Magna Græcia’’, Catanzaro; 2Department of Neuroscience, Division of Human Nutrition, University ‘‘Tor Vergata’’, Rome, Italy

Survey on alcohol consumption in a gastroenterology outpatient center of southern Italy L. Abenavoli1, P.H. Guzzi1, V. Punzo1, T. Larussa1, I. Nazionale1, E. Suraci1, M. Imeneo1, M. Cannataro1, E. Vanni2, V. Patussi2, G. Addolorato3, F. Luzza1 1

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in general population. Ultrasound (US) is the least expensive modality for detecting changes associated with NAFLD. Pre-obesity and obesity are common conditions in patients with NAFLD, and body composition (BC) assessment is indispensable to evaluate nutritional status. A more valid method for measuring BC is dual-energy X-ray absorptiometry (DXA). Recently adiponectin has been linked to improved hepatic insulin sensitivity. Our aim is to evaluate the relationship between central fat mass evaluated by DXA, US degree of NAFLD and the serum concentration levels of adiponectin. In order to show the relation between DXA parameters and the liver steatosis stage, we displayed graphically the evolution of these features among classes and we assessed the statistical significance of clinical and laboratory features. All study variables were treated as continuous variables. Summary outcome measures were reported as mean ± standard deviation. Statistical differences of laboratory and clinical variables between the four groups were evaluated by the ANOVA test. A p-value of 0.05 was considered statistically significant. The study was carried out in 31 patients, referred to our Department for a BMI greater than 25, they were recruited from January to July 2010. Of 31 patients studied, 13 were male (41.9%). In height patients (25.8%) steatosis was absent, in nine (29%) was mild, in six (19.4%) was moderate and in height (25.8%) was severe. Among these, four patients presented a value of ALT greater than the normality range, in particular one was without US steatosis, two were with mild and one was with severe US steatosis. Twenty-five patients (80.64%) showed a BMI value greater than 25 kg/m2, respectively five without, six with mild, six with moderate and eight with severe steatosis. According to waist circumference values, 16 patients (seven male) were affected by central obesity. DXA analysis showed a distribution of bone mineral content (BMC-g) and bone mineral density (BMD-g/cm2) values were similar in all patients, and not show a significant difference in the four classes of US liver steatosis. Of all DXA parameters analyzed, those that present a statistical significant difference among the four degree of US liver steatosis (p \ 0.05) were: abdominal fat (AF, %), mean value 42.6 ± 11.9 (p = 0.045); abdominal tissue mass (ATM: fat plus lean mass, kg), (mean value 7 ± 2.5, p = 0.047); abdominal fat mass (AFM, kg), (mean value 3.9 ± 1, p = 0.009). Considering distribution of L2–L5 fat tissue (kg), (mean value 5.2 ± 1.2), we observed that was higher but no significant, in patients with moderate and severe steatosis. Fasting glucose (p \ 0.95) and fasting insulin levels (p \ 0.005), showed a significant difference among the degrees of US liver steatosis. Besides the assessment of HOMA-IR index reported an increase among classes (p \ 0.05). Finally of adiponectin (mean value 7.78 lg/mL), was significant lowering compared to liver steatosis progression

Department of Experimental and Clinical Medicine, University ‘‘Magna Græcia’’, Catanzaro; 2Alcohol Center, Careggi Hospital, University of Firenze, Firenze; 3Institute of Internal Medicine, Catholic University, Rome, Italy Italy ranks first among the European countries in terms of wine production and tenth for annual pro-capita alcohol consumption. According to several national statistic surveys, there are noteworthy regional differences and in particular between northern and southern regions. Few studies have analysed the alcohol consumption in different social contexts in order to better understand the relationship between environmental, cultural, and personal variables. Some factors are definitively linked to a problem drinking behaviour; including gender, age, and culture. Aim of this study is to investigate alcohol consumption and drinking habits by a self-made questionnaire, in a cohort of patients afferent to the gastroenterology outpatient center of Tinchi Hospital, MT (catchment area population: 50,000 people), Basilicata, Italy. In total 680 non consecutive patients, 321 (47.2%) male, were recruited in this survey from December 2009 to June 2010. Median age of our cohort was 52.17 (±17.34) years. Patients were included in the following disease categories: 198 (29%) reflux disease, 170 (25%) gastritis, 59 (8.7%) gastric and/or duodenal ulcer, 28 (4%) haemorrhoids, 23 (3.4%) chronic liver disease, 14 (2.1%) liver cirrhosis, and 189 (27.8%) miscellaneous (i.e.: functional gastrointestinal disorders, dolicocolon, diverticular disease). In this cohort, 241 (35.44%) were abstinent, 255 (37.50%) occasional drinkers, and 184 (27.06%) daily drinkers. In drinkers, the prevalent alcoholic beverage was wine in 470 (69.12%), beer in 262 (38.53%), liquor in 102 (14.85%). Daily drinking was found to be more common in males (184) than in females (128) (p \ 0.05). In particular, in male patients, age, low social level, and unhappiness were slightly (p = 0.1) associated with alcohol intake. Smoking (p \ 0.05) and lower physical (p \ 0.05), intellectual (p \ 0.05), social (p \ 0.05), and cultural activities (p \ 0.05) were associated with alcohol consumption. Furthermore, drinking profile was associated (p \ 0.05) with upper gastrointestinal diseases cluster (i.e.: reflux disease, gastritis, gastric or duodenal ulcer). In Italy, the daily consumption of alcohol by each individual is decreasing, while the total number of alcohol users is increasing. However, young people are characterized both by the increase in the number of alcohol users and by a high, and increasing, amount of ethanol consumed daily. Our data are in agreement with the limited number of epidemiological studies carried out on Italian populations. In according to a Mediterranean life-style, alcohol intake was common in a gastroenterology cohort of patients. We found that daily alcohol consumption is more common in males than in females. Furthermore, data indicate that social, demographic, and cultural factors may affect alcohol intake.

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S262 Prevalence and correlates of upper gastrointestinal diseases in patients with advanced heart failure awaiting heart transplant F. Agrusta, D. Pinto, C. Caianiello, I. Mattucci, U. Malgeri, R. Andini, A. Senese, I. De Rosa, R. Utili, E. Durante-Mangoni Cattedra di Medicina Interna,II Universita` di Napoli, AO Monaldi, Napoli, Italy Background: Upper gastrointestinal (UGI) disorders, including peptic ulcer, gastritis and esophagitis, are a common complication of chronic heart failure. In this setting, possible risk factors for UGI disease include antiplatelet or oral anticoagulant use, venous congestion and bowel hypoperfusion. There are little data, however, regarding prevalence and correlates of UGI disorders in patients with advanced or end-stage heart failure. Accordingly, in this study we evaluated a prospective cohort of patients with end-stage cardiomyopathy, screened for cardiac transplantation, in order to: (1) evaluate the prevalence of UGI endoscopic and histological findings; (2) analyse the potential role of concomitant treatments in UGI disorders; (3) assess the safety of UGI endoscopy in this setting. Patients and Methods: Included in this study were 134 consecutive patients with chronic, advanced congestive heart failure, admitted to our centre from January 2008 to April 2011. All patients underwent a complete evaluation for possible cardiac transplant, including history and physical examination. Variables considered in this analysis were lifestyle (smoking history, alcohol consumption), heart failure staging (NT-pro-BNP, ejection fraction, cardiac index), cardiovascular risk factors, concomitant medications. Patients also underwent esophago-gastro-duodenoscopy (EGD), with mucosal biopsies as needed. Data are presented as medians and 5th–95th percentile range. Results: Patient median age was 53 years (range 32–66), most were males (78%). Etiology of cardiomyopathy was non-ischemic in 73 patients (54%); the median ejection fraction was 25% (range 15–35); 64 patients were in NYHA class II (48%), 56 patients in NYHA class III (42%), 8 patients in NYHA class IV (6%), 6 patients in NYHA class I (4%); median NT-pro-BNP serum levels were 2184 pg/ml (range 262–11,132) whilst the median cardiac index was 2,1 ml/kg/ min (range 1.5–3.1). Eleven percent of patients complained of UGI symptoms on admission (dyspepsia, epigastrial burning or pain). The prevalence of the major endoscopic findings was as follows: antral gastritis, 77 cases (63%); cardias incontinence, 60 cases (49%); hiatal hernia, 24 cases (20%); esophagitis, 16 cases (13%), with a Los Angeles class A appearance in 44% of them and gastroesophageal mucosal prolapse in 1 case; duodenitis, 13 cases (11%); biliary reflux, 13 cases (11%, without gallbladder disease in 85%); peptic ulcer, 5 cases (4%, 2 gastric and 2 duodenal). One hundred and three patients (85%) also underwent mucosal biopsies. In these patients, histological findings were as follows: atrophic gastritis, 24 cases (23%), dysplasia, 8 cases (7%), intestinal metaplasia, 5 cases (5%), erosion, 12 patients (11%); inflammation, 11 cases (10%). The severity of gastric inflammation was mild in 53% cases and moderate in 9%. Inflammatory changes were deemed to be acute/active in 18%, chronic in 39% and both acute and chronic in 5% of patients. The rate of H. pylori infection was 9.7%. Ninety-seven patients (81%) were on proton pump inhibitor (PPI) or H2-receptors antagonist (H2A) therapy. However, the prevalence of EGD UGI peptic lesions was 74% in PPI/H2A treated patients compared to 65% in untreated patients (p = 0.54). Seventy patients (58.5%) were on oral anticoagulant therapy, 34 (28.5%) on antiplatelet drugs (ASA, thienopyridines or both), 4 (3%) on both warfarin and an antiplatelet agent, whilst 12 patients (10%)

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 were untreated. The prevalence of EGD UGI peptic lesions was 69 and 73% in patients treated with antiplatelets or warfarin, respectively (p = 0.83). Overall, there was a nonsignificant trend for a higher prevalence of EGD UGI lesions among patients with markers of a worse cardiac function, such as higher NT-pro-BNP and lower cardiac index. We were unable to perform EGD in 13 patients (8 refused; 5 due to hemodynamic instability). Among the remaining 121 patients, EGD was well tolerated despite none of them received conscious sedation. No complications were reported apart from one case of asymptomatic bradicardia, that did not preclude the procedure. Conclusions: In patients with advanced heart failure due to cardiomyopathy, there is a very high prevalence of UGI disorders. Among these, gastritis, cardias incontinence with esophagitis and hiatal hernia prevail. Most patients with EGD lesions are asymptomatic and, although widely implemented, prophylaxis with PPI/H2-A did not appear to reduce the prevalence of peptic lesions. Moreover, antiplatelet treatments did not seem to cause an excess toxicity among these patients compared to warfarin. Although EGD is an invasive procedure, it was well tolerated and safe when performed in hospital in congestive heart failure patients. This, together with the high prevalence of mucosal lesions and the potential ensuing risk, suggests that heart failure patients should not be denied an EGD whenever they report UGI symptoms.

Is NASH associated with high-though-normal tsh and lower cholesterol levels? S. Ballestri1, L. Carulli1, A. Lonardo1, F. Lami1, E. Violi1, L. Losi2, L. Bonilauri1, A.M. Verrone1, M.R. Odoardi1, F. Scaglioni1, M. Bertolotti1, P. Loria1 University of Modena and Reggio Emilia, Modena, Italy; 1 Department of Internal Medicine, Endocrinology, Metabolism and Geriatrics, Nuovo Ospedale Civile S.Agostino-Estense; 2Department of Pathology, Azienda Ospedaliero-Universitaria Policlinico, Italy Background: Hypothyroidism is associated with the risk of metabolic syndrome (MS) and hypercholesterolemia. Direct evidence that hypothyroidism might be associated with advanced chronic liver disease via nonalcoholic steatohepatitis (NASH) is limited. We studied the relationship between thyroid hormones, thyroid stimulating hormone (TSH), cholesterol and NASH. Methods: In consecutive euthyroid patients with biopsy-proven nonalcoholic fatty liver disease, TSH and thyroid hormones (FT3 and FT4) concentrations were compared in 25 with steatosis and 44 noncirrhotic NASH patients featuring concurrent ballooning, lobular inflammation and steatosis. MS was diagnosed according to ATPIII criteria. A metanalysis of previously published studies was performed to evaluate whether NASH, compared to simple steatosis, is associated with lower cholesterol levels. Results: At univariate analysis, compared with those with steatosis, patients with NASH had higher waist, BMI, ALT, AST, fasting insulin, HOMA-IR, ferritin, TSH and lower serum cholesterol. At stepwise multivariable logistic regression analysis the independent predictors of NASH were: high HOMA and TSH and lower total cholesterol (Model 1); MS and high TSH (Model 2). At metanalysis (Fig. 1) serum total cholesterol levels are significantly lower in predominantly non-cirrhotic NASH than in simple steatosis. Conclusions: This study provides cross-sectional and metanalytic evidence that, in euthyroid patients, high-though-normal TSH values

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 are independently associated with NASH. Further work is needed to ascertain the role, if any, of lower cholesterol serum levels in assisting in the diagnosis of NASH.

S263 p = 0.035; ALT: q = 0.317; p = 0.022; bilirubin: q = 0.302; p = 0.041). US-FLI was significantly associated with steatosis extent assessed histologically (0.745; p \ 0.001), lobular inflammation (0.616; p \ 0.001), ballooning (0.478; p = 0.001), NAS score (0.679; p \ 0.001) and NASH grade (0.511; p \ 0.001). No correlations were found between US-FLI and fibrosis and portal inflammation. US-FLI was an independent predictor of NASH (OR 2.236; p = 0.007). US-FLI predicts NASH diagnosed according to Brunt’s criteria (AUC: 0.763, 95% CI: 0.634–0.893; p = 0.002) and NAS (AUC: 0.796, 95% CI: 0.676–0.916 p \ 0.001). The best cut-off values of US-FLI for detecting the presence of NASH were 4 for Brunt’s and 5 for Kleiner’s classification. Furthermore a US-FLI \ 4 had a high negative predictive value (94%) in ruling out the diagnosis of NASH according to Kleiner’s criteria. Conclusion: Data confirm the hypothesis that, being associated with metabolic derangements and with individual histological items of liver histology, US-FLI may assist in identifying those patients to submit to liver biopsy.

Erythropoietin alpha 40.000 IU increases haemoglobin levels and improves sustain virological response in combination therapy with peg-interferon/ribavirin in chronic hepatitis C Fig. 1 Meta-analysis of data on serum cholesterol levels in NASH as opposed to simple steatosis. The size of squares indicating mean values is proportional to the weight that each study contributed to the aggregated result. Aggregated means with 95% confidence intervals are shown by diamond symbol. CI confidence interval. Cohen’s Q Heterogeneity Chi-squared test = 19.02 (df = 16) p = 0.268. I-squared index = 15.9%. Test of standardized mean difference (SMD) = 0: z = 2.17, p = 0.030

Ultrasound-fatty liver indicator (US-FLI), a novel ultrasonographic score, rules out NASH and is correlated with metabolic parameters in NAFLD S. Ballestri1, A. Lonardo1, D. Romagnoli1, L. Carulli1, L. Losi2, Cp. Day3, P. Loria1 1 Department of Internal Medicine, Endocrinology, Metabolism and Geriatrics; 2Department of Pathology, University of Modena and Reggio Emilia, Modena, Italy; 3Institute of Cellular Medicine, Newcastle University Medical School, Newcastle upon Tyne, UK

Background: Differentiating hepatic steatosis from Non-alcoholic steatohepatitis (NASH) is key in deciding treatment and follow-up schedules. We hypothesized that, being correlated with metabolic changes, the extent of steatosis, to which ultrasonography scanning is reported to be sensitive, might be associated with NASH. Methods: Fifty-three patients with biopsy proven Non-alcoholic fatty liver disease (NAFLD) underwent a semiquantitative evaluation of hepatic steatosis through Ultrasound-Fatty Liver Indicator (US-FLI). US-FLI is a new scoring system ranging 2–8, which is based on the intensity of liver/kidney contrast, posterior attenuation of ultrasound beam, vessel blurring, difficult visualization of gallbladder wall or diaphragm and areas of focal sparing. In the appropriate clinical setting, NAFLD is diagnosed by a minimum score C2 US findings were correlated with metabolic and histological data. Results: US-FLI showed a significant positive correlation with metabolic parameters exploring insulin resistance and hepatocellular function/damage (HOMA: q = 0.393; p = 0.006; insulin: q = 0.403; p = 0.005; uric acid: q = 0.293; p = 0.039; ferritin: q = 0.291;

G. Bertino, A. Ardiri, G.S. Calvagno, P.M. Boemi, C.M. Bruno, M. Valenti, S. Neri Department of Internal Medicine and Systemic Diseases, Hepatology Unit AOU Policlinic-Vittorio Emanuele, Policlinic ‘‘Gaspare Rodolico’’ University of Catania, Italy Background: The conventional antiviral treatment of chronic hepatitis related to hepatitis C virus (HCV) often leads to anaemia. In this case, it is necessary to reduce ribavirin dose or stop treatment, thus reducing the rate of sustained virological response (SVR). Aim: We investigated whether erythropoietin alpha administration improves treatment adherence and leads to higher percentage of response at the end of therapy and sustained virological response. Methods: One hundred and ten individuals with genotype 1b HCVrelated chronic hepatitis underwent treatment with pegylated (peg)interferon alpha-2A 180 lg once weekly and ribavirin 1,000–1,200 mg/day; 90 were responders. Twenty-one individuals completed treatment with no haemoglobin reduction; 69 developed anaemia during therapy. Anaemic responders were distributed randomly into two groups: group 1 continued therapy with erythropoietin alpha addiction; group 2 continued antiviral therapy with ribavirin reduction only. Results: Patients in group 1 achieved better control of haemoglobin levels (13.6 ± 1.2 g/dl at the end of therapy) than those in group 2 (11.5 ± 0.8 g/dl). Asthenia, Loss Concentration, Insomnia (L.A.S.A. score) was 13% in group 1 and 96,9% in group 2 (p \ 0.001). Sustained virological response was 62.8% in group 1 compared with 32.3% in group2 (p \ 0.001). Conclusions: In patients with 1b HCV-related chronic hepatitis who develop anaemia during antiviral treatment, administration of erythropoietin alpha increases haemoglobin levels and the end-oftreatment rate and sustains virological response by improving treatment adherence.

Combination therapy with pegylated interferon alfa-2a and ribavirin causes a decrease in portal pressure in patients with chronic hepatitis c-related cirrhosis G. Bertino, A. Ardiri, G.S. Calvagno, P.M. Boemi, E. Basile, M. Proiti, S. Neri

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S264 Department of Internal Medicine and Systemic Diseases, Hepatology Unit AOU Policlinic-Vittorio Emanuele, Policlinic ‘‘Gaspare Rodolico’’, University of Catania, Catania, Italy Introduction: In patients with compensated hepatitis C-related cirrhosis (HC-Cirrhosis), an hepatic venous pressure gradient (HVPG) [10 mmHg (Clinically Significant Portal Hypertension, CSPHT) is associated with higher risk of hepatic decompensation and worse prognosis. In this setting, reduction of HVPG [10% of baseline has been shown to prevent complications from portal hypertension. Antiviral therapy is indicated in these patients, and preliminary data suggest a beneficial effect of antiviral therapy on HVPG. Aim: To assess, in patients with HC-Cirrhosis and CSPHT, the short and long-term effect of antiviral therapy with PegInterferon alfa-2a (180 lg weekly) and ribavirin (1,000–1,200 mg/d) (Combination Theraphy pegIFN plus RBV) on HVPG. Methods: In 26 patients (70% male, median age 53 ± 8) with HCcirrhosis and CSPH receiving antiviral therapy with pegIFN plus RBV, HVPG was determined at baseline and after 12 weeks of therapy. In 12 patients with early virological response (EVR: decrease [ 2 logs of viral load at week 12) HVPG was again measured 6 weeks after completing 48 weeks of treatment (9/12 SVR, and 3 without). In 14 patients without EVR, combination therapy pegIFN plus RBV was stopped and HVPG was again measured after a similar observational follow up period. Results: Genotype 1 represented 100% of all patients and median baseline viral load was log10 6.06 ± 0.54. At week 12, HVPG significantly decreased from 15.2 ± 3.0–13.5 ± 3.0 mmHg (p \ 0.001) with a median decrease of 9.0 ± 12.9%. In 12 patients, this reduction was [10% or below the 10 mmHg threshold (HVPG responders). HVPG responders were those with higher baseline viral load (6.4 ± 0.3 vs. 5.6 ± 0.6; p = 0.001) and those that had a greater reduction in viral load and ALT at week 12 (-4.0 ± 2.2 vs. -2.4 ± 2: p = 0.03 and -104 ± 72 vs. -52 ± 70 IU/L; p = 0.06 respectively in HVPG non-responders). In the 10 patients with SVR, the reduction in HVPG achieved at week 12 was maintained 6 weeks after completing antiviral therapy (12.8 ± 2.6 mmHg (12 weeks) to 12.4 ± 3.0; p = 0.2) while HVPG tended to increase in the 16 pts without SVR (from 13.2 ± 3.0 to 14.2 ± 4.0 mmHg; p = 0.05). Conclusion: Successful pegIFN plus RBV treatment significantly reduces HVPG in HC-cirrhosis and by this mechanism may prevent the portal hypertension-related complications.

Visceral fat accumulation plays both roles as the first and second hit in the pathogenesis of nonalcoholic fatty liver disease G. Bertino, A. Ardiri, G.S. Calvagno, P.M. Boemi, E. Basile, M. Proiti, S. Neri Department of Internal Medicine and Systemic Diseases, Hepatology Unit AOU Policlinic-Vittorio Emanuele, Policlinic ‘‘Gaspare Rodolico’’, University of Catania, Catania, Italy Background: Adiposity is important to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We recently indicated close association between visceral fat accumulation and hepatic steatosis. Aim: To investigate the role of visceral fat accumulation in the ‘‘two steps’’ development to nonalcoholic steatohepatitis (NASH). Methods: Study (1): Consequently, a total of 245 subjects who underwent health check-up and the measurement of visceral fat area (VFA, cm2). All subjects had no markers of HBV, HCV infection and excessive alcohol intake. The relationship between VFA and biochemical parameter were examined. Study (2): A total of 58 patients with NAFLD who underwent liver biopsy were included. The

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 association between visceral fat accumulation determined by abdominal ultrasonography and histopathology was assessed according to the NAFLD activity score (NAS) and fibrosis score. Histological activity is defined as follows; NAS [ 3, simple steatosis; 3 \ NAS [ 5, border line; NAS [ 5, definite NASH. Fibrotic stage is divided into F1/2 (early NASH) and F3/4 (advanced NASH). In patients who underwent programmed diet and exercise weight reduction therapy, the relationship between the change of visceral fat accumulation and various parameters were investigated. Results: Study (1): There was a significant relationship between VFA and fasting glucose (r = 0.329), HDL cholesterol (r = -0.464), LDL-cholesterol (r = 0.264), triglyceride (TG) (r = 0.349) and ALT (r = 0.476) levels (p \ 0.001, respectively). Stepwise regression analyses selected VFA, triglyceride and LDL as predictor variables for serum ALT level (serum ALT level = -0.852 + 0.154 9 VFA + 0.028 9 TG + 0.055 9 LDL, R2 = 0.240, p \ 0.001). Study (2): In patients with NAFLD, there was no significant difference in each histological activity. Visceral fat accumulation with F 3/4 was severer than F 1/2 (p \ 0.05). In patients achieved weight reduction, hepatic steatosis, ALT, lipids and insulin resistance were significantly associated with decrease of visceral fat accumulation (p \ 0.01). Conclusions: The first hit: visceral fat accumulation was positively related to serum ALT elevation even in healthy general population. Second hit: visceral fat accumulation was associated with fibrotic stage in NASH patients. These results suggested that visceral fat accumulation might influence the development of NAFLD as both the first hit and second hit.

Association between diabetes mellitus, hepatic steatosis and fibrosis in chronic hepatitis C patients G. Bertino, A. Ardiri, G.S. Calvagno, P.M. Boemi, C.M. Bruno, M. Valenti, E. Basile, M. Proiti, S. Neri Department of Internal Medicine and Systemic Diseases, Hepatology Unit AOU Policlinic-Vittorio Emanuele, Policlinic ‘‘Gaspare Rodolico’’, University of Catania, Catania, Italy Background: Glucose abnormalities and type 2 diabetes mellitus (DM 2) are a recognized extrahepatic manifestation of HCV infection. Hepatic steatosis is a common histologic feature in patients with chronic hepatitis C (CHC). Aims: The aims of the study were to elucidate the association between DM 2, steatosis and severity of fibrosis and the associations between these parameters and the virological characteristic in CHC patients. Methods: 27 CHC patients (16 males, mean age: 52 years, 23 with type 1b infection, 2 with type 2b infection, 2 with type 3a infection) were enrolled. CHC patients with positive for both anti-HCV antibodies and HCV RNA for at least 6 months, with biopsy-proven chronic hepatitis. Serum HCV RNA, HCV RNA levels and HCV genotypes 1a, 1b, 2a, 2b and 3a were determined. The liver histology were assessed using the Ishak scoring system and steatosis was quantified as the percentage of hepatocytes that contained fat droplets. Results: 35.8 and 22.7% patients have hepatic steatosis and severe fibrosis (F3–4), respectively. DM 2 was diagnosed in 17.8% patients. Multivariate logistic regression analyses showed that male gender, a higher ALT level, the presence of steatosis, severe fibrosis (F3–4) and a higher BMI were independent factors associated with DM (p \ 0.001). The presence of DM, a higher necroinflammatory score, and a higher BMI were independent factors associated with severe fibrosis in CHC patients (p \ 0.001). DM, a higher necroinflammatory score, and a higher BMI were independent factors associated with steatosis in CHC patients (p \ 0.001). The virologic characteristics

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 including HCV genotype and HCV RNA levels were not associated with DM 2, severe fibrosis and steatosis in CHC patients (p = ns). Conclusion: In conclusion, we found in this study that DM 2 was associated with histological characteristics of steatosis and severe fibrosis. DM 2, BMI and necroinflammation activity are factors commonly associated both steatosis and severe fibrosis. Both HCV genotype or HCV RNA levels play minimal roles in DM 2, steatosis and fibrosis in CHC patients.

Steatohepatitis influences the cardiovascular and diabetes mellitus risk profile G. Bertino, A. Ardiri, G.S. Calvagno, P.M. Boemi, C.M. Bruno, M. Valenti, E. Basile, M. Proiti, S. Neri Department of Internal Medicine and Systemic Diseases, Hepatology Unit AOU Policlinic-Vittorio Emanuele, Policlinic ‘‘Gaspare Rodolico’’, University of Catania, Catania, Italy Background: The cause of steatohepatitis can be due to alcohol abuse, viral infections, genetic dispositions, and among them, insulin resistance syndrome is the factor of greatest association. Nonalcoholic fatty lived disease (NAFLD) is linked to the metabolic syndrome. All of this conditions carrying a high risk of cardiovascular events and risk of developing Type 2 Diabetes Mellitus (DM). Aim: To calculate the 5-years risk of cardiovascular events and 5-years risk of developing type 2 DM in patient with alcoholic and nonalcoholic steatohepatitis. Methods: We measured the cardiovascular and DM risk profile in 50 NAFLD cases, 50 alcoholic liver diseases cases and 50 age and sex matched controls. The 5-years risk of cardiovascular events was calculated according to Framingham equation and the score derived from the PROCAM study and ATPIII proposal. The 5-years risk of developing type 2 DM - according to the QDScore diabetes equation. The risk score were categorized using predefined cutoffs as intermediate (B20%) and high ([20%). Results: The 5-years probability of cardiovascular event was moderately increased in NAFLD compared with controls, according to the Framingham (high risk - 36% vs 18%, p = 0.0001, Chi-squared test) and to the ATPIII (36% vs 18%, p = 0.0001, Chi-squared test) equation. On the contrary, when the risk were compared between subject with NAFLD and alcohol liver disease cases, we observed high risk according to the Framingham score in 36% vs 67% cases (p = 0.001, Chi-squared test) respectively and to the ATP III scope - in 36% vs 52% cases (p = 0.001, Chi-squared test) respectively. No different were observed when the risk were compared according PROCAM equation. Predicting risk for type 2 DM according to the QDScore was increased in NAFLD compared with controls (high risk - 65% vs 42% cases, p = 0.0001, Chi-squared test) and with alcoholic liver disease cases 65% vs 52% cases (p = 0.014, Chi-squared test) respectively. Conclusion: Patients with NAFLD had increase 5-years risk of cardiovascular events and developing of type 2 DM in comparison of controls matched by age and sex. The 5-years risk of cardiovascular events were higher in cases of alcohol liver disease, than in NAFLD.

Suboptimal endogenous erythropoietin response in chronic hepatitis C patients during peg-interferon and ribavirin treatment

S265 Background: During the treatment of hepatitis C, anaemia may necessitate pegylated-interferon and ribavirin dose reductions with reduced sustained viral response rates. Although erythropoietic growth factors are frequently used to improve anaemia, it is controversial whether endogenous erythropoietic response is insufficient under these circumstances. Aim: We aimed to identify risk factors for more pronounced anaemia and to evaluate endogenous erythropoietic response during antiviral therapy. Methods: Two hundred and fourteen individuals with genotype 1b HCV-related chronic hepatitis underwent treatment with pegylated (peg)-interferon alpha-2A 180 lg once weekly and ribavirin 1,000-1,200 mg/day; 174 were responders. All patients were evaluated for haemoglobin, haematocrit, serum ribavirin and erythropoietin levels. Results: 134/214 (77%) of patients developed anaemia, with maximal decrease in haemoglobin of 2.5 ± 1.0 mmol/l (range 0.3-5.5 mmol/l). Older age, lower baseline creatinine clearance, higher baseline haemoglobin, more pronounced haemoglobin decrease after 2 weeks and higher week 24 serum ribavirin concentrations were independent risk factors for more pronounced anaemia. Serum erythropoietin levels increased from median 12 IU/l (range 4-63 IU/l) at baseline to 41 IU/l (range 12-683 IU/l) after 12 weeks of therapy and to 43 IU/l (range 7-3238 IU/l) at week 24 (P \ 0.001). Erythropoietin levels at baseline, week 12 and week 24 negatively correlated with haematocrit. The erythropoietic response to anaemia in our study population was significantly different from the normal human response to anaemia. Conclusion: Older age, lower baseline creatinine clearance, higher baseline haemoglobin, more pronounced haemoglobin decrease after 2 weeks and higher week 24 serum ribavirin concentrations were independent risk factors for more pronounced anaemia during antiviral therapy. Endogenous erythropoietin production is suboptimal during antiviral therapy, supporting use of erythropoietic growth factors.

HCV infection and liver cirrhosis Child-Pugh B-C were associated insulin resistance G. Bertino, A. Ardiri, G.S. Calvagno, S. Neri Department of Internal Medicine and Systemic Diseases, Hepatology Unit AOU Policlinic-Vittorio Emanuele, Policlinic ‘‘Gaspare Rodolico’’, University of Catania, Catania, Italy Background: Several clinical studies have suggested a possible link between chronic hepatitis caused by hepatitis B virus (HBV)/Hepatitis C virus (HCV) and diabetes mellitus. Aims: We investigated the association between clinical data and glucose intolerance in HBV/HCV infected patients. Methods: A total 68 HCV infected patients and 60 HBV infected patients were recruited into this study. We evaluated insulin resistance (homeostasis model assessment of insulin resistance [HOMA-R]) and beta-cell function (homeostasis model assessment of beta-cell function [HOMA-b]) in a fasting state an after an oral 75 g glucose (whole-body insulin sensitivity index [WBISI]) and D-insulin 30/Dglucose 30). HBV/HCV infected patients divided into three subgroups:

G. Bertino, A. Ardiri, G.S. Calvagno, P.M. Boemi, C.M. Bruno, M. Valenti, S. Neri

1) 2) 3)

chronic hepatitis (CH), liver cirrhosis with child-Pugh C stage (LC-C), liver cirrhosis with child-Pugh B (LC-B)

Department of Internal Medicine and Systemic Diseases, Hepatology Unit AOU Policlinic-Vittorio Emanuele, Policlinic ‘‘Gaspare Rodolico’’, University of Catania, Catania, Italy

according clinical data including biochemical parameter, serum virus load were quantified by real-time PCR, histological score, (Ishak score), CT scanning and gastroscopy.

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S266 Results: Multivariate analysis shows HCV infection and advanced liver cirrhosis the two keys independent factors associated with insulin resistance (p \ 0.001). HOMA-R was significant higher in HCV infected patients when compared with HBV infected patients. When patients were divided into CH, LC-C and LC-B sub-groups, HCV infected patients with child-Pugh stage C sub-group has the highest HOMA-R with 6.22 (p \ 0.001). Conclusions: Our findings suggest that HCV infection and the advanced liver cirrhosis are associated to insulin resistance.

Vitamin K administration in patients with hepatocellular carcinoma decreases des-gamma carboxy prothrombin but not alpha-fetoprotein serum levels G. Bertino, A. Ardiri, G.S. Calvagno Department of Internal Medicine and Systemic Diseases, Hepatology Unit AOU Policlinic-Vittorio Emanuele, Policlinic ‘‘Gaspare Rodolico’’, University of Catania, Catania, Italy Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world and, in most cases, is diagnosed at a late stage. Des-gamma carboxy prothrombin (DCP) is increased in the serum of patients with HCC. In hepatoma cells, genetic alterations, membrane receptors, the inability to uptake labelled low-density lipoprotein, cytoskeletal changes and hepatocyte cytoplasmic transfers involved in vitamin K metabolism could play an important role in producing detectable DCP serum levels. More recent research has demonstrated that DCP has potential for both autocrine and paracrine stimulation in the development of HCC. Aim: The aim of this study is to examine whether intravenous administration of vitamin K in HCC patients DCP positive is able to reduce DCP serum levels, and therefore, its potential effect on tumor growth. Methods: My colleagues and I have studied the effect of vitamin K administration on DCP and alpha-fetoprotein (AFP) production in patients with HCC; we also measured serum concentrations of vitamin K to identify a relationship between vitamin K and DCP serum levels. In 64 caucasian patients, 54 males and 10 females (mean age 65 ± 5 years) with HCC, that was diagnosed by both radiological and histological investigations (ultrasonography, computed tomography, magnetic resonance imaging, biopsy and, where were necessary, hepatic angiography), serum levels of AFP, DCP and Vitamin K have been determined. Patients positive for AFP and DCP were re-tested after intravenous administration of phytomenadione (vitamin K1), 20 mg/day for ten consecutive days. Control group consisted of 60 subjects, 49 males e 11 females (mean age 62 ± 3 years), with cirrhosis but without HCC. Subjects with jaundice, hematochemical signs of cholestasis or who had been treated with broad spectrum antibiotics or oral association therapy of neomycin and bacitracin, as well as cirrhotics with CHILD B or C were excluded. Results: Forty-seven out of sixty-four patients (47/64: 74%) had detectable DCP with a mean level of 94.0 ± 10 mAU/ml; 43/64 (68%) were AFP positive with a mean of 280.0 ± 40 IU/mL. The 47 DCP-positive and 43 AFP-positive patients were re-tested after intravenous administration of phytomenadione (vitamin K1), 20 mg per day, for ten consecutive days. After vitamin K administration, in 37/47 (78.7%) subjects positive for DCP, we observed a reduction in DCP serum levels below the cut-off of 40 mAU/mL (with a mean value of 12 mAU/ml; in 10/47 (21.2%) subjects we also observed a reduction in DCP levels from baseline values, but they were above cut-off of 40 mAU/ml (with a mean value of 74.6 mAU/ml). Instead, after administration of vitamin K we did not observed any variation in

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 AFP serum levels compared to baseline values. No correlation was observed between vitamin K concentration and DCP level: vitamin K concentration was similar in the HCC group and in the control group without HCC; HCC patients had the same vitamin K concentrations regardless of their DCP levels after vitamin K administration. In patients with HCC, baseline serum values of DCP and AFP, obtained before vitamin K administration, were compared with serum levels of DCP and AFP determined after ten days of vitamin K administration; it was applied a t-test for unpaired data, resulting in a difference statistically significant (p \ 0,05) only for DCP values. In thirtyseven patients with reduced DCP serum levels after vitamin K administration was re-dosed to the DCP 4, 8, 10, 12 days after discontinuation of vitamin K. In all, serum levels of DCP have returned to baseline value (95.5 ± 10 mAU / ml * p \ 0.05). Conclusions: Our results show that vitamin K administration inhibited DCP production in a dose dependent manner but had no effect on AFP production. More recent research has demonstrated that DCP stimulates human vascular endothelial cell growth and migration and DCP has potential for both autocrine and paracrine stimulation in the development of HCC. The inhibition of DCP production could be considered an effective strategy in the treatment of HCC, DCP positive. Therefore, administration of vitamin K as a new option for HCC treatment to be associated with well established therapeutic strategies in evidence-based medicine. However, this hypothesis will be tested in a large number of patients in multicenter clinical controlled trials, also more data are necessary to clarify when vitamin K treatment should be started, the duration of treatment, the optimal dosage.

Th1 low & Th2 high producer genotypes are characteristic of Whipple’s disease F. Biagi, A. Marchese, L. Trotta, P.I. Bianchi, C. Vattiato, D. Balduzzi, A. Zilli, A. Schiepatti, V. Staffieri, C. Alfano, M. Di Stefano, G.R. Corazza First Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy Introduction: Since Whipple’s disease (WD) is a chronic systemic condition due to a dysregulated Th1/Th2 response versus Tropheryma whipplei [1], we investigated whether WD is associated to Th1 cytokines low producer status and/or Th2 cytokines high producer status. Methods: Thanks to the European Consortium on WD (QLG1-CT2002-01049) genomic DNA was analysed for both Th1 and Th2 cytokines genes in 111 German patients suffering from WD by means of PCR-SSP. Results were compared with those obtained in 200 healthy German controls. Results:

Low Th1 producer status

High Th2 producer status 0-1

2

WD vs Con.

WD vs Con.

0-1 2

4,5 vs 9,5 25,2 vs 27,4

Ref 0,7-5,7

0 vs 1,5 5,4 vs 4,0

na 0,7-12,1

[2

46,8 vs 45,8

0,8–6,1

18,0 vs 11,9

1,0-10,0*

* p \ 0,05

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Conclusions: Th1 low & Th2 high producer genotypes are more frequent among patients with WD than controls. Patients with WD are genetically predisposed to a low Th1/high Th2 response. These results parallel cellular findings [2]. References 1. Marth. Gastroenterology. 2002;123:1468 2. Moos. J Immunol. 2006;177:2015

Refractory coeliac disease in Italy: a multicentric study F. Biagi1, A. Marchese1, R. Ciccocioppo1, U. Volta2, C. Ciacci3, A. D’Odorico4, A. Carroccio5, A. Gasbarrini6, G.R. Corazza1 1 Policlinico San Matteo,University of Pavia, Pavia; 2St OrsolaMalpighi University Hospital,Bologna; 3Federico II University, Naples; 4University of Padua; 5University of Palermo, 6Catholic University of Sacred Heart, Gemelli University Hospital, Rome, Italy

Introduction: Coeliac disease (CD) is a very frequent chronic enteropathy characterized by an increased mortality. Several papers showed that the increased mortality is mostly due to serious conditions known to complicate CD. Our aim was to organize a multicentre study focusing on complicated CD (CCD) in Italy. Patients and Methods: Thanks to Fondazione Associazione Italiana Celiachia that funded the study, we collected clinical data from Italian patients affected by CCD. RESULTS. 6 Italian centres joined the project and 76 patients (47 females, age at diagnosis of CD 50 ± 15 years) were enrolled. Gluten-free diet adherence was considered to be rigorous only in 76% of patients. Complications were represented by 27 refractory CD, 14 T-lymphomas, 13 ulcerative jejunal-ileitis, 12 small bowel adenocarcinomas, 7 B-lymphomas, 1 colon cancer, 1 Hodgkin lymphomas, 1 cutaneous lymphoma. In 47 cases the onset of complications followed the diagnosis of CD (4.5 ± 4 years), in 3 cases the diagnosis of CD followed that of complications and in the remaining cases the two diagnoses were almost at the same time. 30 patients died; only 5 of them for reasons not related to CCD. Among patients who died from CCD, the time between diagnosis of CCD and death was 2 ± 2 years. Conclusions: This is the first multicentre study performed in Italy on CCD. These epidemiological results are very preliminary but nevertheless they confirm that CCD is an extremely serious condition with a very high mortality and a very short survival. The onset of CCD is certainly related to late diagnosis and poor compliance to a glutenfree diet. [Biagi F, Corazza GR. Nat Rev Gastroenterol Hepatol. 2010;7:158–62; Biagi F, Corazza GR. Ann Med. 2010;42:557–61].

The matrix metalloproteinases produced in excess in inflamed gut degrade therapeutic antibodies and soluble receptor fusion proteins which target TNF-alpha P. Biancheri1, A. Di Sabatino1, Sa. Snoek2, I. Joe-Njoku2, L. Rovedatti1, N. Ahmad2, T.T. Macdonald2, G.R. Corazza1 1 First Department of Medicine, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy; 2Centre for Immunology and Infectious Disease, Blizard Institute of Cell and Molecular Science, Barts and The London SMD, London, UK

Background and Aims: A considerable proportion of inflammatory bowel disease (IBD) patients fail to respond to anti-tumor necrosis factor (TNF)-alpha treatment. Several matrix metalloproteinases (MMPs) can cleave human IgG proximally to the hinge region. AntiTNF-alpha agents are IgG or contain part of the IgG sequence. We

S267 therefore investigated the cleavage of anti-TNF-alpha agents by MMPs that are up-regulated in IBD inflamed mucosa, namely MMP3, -8, 10 and -12. Materials and Methods: Activated recombinant human MMP-3, -8, -10 or -12 were incubated with infliximab, adalimumab, certolizumab pegol or etanercept. IgG Fc portion or Ig kappa light chains were detected by immunoblotting on the supernatants collected at 0, 3, 6, 10 and 24 h. The ability of MMP-treated antibodies to neutralise TNF-alpha was tested using a luciferase reporter cell line. Mucosal homogenates from inflamed areas of 6 IBD patients and from normal gut of 6 control subjects were depleted of endogenous IgG and incubated for 24 h with the four drugs, then immunoblotted for human IgG Fc portion or kappa light chains. Results: Certolizumab pegol was not cleaved by any of the MMPs tested. Infliximab and adalimumab were degraded only by MMP-3 and -12, releasing 32 kDa Fc monomers and F(ab)2. Etanercept was cleaved by MMP-3, -10 and -12, although Fc monomers were found only after MMP-3 and -12 digestion. All the four drugs inhibited luciferase production in TNF-alpha-stimulated HeLa 57A cells. When the anti-TNF-alpha agents were pre-incubated with activated MMP-3, -10 or -12, only etanercept lost its ability to inhibit luciferase production. None of the anti-TNF-alpha agents were degraded by the control mucosa, whereas etanercept was cleaved by IBD tissue. Conclusions: Adalimumab and infliximab are functioning as F(ab)2 fragments after degradation by MMP-3 and -12, whereas etanercept is unable to neutralise soluble TNF-alpha after MMP-cleavage. These findings provide a possible explanation for the clinical inefficacy of etanercept in IBD patients.

Involvement of gut macrophages in the fibrogenic process in Crohn’s disease P. Biancheri1, A. Di Sabatino1, A. Ghanbari1, S.A. Snoek2, T.T. Macdonald2, G.R. Corazza1 1

First Department of Medicine, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy; 2Centre for Immunology and Infectious Disease, Blizard Institute of Cell and Molecular Science, Barts and The London SMD, London, UK Background and Aims: Intestinal fibrosis and stricture formation are a frequent complication of Crohn’s disease (CD). Cytokine driven excessive extracellular matrix deposition and an imbalance between matrix metalloproteinases (MMPs) and their inhibitors are thought to play an important role in the transmural process of stricture development. We have therefore investigated the immunological changes occurring in the deeper layers of the bowel wall in inflammatory bowel disease and control ileum or colon. Materials and Methods: Surgical specimens were collected from strictured and non-strictured gut of 10 CD patients, from inflamed gut of 8 ulcerative colitis (UC) patients, and from normal gut of 10 control subjects. The mucosa was removed and discarded. Immunohistochemistry on muscle layers was performed using anti-CD3, -CD4, -CD8, -HLA-DR, and -CD68 antibodies. Explants of strictured, non-strictured CD and control gut were cultured ex vivo for 24 h. MMP-3 expression and collagen, interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha levels were measured in organ culture supernatants. Results: HLA-DR+ cells and macrophages (CD68+ cells) were significantly increased in intestinal CD strictures as compared to inflamed UC and control gut. No significant differences were found in total T (CD3+), CD4+, and CD8+ cell frequency among the three groups of patients, and in general T cells were infrequent. Collagen and IL-1beta were significantly increased in organ culture

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S268 supernatants from strictured CD as compared to those from nonstrictured CD and control gut. IL-6, TNF-alpha and MMP-3 expression did not differ between strictured, non-strictured CD and control gut supernatants. Conclusions: The increased frequency of CD68+ cells in CD strictures and the high levels of IL-1beta in strictured CD supernatants suggest that macrophages may play an important role in driving the processes of fibrogenesis in CD. As different subpopulations of macrophages have been shown to exert pro- or anti-fibrogenic in vitro effects on human fibroblasts, further ongoing functional studies are aimed at identifying and altering macrophage function in strictured CD tissue.

Is ulcerative colitis an atypical Th2-mediated disease characterised by excess production of IL-13? P. Biancheri1, A. Di Sabatino1, S.A. Snoek2, I. Joe-Njoku2, L. Rovedatti1, C. Ubezio1, M. Guerci1, P. Giuffrida1, A. Quadrelli1, N. Ahmad2, T.T. Macdonald2, G.R. Corazza1 1

First Department of Medicine, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy; 2Centre for Immunology and Infectious Disease, Blizard Institute of Cell and Molecular Science, Barts and The London SMD, London, UK Background & Aims: Interleukin (IL)-13 is produced mostly by T helper cell type (Th)2 cells and, together with IL-5, it has been supposed to be a major cytokine implicated in sustaining the pro-inflammatory immune response in ulcerative colitis. We have therefore assessed IL-13 and IL-5 production by inflamed mucosa and isolated lamina propria mononuclear cells (LPMCs) from ulcerative colitis patients, and evaluated the effect of IL-13 or its neutralization on the intestinal immune response in inflammatory bowel disease. Methods: Biopsies and LPMCs from the inflamed colon of 11 ulcerative colitis patients and 9 Crohn’s disease patients, and from normal colon of 15 control subjects were cultured ex vivo with or without anti-CD3/CD28-antibodies. IL-13, IL-5, IL-17 and interferon (IFN)-c production was measured by ELISA in the cell and organ culture supernatants. Anti-CD3/CD28-stimulated LPMCs were also cultured with recombinant human IL-13 or with an anti-IL-13 neutralizing antibody, and the production of IFN-c, IL-17 and tumor necrosis factor (TNF)-a was determined by ELISA. Results: Ex vivo IL-13 production did not differ between ulcerative colitis, Crohn’s disease and control biopsies, although IFN-c and IL17 were significantly higher in ulcerative colitis and Crohn’s disease than in controls. Anti-CD3/CD28 stimulation induced a small increase in IL-13 production without significant differences between the three groups, whereas IFN-c and IL-17 production by LPMCs was significantly higher after anti-CD3/CD28 stimulation. IL-5 was undetectable in all the organ culture or LPMC supernatants. The addition of recombinant IL-13 or the neutralization of endogenous IL13 did not induce any significant change in IFN-c, IL-17A and TNF-a production by anti-CD3/CD28-stimulated ulcerative colitis and Crohn’s disease LPMCs. Conclusions: IL-13 does not seem to be involved in modulating the mucosal immune response in ulcerative colitis and the Th2 response may play a minor role compared to Th1 and Th17 responses in driving mucosal inflammation in inflammatory bowel disease.

IgM-linked serpinb3 and serpinB4 in serum in chronic liver disease A. Biasiolo1, N. Tono2, L. Beneduce3, G. Fassina3, A. Gatta1, P.Pontisso1

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 1 Department of Clinical and Experimental Medicine ‘‘G. Patrassi’’, Padova; 2Istituto Oncologico Veneto IOV, Padova; 3Xeptagen SpA, Venice, Italy

Introduction: Epidemiological studies indicate that a growing number of cirrhotic patients will develop primary liver cancer in the next decade. To date, biomarkers with high diagnostic accuracy are still lacking. Recent findings have demonstrated that serpinB3 (SCCA1) and serpinB4 (SCCA2) are over-expressed in primary liver cancer and lower concentrations are detectable in patients with cirrhosis and chronic hepatitis, but not in normal liver. We have reported previously that high levels of circulating SCCA-IgM complexes in patients with cirrhosis are significantly associated to liver tumour development. Aims: To investigate whether IgM-linked SCCA isoforms circulate in patients with different extent of liver disease and with primary liver cancer and to define their distribution patterns, compared to total SCCA-IgM levels. Patients: Serum samples of 79 patients with chronic HCV infection were studied, including 17 patients with chronic hepatitis (M/F 11/6; mean age 53 ± 13 years), 36 patients with cirrhosis (M/F 23/13; mean age 64 ± 13 years) and 26 patients with hepatocellular carcinoma (M/F 19/7; mean age 64 ± 12 years). Cirrhotic patients were subgrouped as follow: group A included 17 patients who developed hepatocellular carcinoma (HCC) during a median follow-up of 4 years, group B included 19 patients without disease progression during the same follow-up. Serum samples from 28 blood donors were used as control. Methods: Monoclonal antibodies against serpinB3 and serpinB4 (CanAg, Sweden) were used as catcher antibodies to set up specific ELISA assays, while total SCCA-IgM immune complexes were detected by ELISA (Hepa-IC, Xeptagen). Results: A better diagnostic sensitivity of total SCCA-IgM (58%), compared to both serpinB3 (23%) and serpinB4 IgM-linked assays (35%) was detected. Patients with liver cirrhosis represented the group with the highest levels of both serpinB3-IgM and serpinB4IgM, especially the subgroup of patients who progressed to hepatocellular carcinoma. A decreasing trend of serpinB4-IgM/serpinB3-IgM median ratio occurred comparing patients with chronic hepatitis (1.40 range 1.04.5), patients with cirrhosis (1.10 range 0.9-6.2) and with HCC (1.08 range 0.4-4.2). This behaviour was mainly due to lower serum levels of serpinB4-IgM in patients with liver tumour. Conclusions: SerpinB3-IgM and SerpinB4-IgM are not superior to total SCCA-IgM assay for the diagnosis of HCC in serum. The relative balance of the two serpin isoforms is altered in HCC and it is characterized by a lower serpinB4-IgM/serpinB3-IgM median ratio value, determined by lower serpinB4-IgM levels.

Final results of a phase II study with sunitinib malate in advanced hepatocellular carcinoma M. Biolato, M. Basso, V. Vero, G. Marrone, A. Forgione, L. Miele, M. Pompili, G.L. Rapaccini, A. Gasbarrini, C. Barone, A. Grieco Institute of Internal Medicine, Catholic University of Sacred Heart, Rome, Italy Background: Since 2007, antiangiogenic therapy has been proved to be effective on the treatment of hepatocellular carcinoma (HCC). Sorafenib is the first drug of this class with the proved ability to improve overall survival (OS) and time to progression (TTP) when compared to best supportive care in patients with advanced HCC and a good liver function (Child A). Sunitinib is another multi-kinase

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 inhibitor that is active against VEGF-R, PDGF-R and c-KIT. We designed a phase II study, according to the two-step Simon’s model, to assess safety and efficacy and to explore biomarker of response of sunitinib in HCC patients. Methods: Eligibility criteria were: unresectable or metastatic HCC; no prior chemotherapy. PS (ECOG) 0-1; measurable disease according to RECIST criteria. Child C patients were excluded. Schedule: 50 mg each day, four weeks on, two weeks off. CT scan: every two cycles. PET-TC scan: at baseline and after the first cycle. Primary end-point was response rate according to RECIST criteria. Secondary end-points were OS, TTP and safety. Results: Between 6/2007 and 4/2010, 34 patients were enrolled (80% Child A and 20% Child B). 97 cycles were administered. Grade 3/4 adverse effects occurred in 80% of patients and included fatigue (47%), nausea (15%), liver failure (15%), hepatic encephalopathy (12%) and upper gastrointestinal bleeding (12%). Seven pts (21%) required dose reductions because of toxicity. Six pts (18%) died within 60 days since enrollment. Three of them belonged to Child B group and died because of liver failure. Two Child A patient had a bone metastasis to the clivus and and a large bleeding soft tissue metastasis, respectively, while the last Child A patient had a probable toxic death. A partial response was observed in 4 patients (12%) and the median duration of response was 17.5 months. Eleven patients (32.4%) experienced a disease stabilization, while 18 (52.9%) progressed. Median TTP was 5,6 months (0,5-26,3; CI 95% 3,9-7,2) and median OS was 8,2 months (0,5-31,9; CI 95% 6,5-9,7). Early metabolic response at PET-TC scan correlate with RECIST response in 83,3% patients (p = 0,042). Conclusion: The dose of 50 mg/d seem to induce an high frequence of severe adverse event. However, sunitinib is able to induce a prolonged response in some patients; PET-scan may select good responders.

A population study on manifestations of fructose intolerance in adults L. Bonfrate1, K. Ulst2, V. Ruggiero1, A. Dilillo1, P. Dambrosio1, I.O. Gonc¸alves3, G. Palasciano1, P. Portincasa1

S269 producing intestinal microflora and calculate orocecal transit time (lactulose 10 g p.o.), to diagnose fructose intolerance/malabsorption (50 g fructose) and lactose intolerance /malabsorption (lactose 25 g). Symptoms such as abdominal pain/bloating (Visual Analogue Scale, VAS 0-100 mm) and fecal consistency (Bristol Scale Form, BSF, score 1-7), were scored. Subjects with fructose intolerance were checked after 6-9 mo. by a lifestyle questionnaire (MEDSTYLE) to investigate their self-dietary changes and behaviors, and calculate fructose threshold causing symptoms. Winfood (Medimatica, Teramo, Italy) was therefore used to construct a 3 mo. personalized diet in which fructose threshold was divided into 4 daily portions of fruit/ vegetables. Results: 53 (72%) subjects had fructose intolerance (16M, 37F; mean age 41.4 ± 15.0 and 41.6 ± 15.1 yrs, body size 23.3 ± 4.5 and 23.4 ± 4.4 kg/m2, respectively P = NS). Symptom prevalence was: abdominal pain 79%, bloating 70%, diarrhea (self-perception: 45%, true 60%, P = NS), alternating bowel 11%. A concomitant diagnosis of lactose intolerance was made in 60% of subjects (N = 32). A program of lifestyle reeducation was started in 38 (72%) subjects. After 6-9 months 29 subjects (76%) had changed their habits: reduction of all fructosecontaining foods (fruit, sweets, vegetable, beverages) (45%) or only fruit and sweets (31%); total deprivation of all fructose-containing foods (17%) or only fruit and sweets (6%). All subjects had stopped honey ingestion. Overall, the number of weekly fruit/vegetable portions (1 portion = 150 mg) was 12.5 ± 7.0 (P \ 0.001 vs. WHO recommended weekly intake of 35 ± 0.0 portions). In 38% of subjects a weight loss was documented (3.5 ± 1.4 kg within 6.5 ± 3.3 mo.). Trigger fructose intake was 6.71 ± 2.1 g/day. Following the fructose-controlled personalized diet, 5% of subjects had complete benefit, 67% amelioration, 29% unchanged. Overall, daily evacuations and BSF decreased (from 3.0 ± 1.5 to 1.56 ± 0.58, P \ 0.001 and from 4.9 ± 1.6 to 4.0 ± 0.7, P = 0.008, respectively). Conclusions: Fructose intolerance is a frequent cause of unspecific gastrointestinal symptoms mimicking other organic and functional conditions and, in a tertiary referral center, requires a careful and complete diagnostic workup, to avoid unnecessary costs due to repeated consultations or delayed diagnoses. We suggest to develop a personalized alimentary programme according to the threshold fructose, to evaluate the improvement of symptoms.

1

Clinica Medica ‘‘A. Murri’’, DIMIMP, Universita` degli Studi di Bari, Bari, Italy; 2University Medical School of Tartu, Estonia; 3Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Porto, Portugal Background: Fructose is a hexose sugar largely consumed in the Western diet. It is present naturally in fruits, vegetables and is also used as a sweetener in beverages and candy. Fructose intolerance may cause unspecific abdominal symptoms (pain, bloating, discomfort, flatus and diarrhea due to osmotic load in the small intestine or sugar fermentation by the colonic anaerobic flora) common also to other functional gastrointestinal diseases. Apart from fructose poor/free diet, no medication is available in patients with fructose intolerance. Aim: As the exact clinical manifestations and frequency of fructose intolerance are still poorly understood, we aimed to detect and survey a cohort of subjects with fructose intolerance in our geographical area (Southern Italy), and to set up a programme of dietary reeducation for consistent symptomatic improvement. Methods: Recruited were 74 subjects (M:F = 24:50, mean age ± SD 41.8 ± 14.8 and 41.9 ± 14.9 years, respectively) with ‘‘unspecific’’ gastrointestinal symptoms including abdominal pain a/o discomfort, bloating, diarrhea in which inflammatory, neoplastic, IBS and celiac disease were excluded. H2-Breath Test (BT) (Lactofan, Medimar & Italchimici, Italy) was used to check for H2-

Effect of red pepper on symptoms of irritable bowel syndrome. Preliminary study M. Bortolotti1, S. Porta2 1

Department of Internal Medicine and Gastroenterology, University of Bologna; 2Medical department, SOFAR, Milano, Italy Background: Abdominal pain, that characterizes irritable bowel syndrome (IBS) together with bloating and disordered defecation, is mainly related to a visceral hypersensitivity due to an increase of TRPV1 nociceptive nerve fibres activity. Aim: As capsaicin contained in red pepper is able to desensitize the TRPV1 fibres, we evaluated whether the red pepper oral administration can decrease the symptoms of visceral hypersensitivity in IBS patients. Methods: The study was performed on fifty patients (mean age 44.6 years; 30 males) with IBS diagnosed following Rome II criteria. After a two weeks washout period, 23 patients were planned to receive for 6 weeks randomly and in a double blind manner 4 pills/day, each containing 150 mg of red pepper powder with a coat that dissolves in the colon, and 27 patients placebo. The patients scored each day in a diary the abdominal pain and bloating intensities following the five points Likert scale. The weekly symptom mean scores and the final patient

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S270 subjective evaluation on treatment effectiveness were statistically compared among groups and intra-groups with appropriate tests. Results: Eight patients dropped from the study: six in the red pepper group for abdominal pain and two in the placebo group. In 8 patients the pills were reduced to 2/day, because of abdominal pain at the onset of treatment. The intra-group comparisons showed that the abdominal pain and bloating mean score values of the last weeks of treatment were significantly (p \ 0.05) improved in patients taking red pepper (1.8 ± 0.6 and 2.0 ± 0.8; mean ± SD) with respect to pre-treatment values (2.8 ± 0.8 and 2.7 ± 0.6, respectively; mean ± SD) at variance with patients taking placebo (Fig. 1). In addition the patient subjective evaluation on the effectiveness of red pepper treatment was significantly (p \ 0.05) better than that of placebo (3.8 ± 1.1 and 1.9 ± 1.1, respectively; Fig. 2).

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 considered by the patients more effective than placebo. The only drawback is represented by the temporary occurrence of abdominal pain in the first days of treatment in some patients with the higher dose of capsaicin. We hope that the results of this preliminary research, although with some methodological limitations, may represent a spur to pursue the studies with this kind of treatment based on desensitization of colonic nociceptive TRPV1 neurons, the hyperactivity of which is responsible of abdominal pain in IBS patients, even by using other substances more tolerable and effective than capsaicin.

Obscure gastrointestinal bleeding: single centre experience of capsule endoscopy C. Calabrese, G. Liguori, P. Gionchetti, F. Rizzello, S. Laureti, M. Di Simone, G. Poggioli, M. Campieri Dipartimento di Medicina Clinica, Universita` di Bologna, Bologna, Italy

Fig. 1 Course of the weekly mean abdominal pain intensity scores (mean ± SD) during red pepper (D) and placebo (o) administration. Filled triangles and circles indicate values significantly different from the corresponding baseline (B) values

Background: The advent of video capsule endoscopy (CE) has resulted in a paradigm shift in the approach to the diagnosis and management of patients with obscure gastrointestinal bleed (OGIB). With increasing global availability of this diagnostic tool, it has now become an integral part of the diagnostic algorithm for OGIB in most parts of the world. However there is scant data on optimum timing of CE for maximizing diagnostic yield. OGIB continues to be a challenge because of delay in diagnosis and consequent morbidity and mortality. Aim: To identify optimum timing to maximize diagnostic yield by capsule endoscopy (CE) in patients with obscure gastrointestinal bleeding (OGIB). Methods: We identified patients who underwent CE at our institution from May 2006 to May 2011. Patient medical records were reviewed to determine type of OGIB (occult, overt), CE results and complications, and timing of CE with respect to onset of bleeding. Results: Out of 346 patients investigated for OGIB, 290 (83.8%) had some lesion detected by CE. In 206 patients (59.5%), definite lesions were detected that could unequivocally explain OGIB. Small bowel angiodysplasia, ulcer/erosions secondary to Crohn’s disease, nonsteroidal anti-inflammatory agent use, and neoplasms were the commonest lesions detected. Visualization of entire small bowel was achieved in 311 (89.9%) of cases. Six cases were compromised due to the capsule remaining in the stomach during the entire test, and capsule retention was noted in two patients. Conclusion: in this study CE was proven to be a safe, comfortable, and effective procedure, with a high rate of accuracy for diagnosing OGIB.

Distinct proteomic profiles characterize non erosive from erosive reflux disease Fig. 2 Comparison between the patient subjective evaluation on the therapeutical effectiveness of red pepper treatment against that of placebo (mean ± SD) * = p \ 0.05 Conclusions: The results of this preliminary study seem to indicate that red pepper powder orally administered in IBS patients with enteric-coated pills is significantly more effective than placebo in decreasing the intensity of abdominal pain and bloating and is

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C. Calabrese, V. Marzano, A. Urbani, G. Lazzarini, M.C. Valerii, G. Liguori, F. Rizzello, P. Gionchetti, M. Campieri, E. Spisni Dipartimento di Medina Clinica, Universita` di Bologna, Bologna, Italy Background & Aims: Erosive reflux disease (ERD) and non-erosive reflux disease (NERD) are often regarded as part of the spectrum of

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 the same disease, although some consider them two distinct conditions. Both these variants should be regarded as different disease states and evaluated individually for underlying mechanisms and therapeutic approaches. Different molecular mechanisms may also underlie the development of each clinical type. Existing data on the natural course of each form of reflux disease do not provide convincing evidence of progression from NERD to ERD. Following a proteomic investigation, this study provides a very promising way to elucidate molecular features to characterize NERD and ERD at the protein level. Materials and Methods: A total of 56 consecutive subjects were enrolled: 10 healthy subjects, 24 with NERD and 22 with ERD. Eight specimens were taken from macroscopically normal mucosa at 5 cm of gastroesophageal junction. Four were processed for the proteins extraction and 4 for evaluation by haematoxylin–eosin and immunohistochemistry. We used shotgun proteomics to identify tentative disease molecular features for ERD or NERD. Candidate distinctive proteins were verified by immunohistochemistry. Results: Shotgun proteomics analysis revealed 33 differentially expressed proteins in NERD versus ERD samples, involved in cellular proliferation, keratinization, stress responses and sugar metabolism. Based on a gene ontology meta-analysis, seven of them were further analyzed by western blotting (WB) and four also by immunohistochemistry. We identified novel candidate disease molecular features for GERD and few distinctive proteins to discriminate NERD and ERD. In particular, Transitional Endoplasmic Reticulum ATPase (TER ATPase), GAPDH, Alpha 1 Acid Glycoprotein 1, Annexin A1, Calmodulin and 14-3-3 proteins were confirmed at WB analysis. Conclusion: Cell damage at the microscopic level can progress to macroscopic damages and erosions because of the increasing size of the defect in the epithelial barrier. However, this can be repaired through one of two mechanisms: restitution or regeneration. Regeneration requires cell replication, while restitution uses cell migration to repair barrier defects. The altered expression of several proliferation-related protein, associated with a decreased translocation of Annexin A1 to the cell membrane point out that both regeneration and restitution are impaired in GERD and especially in ERD mucosa. Our analysis clearly reveals the importance of a proteomics approach in identifying candidate biomarkers for GERD diagnosis. This study successfully discloses novel differentially expressed proteins that could become useful for an objective characterization of NERD vs ERD.

Contrast-enhanced ultrasound with sonovue: differentiation between benign and malignant focal liver lesions. Experience of a single center M.L. Cappai, G. Vidili, G. Delitala Department of Clinic Medicine, Sperimental and Oncology, University of Sassari, Sassari, Italy Purpose: the aim of our study was to investigate the ability of contrast-enhanced sonography (CEUS) to differentiate between benign and malignant focal liver lesions. Methods: we prospectively enrolled 249 patients (194 males, 55 females, aged 59 ± 14,3 years) with focal liver lesions not characterizable in conventional ultrasound. After intravenous injection of one or two bolus (2 mL) of ultrasound contrast agent (SonoVue, Bracco), the liver lesion was examined continuously for 5 minutes using contrast-specific software with low mechanical index. All the

S271 lesions characterized as benign were underwent to dimensional ultrasound follow-up every three or six months for at least 24 months of follow up. For the lesions that showed malignant aspect, CT and/or MRI and/or biopsy were performed. CEUS diagnosis was compared with the results of ultrasound follow-up for suspected benign liver lesions and with CT, MRI or biopsy diagnosis for suspected malignant liver lesions. Results: ninety-four patients had malignant focal lesions, including 107 hepatocellular carcinomas, 17 cholangiocellular carcinomas, 52 metastases. One hundred fifty-five patients had benign focal lesions, including 128 regenerative nodules, 116 hemangiomas, 10 focal nodular hyperplasia, 29 focal fatty change areas, 2 necrotic nodules, 5 adenomas, 1 nodular regenerative hyperplasia. CEUS was conclusive (CEUS diagnosis confirmed by other methods) in 98.1% of benign lesions diagnosis and 96.5% of malignant lesions diagnosis. CEUS, in our center, has a sensitivity of 93.8% and a specificity of 97.3% in the differential diagnosis between benign and malignant lesions with a PPV of 95.8% and NPV of 96%. Conclusion: CEUS is useful in the differentiation between benign and malignant focal liver lesions and should be considered as a first diagnostic step for the characterization of lesions detected in conventional ultrasound.

Antibiotic susceptibility patterns in 389 naı¨ve Helicobacter pylori infected patients G. Fiorini1, L. Gatta2, C. Ricci3, V. Castelli1, I. Saracino1, A. Zullo4, D. Vaira1 1

Dipartimento diMedicina Clinica, Universita` di Bologna; Gastroenterology and Endoscopy Unit, Versilia Hospital, Lido di Camaiore; 3Gastroenterology Unit, University of Brescia; 4 Gastroenterology and Digestive Endoscopy ‘‘Nuovo Regina Margherita Hospital’’ Roma, Italy 2

Background: antimicrobial resistant strains of Helicobacter pylori (H. pylori) have been increasing worldwide, and it has been speculated that this may account for progressive decrease in eradication rates reported in the literature. Aim: to assess the prevalence of resistant strains to metronidazole (M), Clarithromycin (C), and Levofloxacin (L) in a cohort of naı¨ve patients performing an EGDS for dyspeptic symptoms in Italy. Methods: 389 H. pylori infected patients (Male: 42.7%; median age: 51 years; IQR: 40 and 64 years) underwent upper endoscopy and a biopsy sample was also obtained to perform culture and an in vitro antimicrobial susceptibility testing. Susceptibility testing was performed by epsilometer test (Etest) and the following MIC breakpoints were used: resistance to C ([1 microgram/ml); resistance to M ([8 microgram/ml), and resistance to L ([1 microgram/ml). Results: data on resistance were available for 368 out of 389 (94.6%) patients. Resistance to M was found in 46.7 % of the strains; to C in 26.3% of the strains; and to L in 23.9% of the strains. Double resistance to C+M was found in 19.6 % of the strains; to C+L in 10.3% of the strains; and to M+L in 16.3 %. 8.1 % of the strains were resistant to M+C+L. Considering resistance to a single antibiotic, resistance to M was more likely to occur in women than men (OR: 2.8; 95% CI: 1.3 to 5.9); considering the double resistance, women were also more likely to have resistance to both C+M than men. Conclusions: prevalence of strains resistant to L in H. pylori infected naı¨ve patients is becoming similar to that of C; treatments including L

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may in future results in the decreasing performance, due to the raise of primary resistance to this antibiotic.

Results: Trend of RSs in patients taking ST Cla-R

Metro-R

Levo-R

Balloon-occluded RFA plus tace: a new combined single-step therapy for treatment of single large hepatocellular carcinoma

50 45

46

Prevalence (%)

40 35 30 29

25

26 24

20 19

15

probably related to a deficit in processing positive feedback within the limbic brain system related with behavioural adaptation. These results had interesting implication on patient’s compliance and therapy adherence.

17

V. Cesario1, R. Iezzi1, M.C. Campanale1, T.A. Di Rienzo1, G. Gigante1, G. Caracciolo1, E. Rinninella1, F.R. Ponziani1, F. Pirro1, B.E. Annicchiarico1, M. Siciliano1,M. Pompili1, G.L. Rapaccini1, L. Riccardi1, M.A. Zocco1, A. Milani1, A.M. De Gaetano1, G.B. Gasbarrini2, L. Bonomo1, A. Gasbarrini1 1

Policlinico Gemelli, Universita` Cattolica Sacro Cuore, Roma; Fondazione Ricerca in Medicina, Bologna, Italy

10

2

5 0 AP&T 2007

DDW 2011

Neural correlates of behavioral adaptation and decision-making in alcohol abusers with and without liver cirrhosis M. Cavalletti, S. Montagnese, A. Gatta, P. Amodio, D. Mapelli, S. Schiff Universita` degli Studi di Padova, Padova, Italy Background: Liver cirrhosis frequently depends by sustained and prolonged alcohol consumption. In general, subjects prone to alcohol misuse show deficits in decision-making. This profile seems to depend on an alteration in the neural mechanisms implicated in behavioral adaptation guided by feedback. The Iowa Gambling Task (IGT) is a card game developed to study economic decision-making based on trial and error. The IGT has been found to be particularly sensitive in detecting individuals with a history of alcohol misuse. Objectives: In the present study the IGT was used to evaluate the neural correlates of feedback evaluation in win and loss trials in a sample of patients affected by cirrhosis and patients with alcohol related problems without cirrhosis. Methods: Twenty healthy controls, twelve patients with exotoxic cirrhosis (without hepatic encephalopathy) and nine patients without liver insufficiency underwent the IGT and PHES battery. IGT performance was defined as the temporal profile (quintiles) of the difference between the numbers of choices from advantageous minus disadvantageous decks. Event-related brain potentials (ERPs) related to feedback presentation were recorded from 31 electrodes. Low Resolution Electromagnetic Tomography Analysis (LORETA) was adopted to localized cerebral differences between controls and patients in the two feedback conditions (win vs. loss). Results: No differences were found in PHES scores between the two groups of patients (p [ .05). Behavioral analysis of IGT scores highlighted a significant interaction between groups and quintiles [F(8.52) = 3.05, p \ .01], confirming a defect in decision-making in patients with alcohol related problems. Planned comparison in the last quintiles revealed no differences in IGT performance between the two group of patients, suggesting that this defect is independent by cirrhosis [p [ .05]. ERPs analysis showed a significant interaction between groups, conditions starting 500-600 ms after feedback onset [F(4.76) = 3,6437, p = 0.009] suggesting a difference in processing positive feedback between groups. LORETA revealed that this difference is related to the activity of the anterior cingulate cortex, parahippocampal and fusiform gyri. Conclusions: Both patients with cirrhosis and alcohol related problem without cirrhosis show a deficit in monetary decision-making,

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Aim: To evaluate the feasibility and safety of combined single-step therapy with balloon-occluded RFA followed by TACE in patients with single unresectable hepatocellular carcinoma larger than 3 cm. Materials & Methods: 10 consecutive patients with single unresectable large HCC (mean diameter 4,43 ± 1,27 cm; range: 3-6.5 cm), not suitable to thermal ablation for site or size of the lesion, were enrolled in our single-center multidisciplinary pilot study. The schedule of treatment consisted of: percutaneous RFA (single 3-cm monopolar needle insertion) of the target lesion during occlusion of the hepatic artery supplying the tumor followed by superselective TACE with epirubicin (Farmorubicin 50 mg Powder) loaded DC Bead. Adverse events as well as intra/periprocedural complications were clinically assessed. Early local efficacy in target lesions in terms of persistence of contrast enhancement and presence of necrotic diameter, was evaluated on 1-month follow-up multiphasic CT basing on m-RECIST criteria. Results: The procedure was feasible in all patients. No major complications occurred. Overall technical success, defined as complete devascularization during the arterial phase of the target lesion, was achieved in 8/10 patients with 2 partial response (persistence of vital tissue less than 30%), with a nonenhancing area corresponding in shape to the previously identified HCC (necrotic diameter: 3-6 cm). Conclusion: Balloon-occluded-RFA plus TACE seems to be a safe and effective combined therapy for the treatment of advanced unresectable single large HCC, allowing to obtain a high complete local response rate also in patients not suitable to thermal ablation for site or size of the lesion.

Balloon-occluded percutaneous RFA as bridge to tace for management of advanced hepatocellular carcinoma with hepatic arteriovenous fistula: a technical innovation V. Cesario1, R. Iezzi1, M.C. Campanale1, T.A. Di Rienzo1, G. Gigante1, E. Rinninella1, F.R. Ponziani1, F. Pirro1, B.E. Annicchiarico1, M. Siciliano1, M. Pompili1, G.L. Rapaccini1, L. Riccardi1, L. Siciliani1, M.A. Zocco1, A. Milani1, A.M. De Gaetano1, G.B. Gasbarrini2, L. Bonomo1, A. Gasbarrini1 1

Policlinico Gemelli Universita` Cattolica Sacro Cuore, Roma; Fondazione Ricerca in Medicina, Bologna, Italy

2

Aim: To evaluate the safety and efficacy of balloon-occluded RFA in the temporary resolution of massive arteriovenous fistula in patients with advanced hepatocellular carcinoma as bridge to safe and effective TACE.

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Materials & Methods: 5 consecutive patients with advanced multinodular (2-6 nodules) unilobar unresectable HCC with a target main lesion larger than 5 cm (mean diameter 8,23 ± 1,87 cm; range: 5,512 cm), not suitable to TACE due to a massive arterio-portal (A-P) fistula, were enrolled in our single-center multidisciplinary pilot study. The schedule of treatment consisted of: percutaneous RFA (single 3-cm monopolar needle insertion) of the hepatic area surrounding the arteriovenous fistula during occlusion of the feeder artery of the arterio-portal shunt. After balloon-occluded RFA, an hepatic arteriography was performed in order to evaluate the disappearance of fistula to subsequently perform a lobar TACE (450 mg carboplatin and lipoidal plus temporary embolization with spongostan). Adverse events as well as intra/periprocedural complications were clinically assessed. Technical success was defined by the immediate results of balloon-occluded RFA in terms of disappearance, reduction or persistence of the A-P shunt. Early local efficacy of TACE was then evaluated on 1-month follow-up multiphasic CT based on m-RECIST criteria. Results: No major complications occurred. Technical success, defined as complete disappearance of fistula, was achieved in all patients, being able to undergo standard TACE. 1-month follow-up CT demonstrated an acceptable lipoidal accumulation ([50%, necrotic diameter: 4-8,5 cm) within therapeutic target area (partial response according to m–RECIST criteria) with persistence of the massive arteriovenous fistula. Conclusion: Our results suggest that balloon-occluded RFA of A-P shunt in patients with advanced HCC can temporary reduce shunting, allowing to perform a safe and therapeutically useful TACE, with a satisfactory control of tumor growth.

diet from at least 12 months with histologically proven mucosal recovery, 2 potential CD patients (PCD) [M/F: 0/2; mean age: 29.5 ± 14.8, range: 13-46] carrying mucosal Marsh 1 lesions and positivity of anti-endomysium antibodies, and 11 healthy controls (HC) [M/F: 5/6; mean age: 61.9 ± 20.7, range: 26-81] suffering from functional dyspepsia. Serum samples were taken from each participant in the study and stored at -20C until needed. IgA-AAA qualitative determination was blindly performed by indirect immunofluorescence on sections containing rat epithelial intestinal cells (Eurospital; Trieste, Italy) according to the manufacturer’s instructions. Briefly, sera were deprived of complement and diluted in a medium containing EDTA to avoid aspecific binding of depolymerizing proteins and recognition of serum proteins able to compete with actin filaments for antibodies’ binding. Sensitivity, specificity and diagnostic accuracy were assessed using conventional formulas. Results: 3/9 UCD (33%) were IgA-AAA positive, whilst the TCD and PCD patients, as well as the HC subjects resulted all negative. Sensitivity was, then, 33% in UCD with a specificity of 0%. In TCD group, in face of a very high specificity (100%), the sensitivity was 0%. Diagnostic accuracy, therefore, was 33% for UCD and 100% for TCD. For both PCD and HC conditions, the same sensitivity, specificity and diagnostic accuracy values as TCD population were observed. Conclusions: In our hands, determination of IgA-AAA does not indicate the presence of an active disease. By consequence, it has little to offer in diagnostic screening for CD when compared to antiendomysium and anti-transglutaminase assays. Histology, therefore, is still necessary to diagnose CD.

Are anti-actin antibodies useful for coeliac disease diagnosis?

Herpes virus-6 chromosomal integration misled the management of Crohn’s disease

R. Ciccocioppo1, M. De Amici2, V. Boccaccio1, M.L. Russo1, A. Gallia1, E. Betti1, V. Imbesi1, G. Zanellati1, G. Cangemi1, G.R. Corazza1 1 Clinica Medica I; 2Laboratorio di Pediatria, Fondazione IRCCS Policlinico San Matteo, Universita` degli Studi di Pavia, Pavia, Italy

Background: Coeliac disease (CD) is an immune-mediated enteropathy caused by gluten ingestion in genetically susceptible individuals in which an increase of mucosal permeability seems to play a crucial role. Gliadin peptides, a component of gluten, have been reported to cause a rapid alteration of the actin cytoskeleton of enterocytes in CD patients. Actin is a globular protein found in either monomeric form, as G-actin, or in filamentous form as F-actin, and each subunit is able to bind to both ATP or ADP. Gliadin rapidly increases actin polymerization leading to rearrangement of actin filaments, especially in the intracellular subcortical compartment. It is likely that these newly generated actin polymers may be exposed to gut-associated lymphatic tissue, causing the production of specific IgA antibodies against actin filaments (IgA-AAA). Previous studies showed that the presence of IgA-AAA correlates with the degree of small intestinal villous atrophy, an hallmark of CD. This may indicate that antibody production depends on mucosal injury as a consequence of the release of actin from apoptotic cells which triggers the autoimmune response. On these basis it has been suggested that detection of IgA-AAA might, in some cases, overcome the need of the intestinal biopsy for diagnostic purpose. Aim: We aimed to evaluate the prevalence and accuracy of IgA-AAA in a cohort of CD patients. Patients and Methods: We enrolled 9 anti-endomysium positive and histologically proven untreated CD patients (UCD) [M/F: 0/9; mean age: 36.7 ± 12.3, range: 10-48], 14 treated CD patients (TCD) [M/F: 5/9; mean age: 36 ± 15.9, range: 6-71] following a strict gluten-free

R. Ciccocioppo1, F. Baldanti2, M.L. Russo1, V. Boccaccio1, A. Gallia1, G. Zanellati1, V. Imbesi1, E. Betti1, G. Cangemi1, C. Alvisi3, L. Chezzi2, F. Viola4, M. Aloi4, S. Cucchiara4, G.R. Corazza1 1 Clinica Medica I; 2SS Virologia Molecolare, SC Virologia e Microbiologia; 3Endoscopia Digestiva; Fondazione IRCCS Policlinico San Matteo, Universita` degli Studi di Pavia; 4Clinica Pediatrica; Policlinico Umberto I, Universita` degli Studi di Roma, Roma, Italy

Background: In an era of increasing use of immunosuppressive and biological therapies, opportunistic infections have emerged as a crucial safety issue in patients with chronic inflammatory conditions. Crohn’s disease (CD) is an inflammatory bowel disease in which antitumor necrosis factor-a antagonists have emerged as first line treatment mainly in those patients with the fistulizing behaviour. The risk for re-activation of latent viral infections is, therefore, relevant. Besides Cytomegalovirus and Epstein Barr virus, the remaining members of the human herpes virus (HHV) family are also considered major opportunistic viral agents in immunocompromised patients. In fact, two cases of encephalitis in patients with inflammatory bowel disease on azathioprine therapy have already been described. As far as HHV-6 is concerned, this is a ubiquitous DNA b-herpesvirus most probably transmitted through saliva during early childhood, which establishes latency in immune cells. Its potential pathogenic role in CD has already been investigated in terms of positive cells and viral load on mucosal specimens, and no difference with respect to the control group was found. Moreover, it has recently been shown that persistently high peripheral blood HHV-6 DNA levels might be the expression of quiescent virus chromosomal integration instead of virus reactivation.

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S274 Aim: Herein, we report on the mistreatment of a 16-year-old girl suffering from refractory fistulizing perianal CD who experienced progression of the disease due to discontinuation of the immune suppressive therapy for a supposed HHV-6 reactivation. Patients and Methods: She was diagnosed as having a disseminated HHV-6 disease because of fever, fatigue, diarrhea and weight loss unresponsive to anti-tumor necrosis factor-a antagonist (Adalimumab) given for the primary disease, and the presence of high HHV-6 DNA levels in the blood (mean 240.000 copies/ml). Two fulldosage courses of antiviral therapy (ganciclovir for 2 weeks, then valganciclovir for 3 weeks) with a concomitant discontinuation of the biological therapy for 12 weeks proved ineffective in reducing HHV6 DNA serum levels and, in turn, caused a severe flare up of the underlying disease. The patient was, then, referred to the Department of Internal Medicine of the Fondazione IRCCS Policlinico San Matteo as a possible candidate for compassionate use of autologous bone marrow-derived mesenchymal stromal cells as regenerative therapy (Bio-Ethics Committee, procedure n. P-20090001513), since the persistently high levels of circulating HHV-6 DNA discouraged the use of immunosuppressive and/or biological therapy. Screening for opportunistic infections was carried out on specimens from different tissues by means of quantitative real-time Polymerase Chain Reaction. Results: Quantification of HHV-6 genome in both blood and colonic mucosal samples confirmed the presence of high levels of HHV-6 DNA, however, when adjusting the HHV-6 DNA load per cell, a constant amount (171,193 copies/105 cells) was found. Following the hypothesis of HHV-6 chromosomal integration (recently reported in bone marrow transplant recipients), the search for HHV-6 DNA was carried out those cells not involved in virus active replication, such as hair follicles. Indeed, a high viral DNA load, comparable with that observed in the blood cells and intestinal mucosa, was found thus confirming the hypothesis of chromosomal integration, and indicating inheritance through the germ line. Antiviral treatment was then stopped, and the biological agent was re-introduced (adalimubab, 80/40 mg first two doses, then 40 mg every two weeks), together with total parenteral nutrition, with a rapid improvement of the patient’s clinical condition. Conclusions: In conclusion, this report is intended to warn clinicians against misinterpretation of virological surrogate markers, and suggests a multidisciplinary evaluation of immunosuppressed patients to avoid inappropriate therapeutic approaches.

Reactivation of opportunistic viral infections in inflammatory bowel disease R. Ciccocioppo1, F. Baldanti2, G. Zanellati1, V. Boccaccio1, M.L. Russo1, V. Imbesi1, A. Gallia1, E. Betti1, G. Cangemi1, E. Strada3, G.R. Corazza1 Clinica Medica I; 2SS Virologia Molecolare, SC Virologia e Microbiologia; 3Endoscopia Digestiva, Fondazione IRCCS Policlinico San Matteo, Universita` degli Studi di Pavia; Pavia, Italy 1

Background: Infectious manifestations represent an important cause of morbidity and, seldom, of mortality in inflammatory bowel disease (IBD). The risk for infections may be related to the disease process itself, its complications and/or to the use of immunosuppressive and biological medications. Indeed, steroids, immunosuppressive agents, such as azathioprine, 6-mercaptopurine, cyclosporine, and biological agents, i.e., tumor necrosis factor-a antagonists, inhibit immune system through different pathways, thus predisposing patients to

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 reactivation of latent viral infections. Among these, Herpesviridae species, especially cytomegalovirus (CMV) and Epstein-Barr virus (EBV) may cause active disease in immunosuppressed patients, whereas they ordinarily would cause mild or no disease in immunocompetent hosts. When viral reactivation involves gastrointestinal tract, the clinical picture mimics a relapse of IBD, thus it is hard to distinguish between them. Polymerase chain reaction (PCR) assay has emerged as the most sensitive method for diagnosis of CMV and EBV infection in transplanted patients, but it is still rarely applied in the gastroenterology area. Aim: We aimed, therefore, to investigate the prevalence and the role of reactivation of CMV and EBV latent infections in a group of IBD patients refractory to immunosuppressive and/or biological agents by using PCR analysis on both blood and mucosal samples. Patients and Methods: We enrolled 25 IBD patients (M/F: 14/11; mean age: 42.9 ± 15 years, range 16-68), of which 9 suffering from Crohn’s disease (CD), 15 from ulcerative colitis (UC) and one having indeterminate colitis (IC). Among them 12 (8 UC, 3 CD, 1 IC) were considered refractory because of the persistence of serological, endoscopic and clinical indexes of disease activity despite of an immunosuppressive and/or biological treatment. Eleven sex/age matched healthy subjects suffering from irritable bowel syndrome (HC) were also recruited. Whole blood samples and perendoscopic colonic biopsies, routinely taken from all tracts, were obtained from each participant. DNA was extracted from each sample and quantitative realtime PCR analysis for CMV and EBV genome was performed. All viral DNA results were expressed as copies normalized to 105 cells. A cut-off value of 103 copies/105 cells was established to distinguish a strong positivity from a weak positivity for the analysis of mucosal data. Statistical comparisons between mean values were performed using the Mann-Whitney U test for non-parametric data and a p \ 0.05 was considered statistically significant. Results: In the group of refractory IBD patients, we found 6/12 strong positivity for EBV, 3/12 for CMV, and 3/12 for both viruses in mucosal samples, with a grading from the caecum to the rectum where we found the highest values. EBV-DNA values ranged from 78 to 966,333, and CMV-DNA from 286 to 221,697 copies/105 cells, with a statistical difference in comparison to the mean values found in both non-refractory IBD and HC of p = 0.3 and 0.006 for CMV, respectively, and 0.0001 for EBV with respect to non-refractory IBD. As regards blood viral load, EBV-DNA was found in 4 refractory IBD patients, CMV-DNA in one, and both viruses in another patient. EBV-DNA amounts ranged from 400 to 50,700, while CMV-DNA from 300 to 32,200 copies/105 cells. In the group of non-refractory IBD patients, we found a weak mucosal positivity for CMV in 4 patients and for EBV in 3, with blood search resulting always negative. In this group, EBV-DNA ranged from 27 to 894, and CMVDNA from 14 to 273 copies/105 cells. Finally, none in the HC group showed any positivity in mucosa and/or blood. The establishment of antiviral therapy with ganciclovir (250 mg i.v. twice a day for 3 weeks) leads to a resolution of clinical picture in those patients with CMV active infection, while discontinuation of the immunosuppressive agents in the cases of EBV disease determined only a transient amelioration of clinical conditions. Conclusions: Our data show that CMV and EBV reactivation may represent a cause of ‘false’ refractoriness to immunosuppressive or biological therapy in IBD. In view of the increasing use of more aggressive treatment, we strongly support the need for an appropriate screening for opportunistic viral reactivation in every immunosuppressed patient in order to optimize their therapeutic management.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 The receptor for the advanced glycation end products is overexpressed in the intestinal mucosa of patients with Crohn’s disease R. Ciccocioppo1, V. Boccaccio1, M.L. Russo1, A. Gallia1, E. Betti1, V. Imbesi1, G. Zanellati1, G. Cangemi1, C. Alvisi2, R. Desio3, A. Rossi3, G.R. Corazza1

S275 Conclusions: Our study provides the first evidence of an overexpression of RAGE on intestinal mucosa in CD patients. The significant inverse correlation with sRAGE and the positive correlation with CRP suggests the possible involvement of RAGE in the pathogenesis of this chronic enteropathy.

1

Clinica Medica I; 2Endoscopia Digestiva, Fondazione IRCCS Policlinico San Matteo; 3Dipartimento di Biochimica ‘‘A. Castellani’’, Universita` degli Studi di Pavia, Pavia, Italy Background: Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory and disabling enteropathies whose aetiology is still not fully understood. The receptor for advanced glycation end products (RAGE) is a transmembrane multiligand receptor that belongs to the immunoglobulin superfamily and is expressed at low levels in multiple tissues. Upon its activation by several classes of ligands during both innate and adaptive immune responses, RAGE triggers intracellular signals which ultimately lead to the maintenance of a sustained inflammation. Up to date, an upregulation of RAGE expression has been found in several chronic inflammatory and degenerative diseases, such as rheumatoid arthritis, diabetes mellitus, atherosclerosis, cancer and neurodegenerative conditions. The cleavage of its extracellular domain by matrix metalloproteinases causes the release of its soluble form (sRAGE) which plays a protective role thanks to the ability to capture and block RAGE ligands. Despite the recent evidence of an increased expression of S100A12 calgranulin, a ligand of RAGE, in inflamed intestinal mucosa of CD and UC patients, no data on RAGE expression have been collected yet. Aim: We investigated RAGE mucosal expression and its correlation with clinical and serological indexes of disease activity, as well as with sRAGE serum levels, in a cohort of CD and UC patients. Patients and Methods: We enrolled 11 patients with CD (M/F: 1/10; mean age: 35.3 ± 11.8), 8 with UC (M/F: 6/2; mean age: 43.7 years ± 17.1), and 5 sex/age matched healthy controls (HC) [M/F: 2/3; mean age: 55.7 ± 10.1] suffering with irritable bowel syndrome. Clinical activity was assessed by CD activity index (CDAI) in CD patients and Simple Index (SI) in UC patients. Body mass index and blood levels of C reactive protein (CRP) and erythro-sedimentation rate (ESR) were also determined. Serum samples and multiple ileal and/or colonic biopsies were taken from both apparently inflamed and normal mucosa in CD and UC patients, and from normal mucosa in HC subjects, and immediately frozen until required. RAGE expression was determined on mucosal samples by means of Western Blotting using a polyclonal anti-human RAGE IgG antibody (R&D System, Minneapolis, MN, USA) previously tested on CACO-2 cells, and the results were normalized for b-actin. Densitometric analysis of Western Blotting sheets was then performed (Versadoc model 3000; Biorad Laboratories, California, USA). Serum levels of sRAGE were quantified by ELISA by using the Quantikine Human RAGE Immunoassay (R&D System). Statistical comparisons between mean values were performed with the Mann-Whitney U test for nonparametric data. Correlations were searched by applying the Spearman rank correlation test. A level of p less than 0.05 was considered statistically significant. Results: RAGE expression was significantly higher in CD patients as compared to UC patients (p = 0.002) and to HC (p = 0.008), without any appreciable difference between normal and inflamed mucosal areas. A significant inverse correlation was found between RAGE expression and sRAGE levels in CD (p = 0.03, r = -0.65) and UC patients (p = 0.004, r = -0.9), as well as in HC (p = 0.01, r = -1.0). Moreover, in CD patients RAGE expression significantly correlated with CRP levels (p = 0.047, r = 0.8) whilst no correlation with ESR, body mass index and CDAI was found.

Interferon therapy for chronic hepatitis virus C infection is not associated to an increased risk to develop coeliac disease R. Ciccocioppo1, G.A. Piccillo2, V. Boccaccio1, G. Bertino3, S. Neri3, A. Ardiri3, P.M. Boemi4, M.L. Russo1, A. Gallia1, V. Imbesi1, G. Zanellati1, E.G.M. Mondati3, G.R. Corazza1 1 Clinica Medica I, IRCCS Policlinico San Matteo, Universita` di Pavia, Pavia; 2Medicina d’Urgenza, Ospedale Cannizzaro, Catania; 3 Dip. Medicina Interna e Patologie Sistemiche, Universita` di Catania, Catania; 4Medicina Interna, Ospedale Cardinal Massaia, Asti, Italy

Background: Treatment of hepatitis C virus (HCV) chronic infection is based on a combination of an antiviral agent, ribavirin, and a potent cytokine, interferon (IFN)-a, in its pegylated formulation. The immunomodulatory action of IFN-a results in a transduction of a systemic and persistent T helper 1 (Th1) response. Its therapeutic use, therefore, may worsen pre-existing autoimmune diseases, unmask silent autoimmune processes, or even induce de novo autoimmune responses. Some investigators have suggested a possible relationship between HCV treatment and the onset of coeliac disease (CD), an autoimmune enteropathy in which a dysregulated Th1 response towards gluten antigens leads to mucosal damage in genetically susceptible individuals. To date, several studies and case-reports enlightened this event, but exhaustive analyses have not been performed yet. The hallmark of CD is the presence of specific autoantibodies, i.e., anti-endomysium (AEA) and anti-transglutaminase (tTG), and the gold standard for the diagnosis is the presence of a variable degree of villous atrophy with an inflammatory infiltrate of the small bowel mucosa. Clinical picture and laboratory findings range from apparently asymptomatic patients to a global malabsorption syndrome. Aim: We aimed to investigate whether patients with HCV-related liver disease under IFN-a therapy are at major risk to develop CD. Patients and Methods: We enrolled 101 patients suffering from chronic HCV hepatitis (M/F: 63/38; mean age: 57.7 ± 7.4), all naı¨ve and with detectable levels of circulating HCV-RNA which belonged to the 1b genotype (97/101: 96%) or to the 2a/3a one (4/101: 4%). 31 patients were treated with pegIFN a-2a (one subcutaneous administration/week) and ribavirin (1000 mg/die per os) for 12 months, while 70 were not candidates for therapy because of important co-morbidities or because they refused therapy. All patients underwent echo-supported liver biopsy (Menghini method) with histological evaluation based on Scheuer’s score. Serum samples were obtained from all participants in the study at the beginning and after 3, 6, 9 and 12 months, and stored at -20C until required. The following tests were carried out on all samples: thyroid hormones, auto-antibodies (ANA, ENA, AMA, SMA, LKM-1, thyroglobulin, thyroid peroxidase), and the screening for CD through detection of anti-tTG class IgA and IgG antibodies by using an enzyme linked immunoadsorbent assay (Eu-tTG, Eurospital, Trieste, Italy), and AEA by indirect immunofluorescence on sections of monkey esophagus (Antiendomysium IgA, Eurospital, Trieste, Italy). Those patients with clinical and/or serologic features of CD underwent upper endoscopy with multiple duodenal biopsies, and HLA characterisation. To evaluate the risk for CD onset in the two

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S276 groups of IFN-a-treated and untreated patients, determination and comparison of the binomial exact 95% confidence intervals and odds ratios were applied for statistical purpose. Results: Liver biopsy showed a slight to moderate chronic hepatitis at histological examination in all cases, but 8 patients (5 treated/3 untreated) who showed an overt cirrhosis. Child-Pugh classification was applied and all patients scored into class A. The systemic autoimmune screening resulted negative in all the 101 patients enrolled, while 35/70 untreated patients resulted positive for thyroid autoantibodies. None carried IgA deficiency or developed any adverse event which needed therapy withdrawal. Serological screening for CD carried out before, during and at the end of the 12 months of combination therapy resulted always negative. Among the 70 untreated patients, only one showed positivity for IgG anti-tTG since the first determination to the end of the follow up period, with negative AEA, and without any gastrointestinal or systemic symptoms and/or signs suggestive for CD. This patient underwent upper endoscopy and histological evaluation of duodenal biopsies without evidence of mucosal damage. Finally, the search for HLA haplotype associated to CD didn’t show any predisposing condition. The statistical analysis demonstrated the absence of an increased risk to develop CD in the group treated with IFN-a with respect to the untreated. Conclusions: In our cohort of HCV-patients, PegIFN therapy is not associated to the onset of CD. The positivity for IgG anti-tTG found in a patient of the untreated group may be considered an epiphenomenon of the over-expression of this enzyme during liver damage.

Recognizable intestinal motor abnormalities in patients with severe digestive symptoms R.F. Cogliandro, V. Gabusi, C. Frisoni, A. Antonucci, R. De Giorgio, G. Barbara, R. Corinaldesi, V. Stanghellini Department Clinical Medicine, University of Bologna, Bologna, Italy Background: Patients with unexplained recurrent abdominal pain resembling subocclusive episodes who undergo repeated and useless surgical procedures complicated by prolonged postoperative ileus and progressive deterioration of digestive functions are likely affected by chronic idiopathic intestinal pseudo-obstruction (CIIP). Small bowel motor abnormalities are likely responsible of the clinical picture in CIIP, but small bowel motility in patients with other severe digestive syndromes remain poorly characterized. The present study compared clinical features and small bowel motility in patients with severe gastrointestinal functional disorders with (CIIP) and without (SFGID) subocclusive episodes. Methods: We enrolled 70 patients with CIIP and 145 patients with SFGID consecutively referred to the Laboratory of Functional Gastrointestinal Disorders of the S. Orsola-Malpighi Hospital - University of Bologna to undergo a small bowel stationary manometric test. Relevant issues of health status were recorded for each patient according to pre-defined, validated questionnaires at entry. Patients with SFGID were further divided into two groups according to presence or absence of malnutrition: 110 malnourished SFGID (BMI 17.8 ± 1.8 kg/m2) and 35 non-malnourished SFGID (BMI 22.8 ± 3.6 kg/m2). Results: Abnormal motor patterns were recorded in 69 CIIP patients (98.6%), 85 malnourished SFGID patients (74.5%) and 23 non malnourished patients (65.7%). CIIP patients presented more frequently abnormal activity fronts, lack of response to feeding and hypomotility than malnourished and non malnourished SFGID patients: respectively 61.4% vs 42.7% and 31.4%, p \ 0.05 only vs non malnourished FGID; 8.6% vs 0.9% and 2.9%; 21.4% vs 0.9% and 0, p \ 0.05.

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Conclusions: SFGIDs are frequently associated with small bowel motor abnormalities. Motor patterns suggestive of intrinsic neuropathy present the same distribution in patients with CIIP and malnourished SFGID; manometric pattern suggestive of extrinsic neuropathy or hypomotility are significantly more frequent in patients with CIIP.

A case of recurrent abdominal pain F. Costanzo1, G. Carnevale Maffe`1, D. Grataroli1, G. Bergamaschi1, M. Girino2, P. Formagnana1, G.R Corazza1 1

First Department of Medicine, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy; 2Department of Internal Medicine Ospedale Santo Spirito, Casale Monferrato, Italy A 58-year-old man was admitted to our Department for abdominal pain and a suspect of inflammatory bowel disease. His previous history included vascular disease (acute myocardial infarction 7 years earlier) associated to thrombophilia (hyperlipidemia and hyperhomocysteinemia with the C677T MTHFR mutation). Nine months earlier he had been seen at a Surgery Department because of acute abdominal pain. An abdominal CT scan revealed a distended jejunoileal loop in the absence of contrast opacization of a segment of the superior mesenteric artery. A diagnostic laparoscopy, converted to laparotomy during the procedure, did not show any abdominal mass or intestinal obstruction. A selective arteriography showed occlusion of an ileal branch of the superior mesenteric artery, well compensated by collateral circles. Chronic intestinal ischemia was diagnosed and the patient was transferred to an Internal Medicine Ward. Total parenteral nutrition was started together with anticoagulation and double antiaggregation. The clinical course was complicated by relapsing sepsis, with no significant changes in abdominal symptomatology; an angio-CT scan and an NMR confirmed the diagnosis of chronic intestinal ischemia, but the possibility of Crohn’s disease was also suggested. On admission to our Department the patient complained of abdominal pain with distension. An abdominal radiography and ultrasonography were compatible with abdominal obstruction, but there was passage of gas. Ultrasound scans of the ileum also showed a marked wall thickening with increased intraparietal vascularization. However the first-level investigation was suggestive for ischemic findings, the patient was again subjected to second-level investigations (CTabdomen + angio-CT, colonoscopy) which confirmed the presence of known vascular disease of the bowel. The patient resumed oral nutrition and was discharged with only mild improvement of symptoms. Two weeks later abdominal obstruction recurred and, following readmission to our Institution, the patient underwent open laparotomy with resection of an abdominal mass which included 60 cm of distal ileum and 10 cm of ascending colon. Resected bowel contained multiple strictures and distended segments, with thickening of the intestinal wall and adhesions; histological examination suggested that the nature of pathological findings was ischemic. Following surgery, the patient recovered with rapid normalization of his nutritional status. Conclusions: This case shows how the diagnosis of chronic intestinal ischemia was already evident on the basis of clinical course and initial non-invasive investigations, including the ultrasonography of bowel loops, on admission to our department. Further confirmation of the diagnosis of ischemia by second level investigations, although apparently appropriate, markedly delayed the resolution of the case (a total of more than 12 months after first admission), increasing costs and risks to the patient.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 The diagnosis of gallbladder carcinoma: role of contrast enhanced ultrasonography (CEUS) P. de Bonfils1, V.O. Palmieri1, F. Minerva1, M. Barberio1, G. Davanzante1, A. Margari2, G. Palasciano1 Internal Medicine ‘‘A. Murri’’; 2General Surgery ‘‘G. Marinaccio’’, University of Bari, Italy 1

Background: gallbladder cancer is the fifth most common gastrointestinal tumor. It occurs in three per 100,000 people in the United States and is more common in the elderly and in women. Well- to moderately differentiated adenocarcinoma accounts for the most common form of gallbladder carcinoma. Predisposing risk factors include cholelithiasis, chronic biliary infections (Opisthorchis viverrini, Salmonella typhi), primary sclerosing cholangitis, and porcelain gallbladder. The exact pathogenesis remains unclear, although pooling of carcinogens in conditions causing biliary stasis or malignant degeneration of metaplastic changes after chronic inflammation are suggested mechanisms. The clinical presentation is not specific and may include abdominal pain, weight loss, fever, and jaundice, any of which can be seen in cholecystitis and other benign gallbladder conditions as well as in other abdominal malignancies (1). Case report: B.A. 71 years old, came to the ER and was hospitalized in a surgical clinic, because she had acute cholecystitis. The ultrasonography performed in the ER showed light relaxation of the gallbladder, thick and calcified walls and stones inside. The day after, she had a contrast-enhanced ultrasonography in our department which showed a normal volume gallbladder with an irregular external profile. The gallbladder wall was penetrated by an ipoechoic solid formation 23 mm diameter in continuity with the wall. The hollow was reduced and occupied by a lot of stones. After the contrast administration, there was a homogeneous contrast distribution in the wall and in the solid formation for all the exam duration. The diagnostic conclusion was for a possible carcinoma of the gallbladder. After two days, a CT indicated gallstones and irregularly thick walls. The week after, the patient underwent laparoscopic cholecystectomy. The histological exam showed a thick wall gallbladder with a strong grey 2.5 cm solid mass. Histology showed a gallbladder well-differentiated adenocarcinoma with vascular invasion and intratumoral calcification; the carcinoma invaded the whole gallbladder up the surgical resection margin in the neck and the hepatic tissue on the opposite side. Discussion: Conventional ultrasound (US) is the first-line imaging investigation for biliary diseases. Although US has a relatively high sensitivity for the detection of tumor at advanced stages, it is limited in the diagnosis of early lesions and is unreliable for staging. Therefore, CT and, increasingly, MRI are more widely used for further characterization of potentially malignant gallbladder lesions and metastatic survey. Gallbladder carcinoma may appear at any of these imaging techniques as a mass completely occupying or replacing the gallbladder lumen, focal or diffuse asymmetric gallbladder wall thickening, or an intraluminal polypoid lesion. (1). The use of contrast-enhanced ultrasonography (CEUS) has reached the field of bile duct disease in recent years and promising results have been achieved. On conventional US, a solid mass that occupies the whole gallbladder, a sessile polypoid mass, focal or diffuse wall thickening, intralesional hypervascularity or infiltration to adjacent liver may be found. On CEUS, branch-like flow pattern or hyper-enhancement during the early phase is always recognized. On the other hand, washout of the contrast agent within 35-60 s after contrast agent administration occurs in most gallbladder carcinomas, which seems to be a useful clue for differentiation between malignant and benign gallbladder diseases (2). In the presented clinical case, CEUS has

S277 been crucial for the diagnosis showing the tumor better than CT. We suggest that in selected patients, CEUS has to be performed for the diagnosis of gallbladder carcinoma when US and CT are not conclusive. References 1. AJR Am J Roentgenol. 2008 Nov;191(5):1440–7 2. World J Radiol. 2009 Dec 31;1(1):37–44

An unusual cause of iron deficiency anemia G. De Matteis, G. Marrone, C. Cefalo, S. Racco, M.A. Nicolazzi, L. Matarazzo, L. Miele, M. Riccioni, C. Coco, A. Grieco, R. Landolfi Istituto di Medicina Interna, Dipartimento di Medicina Interna e Scienze Mediche Specialistiche, Universita` Cattolica del Sacro Cuore, Roma, Italy A 80-year-old Caucasian female with a past medical history of hypertension, bronchial asthma and mixed anxiety-depression syndrome was referred to our department because of severe anaemia. There was no history of hematochezia, hematemesis, fevers, or trauma. She had a 2 month history of worsening shortness of breath, constant fatigue, dyspeptic symptoms, nausea, weight loss and lack of appetite associated with entomophobia. Physical examination showed pale skin. The complete blood count (CBC) revealed hemoglobin 5.1 (normal female, 12-15 g/dl), MCV 64.7 fl (normal, 81 to 99 fl). The blood biochemistry showed serum iron 12 mcg/dl (normal, 40-150 mcg/dl), serum ferritin level 5 ng/ml (normal, 12-300 ng/ml), transferring saturation 463 mg/dl (normal, 220-360 mg/dl) while other parameters were within normal range. A CBC and the blood biochemistry performed one year earlier were normal. The report of CBC and the blood biochemistry revealed an iron deficiency anemia. In a postmenopausal women with iron deficiency anemia we had to consider the possibility of a chronic gastrointestinal bleeding due to certain types of cancer (esophagus, stomach, colon), esophageal varices, peptic ulcer disease. We considered also a poor absorption of iron in the diet but the patient wasn’t a strict vegetarian and hadn’t a history of gastric bypass surgery. Furthermore, she hadn’t been using antacids, aspirin or nonsteroidal anti-inflammatory medications for a long time. The fecal occult blood test was doubtful. CEA and CA 19-9 were in the normal range. Chest X-rays and abdominal ultrasonography (US) were normal. The upper gastrointestinal endoscopy revealed hiatal hernia and a polyp from the gastric fundus and another from the antrum. At colonoscopy no relief of inflammation, rare diverticula and dolichocolon. As the endoscopy studies had not shown signs of bleeding nor lesions, a video capsule endoscopy (VCE) was performed, which showed ulcerated lesion compatible with suspected small bowel cancer. Abdominal computed tomography (CT) was performed to characterize this lesion showing a multifocal hypervascular bowel tumor. After an initial phase of medical management with the objective of correcting the anemia (blood transfusions, iron supplements i.v.), few days later, the patient underwent laparotomy with complete resection of lesions identified on CT. During this surgical procedure a fuhrer nodule (2 cm) was identified and detected on the gastric fundus. The patient had an uneventful postoperative course and was discharged on the fifth postoperative day. Final histopathological examination of the first detected ileum lesion showed a neuroendocrine tumor with a size less than 1 cm and a localization within the muscular layer. The second detected ileum lesion showed a low mitotic activity (\2 9 50 mitoses HPF), mixed cells of both spindle and epithelioid types (pleomorphic) and a size of

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S278 5 cm, defining a borderline GIST. The resected gastric lesion revealed a mesenchymal tumour categorized as gastrointestinal stromal tumor (GIST), spindle cell type, with low mitotic activity (\2 9 50 HPF) and a size of 2 cm, classified the tumor as ‘‘benign’’. In the our peculiar patient the final diagnosis was iron deficiency anemia caused by ulcerated lesion in a patient with synchronous multiple primary sporadic GIST and neuroendocrine tumor. GIST are commonly regarded as solitary tumors. The occurrence of multiple lesions is considered an extraordinary event restricted to pediatric GISTs and rare hereditary conditions. Complete surgical resection is the treatment of choice for primary GISTs that have not metastasized, even with current advances in molecular targeting therapy with imatinib and sunitinib [1, 2]. References 1. H. Joensuu, C. Fletcher, S. Dimitrijevic, S. Silberman, P. Roberts, G. Demetri. Management of malignant gastrointestinal stromal tumours. Lancet Oncol. 2002;3:655–664 2. Gasparotto D, Rossi S, Bearzi I, Doglioni C, Marzotto A, Hornick JL, Grizzo A, Sartor C, Mandolesi A, Sciot R, et al. Multiple primary sporadic gastrointestinal stromal tumors in the adult: an underestimated entity. Clin Cancer Res. 2008;14:5715–5721

Hepatic encephalopathy: difficulties sleeping or difficulties staying awake? M. De Rui, S. Schiff, D. Aprile, E. Balistreri, I.D. Raduazzo, P. Angeli, A. Gatta, P. Amodio, S. Montagnese Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy The relationship between hepatic encephalopathy (HE) and sleepwake alterations remains debated. Recent data suggest that in patients with cirrhosis neuropsychiatric impairment might be associated with excessive daytime sleepiness, while insomnia may have a different pathophysiology. The aim of this study was to investigate the relationship between sleep-wake complaints and neuropsychiatric status at baseline and during follow-up in a well-characterised group of patients with cirrhosis. One hundred and six consecutive outpatients with cirrhosis were enrolled [mean ± SD age: 57 ± 11 yrs, 77 (73%) males, Child’s class A:36, B:49 and C:21; portal-systemic shunt documented in 50 out of 69 investigated (72%)]. Patients were asked to answer yes/no to three questions investigating the presence of excessive daytime sleepiness, difficulty falling asleep and frequent night awakenings in everyday life. All underwent formal neuropsychiatric assessment, EEG recording and paper-and-pencil psychometry (PHES). The EEG was analyzed spectrally and psychometric tests scored according to age/education-adjusted Italian norms. Fifty-eight patients were followed up prospectively for an average of 8 ± 6 months, in relation to the occurrence of death/ transplantation and HE-related hospitalisations. On the day of study, 37 patients (35%) had mild overt HE, 33 (31%) minimal HE (normal clinically, abnormal PHES and/or EEG), while the remaining 36 (34%) were unimpaired. Seventy-five (72%) patients reported excessive daytime sleepiness, 38 (36%) difficulty falling asleep and 53 (50%) frequent night awakenings. No association was observed between increased sleep latency/night awakenings and indices of neuropsychiatric dysfunction. In contrast, patients complaining of daytime sleepiness had slower EEGs than their counterparts with no difficulties staying awake (EEG dominant frequency 9.3 ± 2.4 vs. 10.1 ± 2.2 Hz, p = 0.05) and excessive daytime sleepiness was also associated with the presence of portal-systemic shunt (Pearson v2 = 3.5, p \ 0.05). During follow-up, four patients died, 9

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 underwent OLTx and 14 had an HE-related hospitalisation. Excessive daytime sleepiness at baseline was associated with the subsequent occurrence of HE-related hospitalisations (p \ 0.05). In conclusion, excessive daytime sleepiness is associated with HE and its development over time, supporting the interpretation of HE as a vigilance defect.

Chronic hepatitis C-autoimmune hepatitis overlap syndrome: not always a therapeutical dilemma A. De Vincentis, G. Galati, U. Vespasiani Gentilucci, C. Mazzarelli, P. Gallo, A. Soriano, A. Afeltra, A. Picardi Campus Bio-Medico, Roma, Italy Case report: We describe a case of a 72-years-old woman who was referred to our center on September 2010 with the diagnosis of chronic hepatitis C (HCV) discovered 10 years earlier. She reported no history of blood transfusion, intravenous drug abuse, tattoos or excessive alcohol consumption. No antiviral treatment was given since that time because a concomitant relief of high titer of autoantibodies and serum IgG levels, arising the question of a coexistent autoimmune hepatitis. By the time of presentation the patient was asymptomatic and physical examination showed a firm, nontender liver edge 3 cm below the right costal margin without splenomegaly, ascites or other signs of clearly advanced liver disease. Her daily medications included 900 mg of ursodeoxycholic acid and 10 mg of olmesartan for a mild arterial hypertension. Laboratory tests showed increased serum levels of transaminases (AST 165 U/L, ALT 273 U/L), normal values of gamma-GT, alkaline phosphatase and bilirubin, good renal function and a moderate reduction of platelet count (99.000/lL). Serum-protein electrophoresis evidenced polyclonal hypergammaglobulinemia (32%) and analysis of autoimmune markers confirmed elevated IgG levels (28 g/L) and strongly positive titer of anti liver-kidney microsomal antibody (1:1280) and antinuclear antibody (1:160). Serum a-fetoprotein level was in the normal range. Viral genotyping showed a HCV-genotype 2a/2c with high viral load (1300000 UI/ml). An abdominal ultrasonography evidenced signs of chronic hepatitis with normal portal vein diameter, normal spleen volume (33 cm2) and multiple, hilar and paraaortic lymphoadenomegalies. Diagnostic hypothesis: Chronic hepatitis C-autoimmune hepatitis Overlap Syndrome (HCV/AIH). Diagnostic deepening: A US-guided liver biopsy was performed. It showed chronic hepatitis with inflammatory cell infiltrates in the portal space with marked interface activity, intralobular plasma cell infiltration and advanced stage of fibrosis (Knodell score: grade 13, stage 3). Histological features supported the clinical hypothesis, although signs of viral damage were prevalent. We referred to the International Diagnostic Scoring System for the Autoimmune Hepatitis, but the final score suggested a probable diagnosis (score 13) because a negative score (-3) related to HCV infection. Decision-making: HCV/AIH is an uncommon condition and, to date, only few cases can be found in literature. Because of antithetical therapeutic options for HCV and AIH, an appropriate therapy remains a dilemma: treatment of HCV with interferon (IFN) may exacerbate autoimmune liver disease, conversely corticosteroids and immunosuppressive therapy for AIH may enhance HCV replication. Up to now, some case series have underlined the efficacy of immunosuppressant drugs in the majority of patients. In our case, instead, favourable HCV-genotype, prevalent viral damage on histology and good clinical conditions drove us to consider treatment with peg-IFN plus ribavirin. Treatment: A 24-weeks-treatment with peg-interferon-alpha2a 180 mcg/week and ribavirin 1000 mg/day was started. After 4 weeks a complete biochemical response (ALT 31 U/L, AST 29 U/L) and

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 a rapid virological response (HCV RNA \15 UI/mL) was seen. However the patient experienced severe haematological adverse effect, so that we were forced to indicate a short suspension of the treatment for severe anemization (hemoglobin 7,3 g/dL). Despite this, antiviral therapy is still ongoing with haematological growth factor support and on-treatment response. Discussion: Considering rapid virological response and HCV genotype, we expect an improvement of the histological features according to the probable end-of-treatment sustained virological response, because HCV infection itself could have acted as a trigger for AIH, as known. Even though IFN could exacerbate AIH, we suggest that it could have a strong indication for HCV/AIH, above all when a favourable HCV genotype and prevalent viral damage are present. Moreover we are lacking in a specific Scoring System that takes into account HCV infection as a possible trigger of autoimmune hepatitis rather than to affect negatively, since in many cases of misdiagnosed HCV/AIH, hepatologists deny antiviral therapy. References Azhar A et al. A new approach for treatment of hepatitis C in hepatitis C-autoimmune hepatitis overlap syndrome. Gastroenterol Hepatol. 2010;6:233–236

A challenging case of abdominal pain associated to Helicobacter pylori infection L. Delmonte1, C. Lunardi1, L. Frulloni1, C. Bason1, A. Rossi1, F. Busti1, G. Trecco1, A. Puccetti2, O. Olivieri1, S. Friso1 1 Department of Medicine, University of Verona School of Medicine, Policlinico ‘‘G.B. Rossi’’ Verona, Italy; 2Clinical and Experimental Immunology Unit, ‘‘G. Gaslini’’ Institute, Genoa, Italy

A 40 years-old-man was referred to the Verona University Hospital due to severe, persistent abdominal pain, nausea and vomiting. Hypocolic feces and hyperchromic urine were also reported. The patient reported the beginning of the symptoms the night before admission, following an abundant dinner and alcohol intake. On physical examination, abdominal pain was present and localized at the right hypochondrium and iliac fossa. Full blood count was unremarkable and the other biochemical exams showed high levels of bilirubin, liver transaminases and cGT (total bilirubin 82.44, indirect 78.31 lmol/L; ALT 120, AST 515, cGT 482 U/L). A moderate seric lipase and amylase increase was also observed (230 and 90 U/L, respectively). Abdominal ultrasonography (US) was negative. In the past personal medical history, he reported a similar abdomen-aching episode one month earlier. In that occasion, pain resolved spontaneously in few hours. The patient did not report further significant health problems, except for a recent diagnosis of hand-localized vitiligo. His family history was positive for gastrointestinal-tract cancer but the patient could not recall more details. At first, both clinical presentation and biochemistry data supported the hypothesis of an acute pancreatitis. However, also gallstones or biliary sludge could not be excluded. The patient was then put on fasting and abundantly hydrated intravenously but without appreciable clinical benefit while cholestasis indexes and pancreatic enzymes concentrations persisted high. Among additional blood tests, emerged an increased value of tumor marker CA 19-9 (63.45 U/mL). Despite an atypical clinical presentation, pancreatic cancer was indeed enclosed in the differential diagnosis flowchart and a magnetic resonance cholangiopancreatography (RMC) was performed. RMC showed a diffusely hypovascularized pancreatic parenchyma except for the uncinate process: after contrast medium administration, a peripheral enhancement of the gland, mostly at pancreatic head, was evident. Such imaging was

S279 consistent with an inflammatory pancreatic process. A second US, with contrast medium, was performed to exclude the presence of pancreatic masses. An extensive panel of autoimmunity tests was also completed: a mild ANA positivity (1:160) was detected. ENA were negative. A subclinical hyperthyroidism with anti-thyroglobulin and anti-thyroid-peroxidase antibodies positivity was detected. IgG subclasses measurement showed a remarkable IgG-4 fraction elevation, as previously observed in some cases of autoimmune pancreatitis. Interestingly enough, both serum Helicobacter pylori (Hp) antibodies and Hp stool antigen were positive. Hp presence was also confirmed at gastric mucosa histology on a biopsy performed during a gastroscopy, performed to exclude an upper intestinal tract-pertinence abdominal pain. Furthermore, a serum specimen was tested for the AIP(1-7) peptide, recently discovered for having significant homology with an amino acid sequence of plasminogen-binding protein of Hp and with ubiquitin-protein ligase E3 component n-recognin 2, an enzyme highly expressed in acinar cells of the pancreas. Therefore, after confirmation of the autoimmune origin of the pancreatic disease, 1 mg/kg/day prednisone therapy was started with immediate clinical benefit and rapid reduction of liver cholestasis pancreatic enzymes indices, till their complete normalization. Patient underwent also Hp-eradication therapy. After one month from beginning of treatment, also RMC showed complete remission of the signs of pancreatic inflammation. At six months from diagnosis, the patient is in good health and prednisone could be progressively tapered to 5 mg/day. In the present case, clinical presentation together with the finding of an impaired pancreatic gland vascularization at RMC, IgG4 fraction increase and signs of Hp infection, allowed the diagnosis of autoimmune pancreatitis without need of histological confirmation. Intriguing was indeed the finding of positivity for AIP(1-7) peptide which can be considered an extremely valuable marker to differentiate autoimmune pancreatitis from pancreatic cancer even in the presence of high concentrations of pancreatic cancer-specific marker, CA 19-9.

Role of the mucosal endocannabinoid system in coeliac disease A. Di Sabatino1, N. Battista2, P. Giuffrida1, L. Rovedatti1, M. Di Tommaso2, P. Biancheri1, C. Rapino2, F. Vidali1, A. Quadrelli1, A. Pasini1, M. Maccarrone2, G.R. Corazza1 1

First Department of Medicine, Fondazione IRCCS Policlinico S. Matteo, Centro per lo Studio e la Cura della Malattia Celiaca, University of Pavia, Pavia; 2Department of Biomedical Sciences, University of Teramo, Teramo, Italy Background & Aims: The endocannabinoid system has been extensively investigated in experimental colitis and inflammatory bowel disease, but not in coeliac disease where only a single study showed increased levels of the major endocannabinoid anandamide in the atrophic mucosa. On this basis, we aimed to investigate anandamide metabolism and cannabinoid receptor (CB) expression in the coeliac mucosa. Patients & Methods: We investigated the enzymes responsible for anandamide synthesis (N-acylphosphatidylethanolamine phospholipase D, NAPE-PLD) and degradation (fatty acid amide hydrolase, FAAH) in terms of transcript levels (through quantitative real time reverse transcriptase-polymerase chain reaction), protein levels (through immunoblotting) and activity levels (through radioassays) in the duodenal mucosa of 10 untreated coeliac patients, 10 coeliac patients on a gluten-free diet for at least 12 months, and 10 control subjects. The above mentioned enzymes were also quantified in treated coeliac biopsies cultured ex vivo with peptic-tryptic digest of gliadin. Moreover, the expression of CB1 and CB2 was evaluated by

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immunofluorescence through confocal microscopy in cryostat sections, and by western blotting on mucosal homogenates. Results: Our in vivo experiments showed that mucosal NAPE-PLD expression and activity are higher in untreated coeliacs than treated coeliac patients and controls, with no significant difference between the latter two groups. In keeping with the in vivo data, the ex vivo activity of NAPE-PLD was significantly enhanced by incubation of peptic-tryptic digest of gliadin with treated coeliac biopsies. On the contrary, in vivo mucosal FAAH expression and activity did not change in the three groups of patients and, accordingly, mucosal FAAH activity was not influenced by treatment with peptic-tryptic digest of gliadin. Both immunofluorescence and immunoblotting confirmed that CB1 and CB2 were expressed in the duodenal mucosa, without no significant difference between the three groups, mostly in lamina propria mononuclear cells. Of note, a considerable number of CB1-positive pericryptic myofibroblasts were evident in both untreated and treated coeliac mucosa. Conclusions: Our findings suggest an involvement of the endocannabinoid system in coeliac disease and provide a possible pathophysiological explanation for the increased anandamide concentration previously shown in active coeliac mucosa. Further studies are needed to ascertain whether CB might represent a possible target in the identification of alternative therapeutic strategies to gluten-free diet in coeliac disease.

dysphagia (PRR 2.01; 95% CI 1.46-2.75) and epigastric pain (PRR 1.28; 95% CI 1.05-1.56) than the general population, but only a higher prevalence of dysphagia (PRR 1.52; 95% CI 1.07-2.18) in comparison to choristers. When considering the occurrence of reflux symptoms in a week, soloists reported a statistically significant higher prevalence of heartburn (PRR 4.64; 95% CI 2.51-8.59), regurgitation (PRR 2.99; 95% CI 1.28-7.00), dysphagia (PRR 3.82; 95% CI 2.087.02) and epigastric pain (PRR 1.94; 95% CI 1.10-3.43) than the general population, but only a higher prevalence of heartburn (PRR 2.61; 95% CI 1.45-4.69), dysphagia (PRR 2.58; 95% CI 1.31-5.10) and epigastric pain (PRR 1.92; 95% CI 1.01-3.67) in comparison to choristers. Moreover, soloists had a higher prevalence of GERD in comparison to both the general population (PRR 5.83; 95% CI 2.62-12.95) and choristers (PRR 2.68; 95% CI 1.25-5.74). When considering the vocal register, the lowest voices (baritone, bass and mezzo-soprano) showed a significantly higher prevalence of reflux symptoms in comparison to the highest voices (soprano and tenor). Conclusions: Professional opera soloists have a higher prevalence of gastroesophageal reflux symptoms in comparison to the general population and, although to a lesser extent, to opera choristers. As the exposure of vocal cords to acid reflux may affect the quality of the vocal performance, further studies are needed to clarify whether gastroesophageal reflux in professional opera soloists may be considered as a work-related disease.

Increased prevalence of reflux symptoms in professional opera soloists

Evidence for an association of splenic hypofunction with gastrointestinal eosinophilic disorders

A. Di Sabatino1, G. Cammarota2, F. Vidali1, R. Cianci2, G. Masala3, L. Brunetti1, A. Gasbarrini2, G. Gasbarrini2, G.R. Corazza1

A. Di Sabatino, L. Rovedatti, M. Guerci, A. Quadrelli, P. Biancheri, P. Giuffrida, L. Brunetti, G.R. Corazza

1 First Department of Medicine, Fondazione IRCCS Policlinico S. Matteo, Pavia; 2Institute of Internal Medicine, Catholic University of Medicine and Surgery, Rome; 3Molecular and Nutritional Epidemiology Unit, Scientific Institute of Tuscany, Florence, Italy

First Department of Medicine, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy

Background & Aims: Gastroesophageal reflux disease (GERD) is a chronic disease that results from the abnormal exposure of the oesophageal mucosa to refluxed gastric contents, and is defined as heartburn and/or regurgitation which occur two or more days a week. Among the pathophysiological mechanisms underlying GERD, an increase of the intra-abdominal pressure that overcomes the resistance of the antireflux barrier has been hypothesized. Professional opera singers perform singing tasks that require a consistent use of the diaphragm, which causes abrupt and prolonged increase in intraabdominal pressure, deep inspiration and straining. On the basis of a previous study showing a higher prevalence of gastroesophageal reflux symptoms in professional opera choristers in comparison to the general population, we here examined a series of 116 professional opera soloists, which are supposed to be burdened by higher vocal demands during performances in comparison to professional opera choristers. Patients & Methods: A total of 116 professional opera soloists, 351 professional opera choristers and 578 control subjects, having a similar distribution in age and sex, were enrolled into the study. The prevalence of reflux symptoms in a week and in the year preceding the survey, together with individual characteristics and lifestyle habits, were investigated through a structured questionnaire. Prevalence rate ratios (PRR) adjusted for age, gender, body mass index, alcohol consumption and other confounding factors, were computed. Results: When considering the occurrence of reflux symptoms in the last year, soloists reported a significant higher prevalence of heartburn (PRR 2.17; 95% confidence intervals [CI] 1.70-2.79), regurgitation (PRR 2.11; 95% CI 1.57-2.85), hoarse voice (PRR 2.67; 95% CI 2.02-3.54),

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Background & Aims: Splenic hypofunction is an acquired condition, accompanied or not by a reduction in spleen size, which may predispose to infections by encapsulated bacteria, autoimmunity and thromboembolic manifestations. Immune-mediated intestinal diseases are the most frequently reported conditions associated with splenic hypofunction, including coeliac disease and inflammatory bowel diseases. However, no data are available in the literature regarding the association of functional hyposplenism and eosinophilic gastrointestinal disorders (EGID). EGID are rare primarily polygenic immune-mediated diseases which affect the gastrointestinal tract with eosinophil-rich inflammation in the absence of known causes for eosinophilia (i.e., drug reactions, parasitic infections and malignancy), and whose pathogenic mechanisms fall between pure IgE-mediated and delayed Th2-type responses. On this basis, we measured splenic function in a series of patients affected by EGID. Patients & Methods: A peripheral blood sample was collected from 5 patients with a known diagnosis of EGID (mean age 43.4 years; range 25-57). Twenty untreated coeliac patients (mean age 38.5 years; range 15-75), 20 splenectomized patients (mean age 58.4 years; range 23-66), and 20 healthy volunteers (mean age 51.5 years; range 29-73) were enrolled as controls for the assessment of splenic function. The latter was performed by counting pitted erythrocytes, i.e., erythrocytes with membrane abnormalities visible under interference phase microscopy as so-called pits. Briefly, 1 drop of fresh venous blood was mixed with 1.5 mL 3% buffered-glutaraldehyde solution, pH 7.4. One thousand erythrocytes were examined in a wet preparation (magnification 91000) with a direct-interference contrast microscope equipped with Nomarsky optics by an observer unaware of the sample origin. The percentage of pitted erythrocytes was calculated and taken as a measure of splenic function (upper limit of normal = 4%). Data were

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 analyzed in the GraphPad Prism statistical PC program using the non parametric Mann-Whitney U-test. A level of p \ 0.05 was considered statistically significant. Results: Four out of the 5 EGID patients (80%) had pitted erythrocyte values higher than 4% and thus were diagnosed as hyposplenic. Seven out of the 20 untreated coeliac patients (33.3%), none of the 20 healthy volunteers, and all the 20 splenectomized patients showed an impaired splenic function. The median percentage of pitted erythrocytes in EGID patients (6.2%, range 4.0-16.6) was significantly (p \ 0.001) higher than that of healthy volunteers (1.8%, range 0.53.6), but did not significantly (p = 0.057) differ from that of untreated coeliacs (2.8%, range 0.6-32.0). As expected, the median percentage of pitted erythrocytes in splenectomized patients (17.2%, range 9.432.4) was significantly higher in comparison to EGID patients (p \ 0.001), untreated coeliacs (p \ 0.0001) and healthy volunteers (p \ 0.0001). Only one out of the 5 EGID patients had a small sized spleen (maximum diameter = 7 cm) visualized at abdominal ultrasound, and 3 of them had a clinical history of atopy. Platelet counts were normal in all the EGID patients, while one of them showed positivity for anti- thyroperoxidase and anti-smooth muscle antibodies with normal thyroid and liver function tests. Conclusions: The present study reports for the first time the association between splenic hypofunction and EGID. Further studies on larger series of patients are required to assess the real prevalence of splenic hypofunction in EGID, and to clarify the pathophysiological mechanisms underlying this association.

Colonic CH4 production, breath CH4 excretion and IBS symptom M. Di Stefano, C. Mengoli, F. Racca, S. Durante, E. Miceli, M. Bergonzi, G.R. Corazza Clinica Medica I, Fondazione IRCCS Policlinico S.Matteo, Universita` di Pavia, Italy Background and Aims: It was previously suggested that the presence of breath methane (CH4) excretion makes it possible to select Irritable Bowel Syndrome (IBS) subtypes (DDS 2003; AJG 2007), but these data were not subsequently confirmed in a large series of patients (UEGW 2007). To better elucidate this issue, we studied the relationship between intestinal production and respiratory excretion of CH4 producers. Patients and Methods: A group of 56 patients was enrolled. Twentyone were affected by IBS (Rome III criteria) (12 IBS-C, 9 IBS-D), 17 by functional bloating, 7 by organic diseases. A group of 10 age and sex-matched healthy subjects formed a control group. All patients underwent severity of abdominal symptom evaluation by Visual Analogue Scale. All the subjects were given lactulose 10 g per os and underwent breath H2 and CH4 test to evaluate breath excretion and, simultaneously, the evaluation of intestinal H2 and CH4 production on gas samples collected through a catheter placed at the recto-sigmoid junction. Breath and recto-sigmoid gas samples were collected every 15 min for 7 h. Results: Thirty-one subjects proved to be CH4 non producers, non excretors. Among the 25 CH4 producers at intestinal level, 10 subjects (40%) proved to be CH4 breath excretors, while in 15 patients (60%) CH4 was not detected in breath samples. Among CH4 producers, functional bloating patients were more frequent, while IBS-C patients were less represented. Methane production was not associated with a specific symptom pattern. Breath CH4 excretion was not correlated to intestinal CH4 production (R = 0.07). Conclusions: Many CH4 producers do not excrete this gas with breath. Consequently, all the reported associations between breath

S281 CH4 excretion and clinical or pathophysiological aspects should undergo in-depth revision.

Ectopic area of gastric mucosa in esophagus and 24 h pH-impedance monitoring M. Di Stefano, C. Mengoli, M. Bergonzi, F. Racca, S. Durante, E. Miceli, E. Pagani, G.R. Corazza Clinica Medica I, Universita` degli Studi di Pavia, IRCCS Policlinico S. Matteo, Pavia, Italy Background and Aims: Heterotopic areas of gastric mucosa (inlet patches) are a frequent endoscopic finding in upper endoscopy. Patients are generally asymptomatic, but both esophageal and extraesophageal symptoms may be present and frequently overlap when GERD is evident. We hypothesized that different positioning of pH electrodes during impedance monitoring may help in the detection of acid production prom the lesions. Patient and Methods: A 40-year-old male attended our outpatient Clinic due to both reflux-related and globus. He had already undergone gastroscopy which showed erythematosus gastropathy and two areas resembling gastric mucosa at the proximal esophagus. A first standard 24 h pH-impedance monitoring (double pH sensor, Sandhill Scientific) revealed severe acid exposure of the distal third of the esophagus (17.3% of total recording time, 21.8% supine, 12.8% upright) with 29 acid and 41 weakly acid reflux episodes. Visual analysis of the recording showed mismatch between gastric and esophageal pH: in 15 occasions, pH value of distal esophagus was lower than gastric pH and impedance waves were caudally transmitted, suggesting a proximal site of production of this acid material in esophageal, rather than gastric refluxate. To ascertain the origin of acid, we performed a second pH impedance monitoring by using a modified protocol: pH sensors were placed respectively 20 and 5 cm above the LES, and so impedance sensors at a more proximal level, after about two weeks of high dose PPI therapy, due to inadequate response. Results: The patient partially improved during PPI therapy. The second examination showed 35 pH modifications. 8 acidic and 7 non-acidic reflux episodes with proximal extent were observed, not associated with symptoms. The remaining twenty episodes of esophageal pH modification were characterized by an initial fall at proximal level, followed by the fall at distal level, not associated with deglutition of alimentary bolus. Impedance waves revealed acidic liquid descending along the esophagus, with saliva deglutition. The patient reported epigastric pain or heartburn in the majority of these events (SAP respectively 98% and 99%). Conclusion: 24 pH-impedance acid monitoring could be a useful tool in detecting acid secretion originating from the inlet patch, clarifying its role in non-responder GERD patients.

False positivity of hydrogen breath test in patients with severe constipation M. Di Stefano, C. Mengoli, M. Bergonzi, F. Racca, S. Durante, E. Miceli, E. Pagani, G.R. Corazza Clinica Medica I, Universita` degli Studi di Pavia, IRCCS Policlinico S. Matteo, Pavia, Italy Background and Aim: The diagnostic accuracy of the hydrogen breath test might be reduced by the release of preformed hydrogen, persisting in the colon, trapped in hard stools. Since the ingestion of

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S282 the test solution might induce the mixing of colonic content and a false positive result, we studied severely constipated patients in an attempt to clarify whether this mechanism affects test results. Methods: In a tertiary care setting, we studied 20 consecutive functional constipated patients (Bristol scale 1 and 2 in 10; Bristol scale [2 in 10), 10 consecutive patients with functional diarrhea and 10 healthy volunteers. On different days, the subjects underwent (a) a hydrogen breath test after lactulose, to exclude differences in fermenting capacity among the groups; (b) breath hydrogen excretion monitoring after colyte, a non absorbable, non fermentable solution, to exclude the role of the delivery to the colon of pre-existing fermentable substrates or of the release of preformed H2 entrapped in the feces; (c) H2 measurement during a 7-hour fasting period, to exclude the role of spontaneous variations of breath gas excretion. Results: All the subjects excreted similar amounts of hydrogen both after lactulose and during prolonged fasting. On the contrary, after colyte, 7 out of 10 patients showed an increase of breath H2 excretion over 12 ppm compared to fasting values only in the group of severely constipated patients (Bristol scale 1 and 2); in 5 of them this increase was over 15 ppm. None of the patients in the other groups showed a similar excretion pattern. Accordingly, both peak and cumulative breath H2 excretion were significantly higher than in the other three groups. Conclusion: Severely constipated patients may harbour preformed gas in hard stools which can be released when mixing of the intestinal content is induced. This mechanism may interfere with breath test results: the detected levels of H2 excretion may induce a 50% false positivity of glucose breath test and a 70% false positivity of the lactose breath test in these patients.

Dietary iron overload induces visceral adipose tissue insulin resistance associated with hyper-resistinemia, and synergizes with obesity in inducing systemic insulin resistance P. Dongiovanni, M. Ruscica, L. Benedan, V. Borroni, S. Recalcati, L. Steffani, G. Cairo, P. Magni, F. Caprioli, S. Gatti, S. Fargion, L. Valenti Department of Internal Medicine, Universita` degli Studi di Milano, Ospedale Maggiore ‘‘Ca’ Granda’’ Policlinico IRCCS, Milan, Italy Introduction: Excess body iron is frequently observed in patients with metabolic syndrome (MetS), and associated with insulin resistance (IR) and organ damage. However, whether iron overload has a causal role in the pathophysiology of MetS is not well understood. Aim was to assess the effects of dietary modulation of iron status on IR and to investigate the underlying mechanisms in mouse models. Methods: Wild-type or ob/ob 4 week-old male C57BL/6 mice were fed for 16 weeks a standard iron concentration diet (8 mg/kg, n = 15) or an iron enriched diet (30 g/kg:IED, n = 15), with/without highfructose diet (HFD). Results: IED was associated with increased serum/hepatic iron (comparable to that observed in patients with MetS). Despite IED reduced weight gain, due to reduced visceral adipose tissue mass (VAT; perigonadal fat pad: -60%, p = 0.02), it induced a progressive increase in glucose due to IR, confirmed by i.p. insulin tolerance test. In ob/ob mice IED led to overt diabetes and in HFD fed mice increased IR by about 100%, associated with decreased VAT despite no changes in total body mass, thus suggesting VAT-IR. IED increased VAT-IR, as shown by decreased fasting pAKT/AKT ratio (-80%, p = 0.03), and VAT iron accumulation with oxidative stress and UPR activation. In addition, IED induced increased VAT resistin mRNA levels (p = 0.005), which resulted in hyper-resistinemia

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 (p = 0.01) and increased VAT expression of SOCS3 (p \ 0.05), a resistin target implicated in the pathogenesis of IR. Discussion and Conclusions: IED induces VAT-IR in C57/BL6 mice and synergizes with obesity in the pathogenesis of metabolic complications.

Over time changes of serum alpha-fetoprotein as surveillance test for hepatocellular carcinoma development in cirrhotic patients G. Fatti1, M. Frigerio1, F. Conti1, E. Loggi1, D. Buccione1, A. Di Micoli1, V. Santi1, P. Del Poggio2, E. Giannini3, F. Farinati4, P. Andreone1, M. Bernardi1, F. Trevisani1 Dip. di Medicina Clinica, Universita` di Bologna; 2Div. di Medicina, Osp. Treviglio-Caravaggio, Treviglio; 3Dip. di Medicina Interna, U.O. Gastroenterologia, Universita` di Genova; 4Dip. di Sc. Chirurgiche e Gastroenterologiche, Universita` di Padova, Padova, Italy 1

Background: International guidelines for HCC management recommend a regular liver ultrasound (US) surveillance of at risk population for HCC development, considering that the early detection of the tumour allows applying curative or effective therapies, greatly improving the prognosis. Nowadays, the use of alpha-fetoprotein (AFP) in surveillance programs is no longer recommended due to its poor accuracy. Nonetheless, this seromarker remains superior to any other seromarkers tested for the early HCC detection. The evaluation of the overtime behaviour of AFP could improve its accuracy, erasing any ‘determination bias’. Aim: to evaluate the performance of an over time elevation of serum AFP as surveillance test for HCC compared with a single AFP determination in patients with liver cirrhosis. Materials and Methods: from a cohort of 1068 cirrhotic patients, seen consecutively from January 1st 2000 to February 21st 2009 in 4 Italian referral centres for HCC, we retrospectively selected those who developed HCC (cases) during a regular semiannual surveillance program based on liver US and AFP measurement. Inclusion criteria were the availability of: Child-Pugh class, cancer stage and serum AFP one year and 6 month before and at the time of HCC diagnosis (time 0). We enrolled 80 cases. Each case was matched with two cirrhotic patients (160 contemporary controls) followed in the same period who remained cancer-free. To align AFP measurements we considered as time 0 for controls the date of the AFP measurement closest to the date of HCC diagnosis of the corresponding case. Controls must remain cancer-free even in the year following time 0. Matching criteria at time 0 were: age (±5 years), gender, aetiology of cirrhosis, Child-Pugh class, ongoing antiviral therapy (patients who stated or stopped the treatment during the 18 months preceding time 0 were excluded). The Receiver Operating Characteristic (ROC) curve and the corresponding area under the curve (AUC) were calculated to provide the accuracy of serum AFP in distinguishing HCC patients from cirrhotic patients. The overtime changes (D) of AFP were calculated as differences between the time 0 value and -6 month value (AFP-D6) or -12 month value before (AFP-D12). Sensitivity (Se), Specificity (Sp), Positive (PPV) and Negative (NPV) Predictive Values (considering for PVs both the actual prevalence (33%) and a 3% prevalence of HCC, the latter matching that expected in a clinical setting) were calculated. Results: No significant differences between cases and controls were found for serum ALT, AST, bilirubin and creatinine. Control patients had significantly higher albumin and cases higher INR. At time 0, AFP was significantly higher in case than in control patients (median 17.5 ng/ml [range: 60 to 1238 ng/ml] vs. 5.0 ng/ ml [range: 1.0 to 75.0 ng/ml], P \ 0.001). The median AFP-D6

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Contrast enhanced ultrasound in the differential diagnosis of exocrine vs. endocrine pancreatic tumors C. Felicani, E. Mazzotta, C. Serra, M.L. Cipollini, C. Caputo, A.M. Morselli Labate, L. Piscitelli, D. Fabbri, A. Imbrogno, M. Cevenini, E. Guidetti, R. De Giorgio, R. Pezzilli, G. Barbara, V. Stanghellini, P. Tomassetti, R. Corinaldesi Department of Clinical Medicine University of Bologna, D.A.I. Gastrointestinal and Internal Medicine Diseases St.Orsola-Malpighi Hospital, Bologna, Italy Contrast-enhanced ultrasonography (CEUS) is an approach providing real-time dynamic data on macro- and micro-circulation of focal lesions in several organs, including pancreas. CEUS is useful in the differential diagnosis of solid vs. cystic pancreatic tumors as previously demonstrated. Aim: The aim of this study was to evaluate the ability of CEUS to characterize the vascularization pattern of solid pancreatic tumors and, specifically, to differentiate exocrine vs. endocrine tumors. Methods: 86 patients (52 males and 34 females; mean age, 63 ± 11 years, range 45-85 years) with a solitary undetermined pancreatic mass were prospectively examined with B-Mode ultrasound (US) and CEUS, prior to surgical resection or percutaneous biopsy. Pulse inversion technique with intravenous injection of 2.4 ml of SonoVue as contrast agent, were used for the CEUS. Results: Exocrine pancreatic tumors occurred more frequently in males, were predominantly hypoechoic at US examination and most often localized to the pancreatic head. Conventional US resulted inadequate to identify exocrine tumors. In contrast, CEUS showed a good diagnostic accuracy (93%) in differentiating endocrine from exocrine tumors. Sensitivity and specificity were 100% and 86.4%, respectively, with a 95.5% positive predictive value (PPV), and a 100% negative predictive value (NPV). CEUS improved US diagnostic accuracy by increasing sensitivity from 89.1% to 100%, specificity from 72.7% to 86.4% (13,7%), PPV from 90.5% to 95.5% (5.0%) and NPV from 69.6% to 100 % (30,4%). The CEUS-related hypovascular pattern allowed the identification of exocrine pancreatic tumor with a sensitivity of 100% and a 95% of PPV, whereas the hypervascular pattern allowed the detection of endocrine pancreatic tumors and other conditions (including 2 cases of pancreatic metastases) with a specificity of 86.4% and a 100 % of NPV.

Conclusion: This study showed that CEUS has a good diagnostic accuracy in differentiating endocrine from exocrine pancreatic tumors, a fundamental step to address appropriate diagnosis and therapeutic approach for pancreatic malignancies.

A successful first line sequential therapy for naı¨ve H. pylori positive patients: a 10 years experience G. Fiorini1, L. Gatta 2, C. Ricci3, V. Castelli1, I. Saracino1, A. Zullo4, D. Vaira1 Dipartimento di Medicina Clinica, Universita` di Bologna, Bologna, Italy Background: resistance has decreased eradication rates for Helicobacter pylori infection worldwide. Aim: 1) to re-evaluate the performance of sequential therapy (ST) after nearly 10 years from the first study performed in our centre; 2) to assess the antimicrobial resistances and their impact on the eradication rate of sequential treatment. Methods: 197 (M/F: 77/120; median age 51 years, IQR: 39-63) naı¨ve H. pylori infected patients who underwent an EGDS were treated with a 10-day sequential regimen (40 mg of Esomeprazole, 1 g of amoxicillin, each administered twice daily for the first 5 days, followed by 40 mg of Esomeprazole, 500 mg of clarithromycin, and 500 mg of tinidazole, each administered twice daily for the remaining 5 days). 13 C-UBT, histological evaluation, and bacterial culture to assess antibiotic resistance (E-test) to clarithromycin (C), metronidazole (M), and Levofloxacin (L) were performed at baseline. Eradication was assessed 4 weeks after the end of the treatment with 13C-UBT. Results: The eradication rate according to the ITT analysis was 96.4% (95%CI: 93 to 99). Strains resistant to C were 21.1% (95% CI: 15.8 to 27.6), to metronidazole 39.4% (95% CI: 32.6 to 46.7), and to Levofloxacin 26.8% (95% CI: 20.9 to 33.7). Strains resistant to both C and M were 15.1% (95%CI: 10.6 to 21.1). ST eradicated 90% (95% CI: 75.9 to 95.8) of C-R strains, 95.8% (95% CI: 88.3 to 98.6) of M-R strains, and 88.9% (95% CI: 71.9 to 96.1) of C and M resistant strains. The pooled eradication rate of all trails performed in our centre using a random model was 93.6% (95%CI: 88.7 to 97.7), and the eradication rates in strains resistant to C, M and C + M remained constant despite an increase in prevalence from 2003 of strains resistant to C (p \ 0.001), M (p \ 0.001), and C+M (p \ 0.01). Conclusions: ST continues to be a high effectively treatment in our centre to eradicate H. pylori infection despite a significant increase in primary resistant to antibiotics.

Results: ERs of ST in RSs during the years Cla-R

Metro-R

Cla-R+Metro-R

120 100

Prevalence (%)

value was 2 ng/ml (range: 20 to 1110 ng/ml) in cases and 0 ng/ml (range: -94 to 36 ng/ml) in controls (P \ 0.001). The median AFP-D12 value was 4.6 ng/ml (range: -22.3 to 1228 ng/ml) in cases and 0 ng/ ml (range -308 to 34 ng/ml) in controls (P \ 0.001). The AUC of the ROC curve of AFP at time 0 (0.760 ± 0.036) was higher that the AFP-D6 AUC (0.714 ± 0.040) and the AUC of AFP-D12 (0.724 ± 0.040). The best cut-off value of AFP at time 0 was 10 ng/ ml, with Se of 66%, Sp of 81%, PPV of 63% and NPV of 83%. At the simulated HCC prevalence of 3%, PPV and NPV were 10% and 99%, respectively. Conclusion: The AFP cut-off value (10 ng/mL) that should raise the suspect of HCC occurrence in cirrhotic patients maintained under surveillance is much lower than that used in clinical practice (20 ng/ml). However, using even this new value the accuracy of AFP remains inadequate, since its Se and PPV are unacceptable, missing an early HCC diagnosis in most cases. Moreover, the monitoring of the changes of AFP during both the 6 and 12 months preceding tumour diagnosis does not ameliorate the performance of this seromarker. Our results do not suggest reconsidering the role of AFP as surveillance test for an early diagnosis of HCC in cirrhotic patients.

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97

94

96,6 90,6

89

90,9

80 78 70

60 40 20 0

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Ann Intern Med 2007

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S284 An insidious case of diagnostic - operative colonoscopy P. Ghiringhelli, L. Furlan, R. Cattaneo Azienda Ospedaliera di Busto Arsizio, Dipartimento Medico P.O. Tradate, S.C. Medicina, Italy The differential diagnosis of abdominal pain in Internal Medicine is complex. The clinical case becomes even more complex if symptoms occured in a chronic psychotic patient. History: Women of 62 years with colon diverticulosis and known for a decade, and in treatment, for psychotic depression. After 15 days of onset of abdominal pain, prevalent in left iliac fossa, appeared an unusual constipation. Physical examination showed mild tenderness to deep palpation localized in the left iliac fossa. Colonoscopy: at about 25 cm. from the anal margin was discovered the presence of a foreign hard body, the length of it was about 5 cm. and a diameter of about 4 mm. with an extension hook. Both ends were stuck in the wall. In the point of contact was present an inflammatory granulation tissue around the foreign body as a subacute inflammatory reaction. The foreign body proved to be a bone of rabbit. The symptoms disappeared immediately after the removal of bone. Conclusion: The particularity of this case is related to the progression of the foreign body through the alimentary canal, with the overcoming of natural strictures: esophageal, pyloric, small intestine and ileo-cecal valve, and then fixed dangerously in the sigmoid wall.

Health-related quality of life in patients with functional gastrointestinal disorders G. Gigante1, A. Tortora1, V. Ojetti1, F. Bertucci1, P.M. Ferraro2, M. Campanale1, V. Cesario1, G. Caracciolo1, F. Barbaro1, F. Purchiaroni1, F.R. Ponziani1, G.B. Gasbarrini3, G. Bombardieri1, A. Gasbarrini1 1

Internal Medicine And Gastroenterology, Gemelli Hospital, Rome; Nephrology-Renal Program, Gemelli Hospital, Rome; 3Fondazione Ricerca In Medicina, Bologna, Italy 2

Introduction: A low health-related quality of life (HRQL) was reported in subjects with functional gastrointestinal disorders (FGDs). Lactose intolerance, other sugars intolerances, small intestinal bacterial overgrowth, alterations of gastrointestinal transit time, dyspepsia are very common in clinical practice, and could be investigated with breath test (BT) analysis. The Short Form Health Status Survey (SF36) demonstrated internal consistency, construct validity and concurrent validity when applied to patients (pts) with significant bowel dysfunction. Aims & Methods: To assess, by SF36, the impact of FGDs on HRQL of pts that perform BT. We consecutively enrolled, from the Gastroenterology Unit of Policlinico Gemelli in Rome, 96 pts (61F, 35M; age mean 40 ± 15 yrs) with FGDs who underwent H2BT and/or C13 Urea BT. HRQL was analyzed on SF36 scores and component summary scores. For each item, the mean difference and 95% confidence interval (CI) with corresponding two-tailed P-values between the pts and the general population were calculated by means of a z-test. Results: All items analyzed by SF36 were lower compared to the normal values for the general Italian population. Mean Mental Health Index (MHI) and Physical Health Index (PHI), the two main scores of SF 36, were both under the normal values for the general population: MHI 39.1 ± 11.8 (nv 50, mean difference -10.9, 95% CI -15.0, -6.7; P \ 0.001); PHI 45.8 ± 9.0 (nv 50, mean difference -4.2, 95% CI 7.4, -1.1; P = 0.010).

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Conclusion: Pts submitted to BT showed a lower SF36 scores compared to general population. Therefore FGDs have a significant impact on HRQL of pts in particular this kind of pts showed a significant reduction of MHI. SF36 could provide a useful adjunct to current methods of evaluating treatment outcomes for FGDs, and potentially other disorders. Keywords: Functional Gastrointestinal Disorders (FGDs), Health Related Quality of Life (HRQL)

A very rare cause of obscure-overt gastrointestinal bleeding C.M. Girelli, B. Nardo, R. Casieri, E. Gjoni, G. Bernasconi UOC Medicina a Indirizzo Gastroenterologico e UOC Chirurgia Generale. Ospedale di Circolo di Busto Arsizio, Italy A 62 years old man was referred to our Unit for intermittent obscureovert gastrointestinal bleeding, started from two months, requiring up to three units of packed red blood cells (RBC) weekly. His clinical history was noteworthy for urgent right hemicolectomy due to rightsided colonic diverticulitis, occurred 8 years before admission. Previous upper and lower endoscopy, and angiography were negative. On admission, he presented melaena; he was hemodynamically stable and his haemoglobin level was 6.8 g/dL. After RBC replacement, he underwent capsule endoscopy (CE) which disclosed fresh blood in the upper quartile of the small bowel (24% of the time elapsed from the pylorus). The next day he underwent an unremarkable push enteroscopy, allowed for 60 cm beyond the ligament of Treitz. On the third day of hospitalization, a second CE unveiled a tiny round mucosal break suggestive for Dieulafoy lesion (DL), located in the mid small bowel (52% of the time elapsed from the pylorus). In consideration of 1) active bleeding, 2) distance of the lesion from mouth and anus, 3) uncertainty on the best route of insertion of device assisted enteroscopy, 4) the risk of poor enteroscope progression due to likely adhesions from previous surgery, and 5) the low surgical risk, we decided to perform an intra-operative enteroscopy (IOE). A complete IOE was done across a small enterotomy, performed next to a visible clot. A 3 mm area of denudated bleeding mucosa, located 5 cm above the enterotomy, was the only identified mucosal abnormality. A 15 cm ileal resection with side-to-side anastomosis was performed. The patient stopped to bleed, the postoperative period was uneventful, and DL was pathologically confirmed. Ileal DL is exceedingly rare and, to the best of our knowledge, this is the first reported case diagnosed by CE. When CE shows only luminal blood, the bleeding point localization is unreliable, and a second look CE may be helpful to identify the source of bleeding. Although in the era of device assisted enteroscopy the best management of ileal DL is controversial, we believe that IOE and surgical resection is still the gold standard for these tiny, deep-seated, dreadful vascular abnormalities.

One-hour post-load plasma glucose levels are associated with elevated liver enzymes A. Grembiale, F. Iorio, S. Mastroianni, T.V. Fiorentino, E. Succurro, F. Arturi, M.L. Hribal, F. Perticone, G. Sesti Department of Experimental and Clinical Medicine, University ‘‘Magna-Græcia’’ of Catanzaro, Catanzaro, Italy Background: Subjects with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) are at high risk for the future development of type 2 diabetes. However, there is evidence that 30-40% of individuals who develop type 2 diabetes have normal

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 glucose tolerance (NGT) at baseline Recently, it has been shown that a cut point of 155 mg/dl for the 1-hr post-load plasma glucose during the oral glucose tolerance test (OGTT) is able to identify subjects at relatively high risk for development of type 2 diabetes among those who have NGT or IGT. Moreover, NGT subjects with 1-h plasma glucose C155 mg/dl exhibit a worse cardio-metabolic risk profile and early signs of vascular atherosclerosis. Several prospective studies have shown that high levels of ALT and GGT are independent predictors of incident type 2 diabetes. However, it is unknown whether NGT-1 h-high are at increased risk for higher levels of liver biomarkers. Aims: The aim of this study was to assess whether Caucasian subjects with elevated 1-h post-load plasma glucose are at increased risk for having higher circulating levels of liver biomarkers associated with NAFLD. Methods: The study group consisted of 1000 nondiabetic Caucasian subjects participating to the CATAnzaro MEtabolic RIsk factors (CATAMERI) Study, a study assessing cardio-metabolic risk factors in individuals carrying, at least, one risk factor including elevated blood pressure, dyslipidemia, dysglycemia, overweight/obesity, and family history for diabetes or cardiovascular disease. After 12-h fasting, subjects underwent complete anthropometrical evaluation and a venous blood sample was drawn for laboratory determinations. On the second day, after a 12-h overnight fast, a 75 g OGTT was performed with 0, 30, 60, and 120 min sampling for plasma glucose and insulin, and subjects were classified as NGT (fasting plasma glucose [FPG] \126 mg/dl and 2 h post-load \140 mg/dl) or IGT (FPG \126 mg/dl and 2 h post-load 140 –199 mg/dl). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gammaglutamyltransferase (GGT) levels were measured in all the subjects. Results: Of the 1000 subjects examined, 752 (75,2%) had NGT, and 248 (24,8%) had IGT. We divided the subjects with NGT into two groups: 532 subjects with 1-hour post-load plasma glucose \155 mg/dl (NGT 1 h-low), and 220 individuals with 1-hour post-load plasma glucose C155 mg/dl (NGT 1 h-high). NGT-1 h-high had increased levels of ALT and GGT, but not AST, as compared with NGT 1 h-low. After adjustment for age and gender, ALT, AST and GGT levels were all significantly correlated with BMI, waist circumference, blood pressure, triglycerides, fasting and post-challenge glucose and insulin levels. In a logistic regression analysis adjusted for age, and gender, NGT-1 h-high had increased risk of having ALT in the highest quartile compared with NGT-1 h-low (OR = 1.71, 95%CI 1.16–2.52). NGT-1 h-high also exhibited increased risk to have GGT in the highest quartile (OR = 1.50, 95%CI 1.02–2.17). These associations remained significant after adjustment for BMI, blood pressure, and lipids, but not after further adjustment for an insulin sensitivity index. NGT 1 h-high subjects had increased risk of having AST in the highest quartile compared NGT 1 h-low group (OR = 1.51, 95%CI 1.04–2.22). This association was not significant after adjustment for BMI, blood pressure, and lipids. Conclusions: In our study, we documented significant cross-sectional associations of biomarkers of NAFLD, including ALT and GGT, and to a lesser extent AST, with elevated 1-h post-load plasma glucose during the OGTT in glucose tolerant subjects. These data suggest that a 1hPG C155 mg/dl cutoff may be helpful in the identification of NGT individuals at risk for liver abnormalities.

Hospital anxiety and depression scale (HADS) in a small cohort of IBD patients: results from a multidisciplinary approach L. Laterza1, F. Scaldaferri1, D. Ferrarese1, M. Pizzoferrato1, E. Gaetani1, L. Lopetuso1, S. Pecere1, V. Gerardi1, F. Forte1, A. Poscia2, G. Gasbarrini3, A. Gasbarrini1

S285 Istituto di Patologia Speciale Medica, 2Istituto di Igiene,Universita` Cattolic a del Sacro Cuore, 3Fondazione Ricerca in Medicina Onlus, Bologna, Italy

1

Introduction: Stress and IBD are extremely interdependent. Relapses can be associated to stressful events and anxiety or depression could occur especially during active disease. HADS is one of the most reliable test in assessing anxiety and depression, but its use in IBD has not been explored deeply. Aims & Methods: To investigate the prevalence of anxiety and depression assessed by HADS in a cohort of IBD patients. Patients underwent to control visit completed the HADS questionnaire, together with a visual wellbeing assessment scale (VWAS), completed by the patient (P-VWAS) and also by the gastroenterologist during the visit (G-VWAS). Patients were also checked for levels of C reactive protein (CRP), Erythrocyte sedimentation rate (ESR) and fecal calprotectin (FC). HADS was considered to be negative for scores lower than 8, indeterminate between 9 and 10 and positive for score higher than 10. The VWAS was considered normal for scores higher than 7 and abnormal for scores lower than 6. Results: Twenty seven IBD patients were enrolled (18 female, 46 y mean age). The prevalence of anxiety and depression (A-D prevalence) was 55% (58% in female and 40% in male) while 30% of patients had a borderline score. The A-D was not apparently associated to the subjective perception of wellbeing as it was 50% in patients with normal PVWAS and 55% in patients with impaired P-VWAS. Instead, from the physician perspective, A-DP was higher (71%) in patients with an impaired G-VWAS but lower (50%) in patients with a normal G-VWAS. In the subgroup of patients with low levels of FC (\100 mg/Kg) A-DP was 50% compared with 75% of patients with higher levels of FC ([100 mg/Kg). Comparing the P-VWAS to the G-VWAS, a concordance was found in 52% of cases (13 patients, 35% in women and 70% in male), with a down-estimation in a 91% of cases. In these patients the A-DP was not higher than the one found in patients with concordance of wellbeing perception scores (58% vs 66%), suggesting that other psychological mechanisms beside anxiety or depression could participate in this phenomenon. Conclusion: Despite their importance, A/D are not crucial in determining the self-perception of the disease. HADS could help in discriminating patients that would benefit from a multidisciplinary approach, particularly among patients displaying higher levels of FC or lower levels of G-VWAS. The high level of discordance among P and G-VWAS suggests that other complex psychological mechanisms could participate in wellbeing perception.

Autoimmune liver diseases in Southern Italy: a retrospective cohort study A. Licata, N. Alessi, F.S. Macaluso, A. Costantino, A. Calı`, P.L. Almasio, A. Craxı` Gastroenterologia ed Hepatologia. Di.Bi.M.I.S. Universita` di Palermo, Palermo, Italy Background and Aim: Autoimmune liver diseases (ALD) are chronic inflammatory illnesses characterized by loss of immunological tolerance against hepatocytes and/or cholangiocytes which comprise Primary Biliary Cirrhosis (PBC), Primary Sclerosing Cholangitis (PSC), Autoimmune Hepatitis (AIH) and Overlap Syndromes. We describe the socio-demographic and disease features at onset in ALD patients from Southern Italy.

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S286 Patients and Methods: All records of patients with a diagnosis of ALD seen at our tertiary referral Unit between January 2001 and 2011 were retrospectively reviewed focusing on socio-demographic, clinical, biochemical and histological features at onset. Diagnosis of AIH was based on International Autoimmune Hepatitis Group criteria, diagnosis of PBC and PSC was made following AASLD guidelines. Results: Out of approximately 7,000 patients with liver disease admitted to our Unit, 129 subjects were diagnosed as ALD (PBC = 65, AIH = 45, PSC = 7, Overlap Syndromes = 12). PBC patients were predominantly females (93.6%) with a mean age of 51.7 years (range 34-85). Most of the patients were asymptomatic at the onset (56.9%). Anti-mitochondrial antibodies (AMA) were detected in 61 patients (93.8%) and anti-nuclear antibodies (ANA) were positive in 24 patients (36.9%). Histological findings were staged according to Scheuer’s scale: 47 (72.3%) showed early stage (I-II), 18 (27.7%) advanced stage (III-IV). PBC patients were also subdivided into three groups: age \40 years (12 cases), age between 40 and 65 years (43 cases) and age [65 years (10 cases). Patients younger than 40 years had higher alanine aminotransferase (p = 0.02) and alkaline phosphatase levels (p = 0.047), while patients between 40 and 65 years had a higher frequency of ANA positivity (P = 0.004) and a more symptomatic disease at onset (p = 0.03). Majority of patients with AIH were females (88.9%) with a mean age of 54.5 years (range 17-85). ANA were positive in 35 patients (77.8%), anti-smooth muscle antibodies (SMA) in 15 patients (33.3%), anti-liver kidney microsomal antibodies-1 (anti-LKM1) in 5 patients (11.1%). At diagnosis one third of subjects were asymptomatic and cirrhosis was very rare (8.9%). Conclusions: In our PBC patients sex distribution, frequency of autoantibodies and histological stage at diagnosis were similar to other cohorts. Subgroup analysis showed a higher biochemical activity in younger patients and a more symptomatic disease in middle-age subjects. In AIH patients mean age at diagnosis was higher than expected; this could be related to a referral bias or to a delayed diagnosis, but a different genetic background of our population cannot be excluded.

Drug-induced liver injury and non-organ specific autoantibodies (NOSAs): an epiphenomenon or an autoimmune disease? A. Licata, G. Butera, F.S. Macaluso, C. Randazzo, I. Bravata`, M. Cappello, P.L. Almasio, A. Craxı` Gastroenterologia ed Hepatologia. Di.Bi.M.I.S. Universita` di Palermo, Palermo, Italy Background & Aim: Drug-induced liver injury (DILI) is increasingly being recognized as a common cause of liver disease. Non organ specific autoantibodies (NOSAs) as well as clinical, laboratory, and histological features of an autoimmune-like liver disease may be present in some patients with DILI. We aimed to assess the proportion of NOSAs among consecutive, well-characterized patients with DILI. Furthermore, we sought to compare the clinical and biochemical characteristics of patients with and without NOSAs. Methods: Between 1996 and April 2011, all records of consecutive patients diagnosed as DILI seen at our tertiary referral centre were analyzed. Data were collected from in- and outpatient visit charts. Diagnosis of DILI was made when at least three of the International Consensus Criteria (J Hepatol 1990) were present. According to clinical and laboratory data, we defined liver damage as cytolitic, cholestatic or mixed. All patients had regular follow-up visits every six months for at least one year, and were recontacted to update outcomes. Antinuclear (ANA), anti smooth muscle (SMA),

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 antimitochondrial (AMA), anti liver-kidney microsome-1 (LKM-1) antibodies were tested in all patients by indirect immunofluorescence. Patients with pre-existing chronic liver disease were excluded. Results: Out of 10,270 patients, 101 (49 males, mean age 51,8 years, range 11-87) fulfilled the diagnostic criteria of DILI. Most common involved drugs were NSAIDs (29.5%), antibiotics (25.7%), immunosuppressants (11.9%), antiplatelet (7.9%) and psychotropic (7.9%) agents. Clinical patterns of liver damage were as follows: cytolitic 41 (40.6%) cases, cholestatic 34 (33.7%), mixed 26 (25.7%). Jaundice at onset was evidenced in 40 (39.6%) subjects. Only 17 patients (17%) had been undergone to corticosteroidal therapy. According to positivity of NOSAs, patients were divided in two groups: 32 (31.7%) with NOSAs (Group A) and 69 (68.3%) without NOSAs (Group B). Amongst group A autoantibodies positivity was 23 ANA+, 6 SMA+, 3 ANA+/SMA+. By statistical analysis, comparing group A with group B, we found a higher frequency of NOSAs positivity in patients aged between 40 and 65 years (62.5% vs. 29.0%, p = 0.006). No differences were found among NSAIDs and antibiotics as cause of DILI, except for anti-platelet agents (Group A, 18.7 vs. Group B, 2.9, p = 0.0117). Group A and group B did not show any difference by age at onset, gender distribution, pattern of liver injury, liver stiffness, need for corticosteroid therapy and clinical outcome. Overall, chronicity occurs in 5 patients, 2 of group A and 3 of group B; only two died. Complete recovery occurred in 52% of patients, (40% in Group A, 57% in Group B); the remaining patients are still in follow-up. Conclusions: DILI may present with clinical and biochemical features resembling autoimmune liver diseases. NOSAs are not necessarily markers of autoimmune liver disease, even if corticosteroidal therapy sometimes is needed, as well. However, our results suggest a closer monitoring of patients with DILI and incomplete recovery.

Amoxicillin-clavulanate as a leading cause of severe drug-induced liver injury A. Licata, G. Butera, V. Calvaruso, C. Randazzo, M. Cappello, A. Almasio PL Craxı` Gastroenterologia ed Epatologia. Di.Bi.M.I.S. Universita` di Palermo, Palermo, Italy Background & Aim: Drug-induced liver injury (DILI) is increasingly being recognized as a cause of liver disease. Its clinical presentation covers a wide spectrum, from mild LFTs alterations to severe hepatocellular damage. Recognizing and diagnosing of DILI are often difficult and delayed due to the need to exclude more common competing causes of liver injury. We aimed to evaluate the rate of severe cases of DILI on total hospital admissions and to identify the drugs most commonly responsible of this clinical course. Methods: Between 1996 and April 2011, all records of consecutive patients diagnosed as DILI seen at our tertiary referral centre were analyzed. Data were collected from in- and outpatient visit charts. Diagnosis of DILI was made when at least three of the International Consensus Criteria (J Hepatol 1990) were present. According to clinical and laboratory data, we defined liver damage as cytolitic, cholestatic or mixed. All patients had regular follow-up visits every three months for at least one year, and were contacted to update outcomes. Results: Out of 10,270 patients, 133 (65 males, median age 54 yrs, range 11-88) fulfilled the diagnostic criteria of DILI. Mean age was 53 years (range 11-88), with 70% of subjects older than 40 years. Thirty-two patients (24%) had pre-existing compensated chronic liver disease (CLD). Cytolitic pattern was more commonly observed (50.4%) followed by cholestatic (30%) and mixed pattern (20%). Preexisting CLD was associated with the cytolitic pattern of injury

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 (P 0.004). The most frequent drugs were non-steroidal anti-inflammatory drugs (NSAIDs; 29%), followed by antibiotics (23%), immunosuppressant (13%), anti-platelet agents (8%), anti-diabetic drugs and statins (15%). In 26 (19.5%) of cases, two or more drugs were involved. Among antibiotics, Amoxicillin-Clavulanate was more frequently associated with hepatocellular pattern (P = 0.037) and jaundice. Liver stiffness measurement by transient elastography (Fibroscan) was carried in 50 (38%) patients. Antibiotics group showed higher liver stiffness values as compared to NSAIDs group (17.5 Kpa vs 15,7 Kpa respectively) (P = 0.004). Acute liver failure developed in 9 (6.8%) and 2 died (1.5%). Overall, complete recovery occurred in 50.2% of patients, with no difference between patients with and without CLD Conclusions: DILI is an important cause of hospitalization for acute liver disease in patients over 40 years. NSAIDs and antibiotics were the most frequent causes of DILI. Amoxicillin-Clavulanate was more frequently associated with severe liver damage as showed by highest liver stiffness values.

Tanagel reduce colitis severity in dextran sodium sulphate (DSS) model of murine acute colitis L.R. Lopetuso, F. Scaldaferri, V. Cufino, V. Petito, V. Gerardi, M. Pizzoferrato., S. Pecere, L. Laterza, E. Stigliano, V. Arena, A. Sgambato, A. Gasbarrini Istituto di Patologia Speciale Medica – UOC di Medicina Interna e Gastroenterologia, Universita` Cattolica Sacro Cuore, Roma Introduction: Tanagel, a gelatin powder containing Tannic Acids, is commonly used for diarrhea in children. Few information exist on its mechanisms of action, involving gel formation and bacterial toxin sequestration, mostly obtained by in vitro studies. No information, however, exist regarding in vivo studies and no animal model has been used to confirm its efficacy or unravel further mechanism of action. Aims & Methods: Aim of this study was to evaluate the therapeutic effect and mechanisms of action of Tanagel in the murine model of acute colitis by DSS. C57BL/6 mice were exposed to 2.5% Dextran Sodium Sulfate (DSS), given for 8 days in tap water. At the 5th, 6th, 7th, 8th day mice received 1 mg or 10 mg of TANAGEL by gavage in 200 ll of drinking water; control mice received water only. Body weight, occult blood test and stool consistency were measured every day and used to calculate the Disease Activity Index (DAI) to assess severity of colitis; survival was expressed as %. Mice were sacrificed at day 9 and colon length was measured, then colon was opened and underwent microscopical analysis to assess the degree of inflammation. To explore the direct effects of Tanagel on intestinal epithelial cell proliferation, an MTT assay was used on CT26 and Caco2, a murine and human intestinal epithelial cell line, respectively. TNF –a pretreated cells were incubated in presence of TNF-a (25 ng/mL) or Tanagel (5, 10, 50 lg/ml) and cell vitality was evaluated after 48 hours. Results: Tanagel significantly reduced DAI in treated mice compared to controls in a dose dependent manner, being 10 mg more efficacious than 1 mg dose. No differences were assessed between the three groups about body weight loss. Neither differences in mortality were observed. At the sacrifice the length of colons was measured. Gelatine Tannate treated mice showed a longer colon, compared to controls. Tanagel did not significantly affect the proliferation of Caco2 and CT26 at MTT assay. Proliferation was reduced at higher (no physiological) concentrations. Conclusion: Taken together our preliminary observation suggest that Tanagel decreased the clinical severity of colitis in mice. Gelatin

S287 tannate is an interesting product able to re-establish intestinal homeostasis in course of acute colitis as shown by human studies. Further analysis are required to better define mechanisms of action underlying these findings and more indication for gelatin tannate could be developed following specific studies.

Improving diagnostic accuracy in celiac disease diagnosis: antiendomysium antibody assay in the culture medium of duodenal biopsies P. Mansueto1, A. Carroccio2, A. D’Alcamo1, G. Ambrosiano1, A. Seidita1, F. Adragna1, A.M. Patti1, L. Di Prima1, G. Pirrone1, I. Pepe1, S. Di Rosa3, G.M. Rini1 1

Dipartimento di Medicina Clinica e delle Patologie Emergenti, Universita` di Palermo; 2Ospedali Civili Riuniti di Sciacca (AG); 3 Azienda Ospedaliera Villa Sofia-Cervello, Palermo, Italy Background and Aims: Celiac disease (CD) diagnosis is becoming more difficult as patients with no intestinal histology lesions may also be suffering from CD. The aim of the study was to evaluate the diagnostic accuracy of anti-endomysium (EmA) assay in the culture medium of intestinal biopsies for CD diagnosis. Patients and Methods: The clinical charts of 418 CD patients and 705 non-CD controls who had all undergone EmA assay in the culture medium were reviewed. Results: EmA assay in the culture medium had a higher sensitivity (98% vs 80%) and specificity (99% vs 95%) than serum EmA/antitTG assay. Furthermore, during the follow-up, four patients with negative serum EmA/anti-tTG, normal villi architecture and positive EmAs in the culture medium, developed villous atrophy and underwent gluten-free diet with consequent resolution of the symptoms and complete intestinal histology recovery. Conclusion: EmA assay in the culture medium should be included in the diagnostic criteria for CD diagnosis in ‘‘seronegative’’ patients.

Food hypersensitivity-associated irritable bowel syndrome: may fecal assays improve diagnosis? P. Mansueto1, A. Carroccio2, M. Soresi1, A. D’Alcamo1, G. Ambrosiano1, A. Seidita1, F. Adragna1, A.M. Patti1, L. Di Prima1, G. Pirrone1, I. Pepe1, S. Di Rosa3, G.M. Rini1 1

Dipartimento di Medicina Clinica e delle Patologie Emergenti, Universita` di Palermo; 2Ospedali Civili Riuniti di Sciacca (AG); 3 Azienda Ospedaliera Villa Sofia-Cervello, Palermo, Italy Background and Aims: A percentage of patients with irritable bowel syndrome (IBS)-like symptoms suffer from food hypersensitivity (FH) and improve on elimination diet. No assays have satisfactory sensitivity in identifying FH patients. The Aim of the study was to evaluate the frequency of FH diagnosis in IBS-like patients. To calculate sensitivity, specificity and diagnostic accuracy of fecal assays (tryptase, ECP and calprotectin) for FH diagnosis. Patients and Methods: 160 IBS patients were included. Elimination diet and double-blind placebo-controlled challenge were performed for FH diagnosis. Fecal assays and specific IgE were performed at the entry in the study. Results: 40 of 160 IBS patients (25%) suffered from FH. Fecal ECP and tryptase values were significantly higher in FH than in IBS notrelated to FH patients. ECP was the most accurate assay in FH diagnosis: sensitivity 65%, specificity 91%.

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S288 Conclusions: A large percentage of IBS patients really suffer from FH. In these patients tryptase and ECP are among the pivotal mediators of the inflammation. Fecal assays of ECP can be useful in identifying FH patients among IBS-presenting subjects. Fulminant hepatic failure: a rare and lethal cause L. Matarazzo, G. De Matteis, M. Montalto, A. Favuzzi, F.M. Vecchio, A.M. De Gaetano, M. Pompili, R. Landolfi Istituto di Medicina Interna, Dipartimento di Medicina Interna e Scienze Mediche Specialistiche, Universita` Cattolica del Sacro Cuore, Roma, Italy A 29 year old woman with congenital IgA deficiency came to our attention in August 2010 with a 5-month history of abdominal pain, sometimes associated with high fever. Physical examination showed cutaneous and scleral jaundice, On admission, liver function tests revealed total bilirubin of 13.64 mg/dl (normal, 30-20 mg/dl), aspartate aminotransferase 52 IU / l (normal, 7-45 IU/l), alkaline phosphatase 373 IU/l (normal, 98-279 IU/l), PT 32.0 s (normal, 70-125 s.), APTT 61.5 s (normal, 20.00-39.00 s) and platelets 24,000/cm3 (normal, 140-450/cm3). Hepatitis viral markers were all negative. There was no positive family history nor exposure to unusual environmental agents. At first, 5 month before, an ultrasound scan had demonstrated right hydronephrosis. Therefore, she was treated with courses of antibiotics, analgesic and antispasmodic therapy with little benefit. A subsequent contrast enhanced abdominal CT showed a widespread heterogeneity of hepatic parenchyma, partial portal vein thrombosis, signs of portal hypertension and confirmed right hydroureteronephrosis. Then, the patient was hospitalized in another hospital where an abdomen MRI was performed and was considered suggestive of a possible autoimmune hepatitis with microangiopathic changes and/or multiple small liver abscesses. The patient was treated with antibacterial drugs and, because of an urinary tract infection due to Candida Albicans, with courses of intravenous antifungal therapy owing to temporary resolution of the fever associated with deterioration of liver function: total bilirubin 10.44 mg/dl, direct bilirubin 3.40 mg/dl, INR 2.38. During hospitalization at our department, in suspicion of multiple liver abscess, several blood samples and two ultrasound-guided fineneedle aspirations of liver lesions with negative cytological and microbiological result were performed. The search for non organ specific autoantibodies and the dosage of the enzyme glucocerebrosidase on liver tissue resulted negative allowing to rule out autoimmune hepatitis and Gaucher’s disease. The contrast-enhanced abdominal CT scan showed multiple hypervascular liver lesions at the periphery, with central hypodensity due to necrosis. Abdomen MRI, confirmed this datum demonstrating an increased number and volume of peripherally hypervascular hepatic lesions most of which showed central necrosis but appeared isointense during hepatobiliary phase; similar lesions were also observed in the spleen. The alphafetoprotein was in the normal range and the transvaginal ultrasound, performed to exclude gynecological malignancy, was negative The liver function tests including coagulation parameters were severely worsened but, in order to confirm the clinical suspicion of an aggressive liver malignancy, the patient underwent a new ultrasound-guided percutaneous liver biopsy performed on one of the hypervascular lesion with a cutting needle The histological examination of the biopsy sample showed multiple small fragments of tissue constituted by elements with neoplastic proliferating hyperchromatic nuclei and irregular vascular lumen, showing immunoreactivity for CD34 and high

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 proliferative activity, highly suggestive of angiosarcoma. Brain CT showed hemorrhagic brain metastases. Unfortunately, the patient was beyond any possible treatment described in the literature for this disease, and died a few days after. Primary angiosarcoma of the liver is a rare disease with very limited treatment options, and the majority of patients die within 6 months of diagnosis. Surgery has a limited role due to the advanced stage at which these tumours are usually diagnosed. The patients who have been transplanted incidentally have not shown any survival benefit. The role of chemotherapy and the treatment with new techniques like transcatheter arterial chemoembolization has been described with very limited improvement in overall length of survival [1, 2]. References 1. Maluf D, Cotterell A, Stravitz T, et al. Hepatic angiosarcoma and liver transplantation: case report and literature review. Transplant Proc. 2005; 37:2195–9. 2. Bhati CS, Bhatt AN, Starkey G, Hubscher SG, Bramhall SR. Acute liver failure due to primary angiosarcoma: a case report and review of literature. World J Surg Oncol. 2008 Sep 30;6:104.

Autoimmune atrophic gastritis: prevalence, clinical presentation and clues to its diagnosis E. Miceli, S.M.T. Durante, M.V. Lenti, D. Padula, V. Imbesi, C. Vattiato, M. Di Stefano, G.R. Corazza 1st Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Italy Background & Aim: Autoimmune atrophic gastritis (AAG) is an immune mediated chronic inflammation that involves the gastric body and fundus leading to hypo-achloridria and vitamin B12 deficiency. Data on clinical presentation and pattern of autoimmune atrophic gastritis (AAG) are still few and fragmentary. Thus, the aim of this study was to assess a more detailed analysis of the demographic and clinical features of AAG patients. Patients and Methods: Clinical data and family history of 76 consecutive patients with AAG were recorded and analyzed. Diagnosis was based on histological ground according to the Sydney-Huston classification and on the positivity of antiparietal cells antibodies. Results: In the period 2007-2010, 2122 patients had their first evaluation in a gastroenterology outpatient clinic. At the end of their evaluation, 76 patients (3,6%) (ratio F:M 2,8:1, mean age 58 ± 18 years, range 15-82 years), met the diagnostic criteria for AAG. The most frequent abnormality (48.7%, N = 37) leading to diagnosis was related to vitamin B12 deficiency (macrocytic anaemia, macrocytosis without anaemia, anisocytosis, pancytopenia). The remaining patients were diagnosed because of an incidental endoscopic and histological evidence of atrophic body gastritis (40.8%, N = 31), family history of AAG (3,9%, N = 3), autoimmune screening for other conditions (3,9%, N = 3) and ataxia (2,6%, N = 2). Conclusions: AAG is reported as a rare condition but it may be often underdiagnosed due to the overlook of its systemic clinical manifestations. Our results show that AAG turned out to be a frequent condition in a setting of a tertiary referral gastroenterology outpatient clinic. Attention should be paid, particularly in middle age women, to haematological signs, endoscopic features, family history, autoimmune associations and neurological manifestations.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392

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The impact of anxiety on lactose intolerance symptoms V. Ojetti1, F. Bertucci1, G. Ianiro1, A. Tortora1, F. Buccelletti2, V. Gerardi1, D. Ferrarese1, E. Scarpellini1, M. Gabrielli2, G. Gigante1, A. Gasbarrini1 1

Internal Medicine and Gastroenterology, Gemelli Hospital, Rome; Emergency Medicine, Gemelli Hospital, Rome, Italy

2

Introduction: Lactose malabsorption is not always associated with lactose intolerance (LI). The factors responsible for symptom onset are not yet completely known. Visceral sensitivity may play a role in the pathogenesis of functional symptoms. A significant amount of clinical and research data suggest the importance of the brain-gut interaction in intestinal bowel syndrome. Aims & Methods: We aimed to evaluate the impact of anxiety on LI symptoms. A lactose breath test (LBT) was carried out in 104 (85F; mean age 44 ± 16 yrs) consecutive patients (pts) who referred to our Gastroenterology Unit for suspected LI. Abdominal symptoms (bloating, flatulence, pain, diarrhea) were evaluated using the visual analogue scale (VAS:0-10) throughout the LBT. All pts filled in the Hospital Anxiety and Depression Scale to determine anxiety. Statistical analysis was carried out using STATA 11 (Texas, USA). Results: 67.3% (70/104) pts resulted positive to LBT. 47% (49/104) pts resulted anxious (A) ([10 items). In A pts we did not find any difference in LI symptoms regardless the LBT results. The predominant symptoms reported in the A pts was bloating. Meanwhile NA pts with a positive LBT revealed a significant higher score of all LI symptoms compared to negative ones (table).

Symptoms

Ansia score BT_Cat

Bloating

0

Flatulence

0 0

\0.05

New investigational tools to assess and improve reflux symptoms in a cohort of singers, a specific professional group

ns

C. Papa1,2, L. Bonfrate1, N. Quaranta2, V. Di Nicola2, P. Portincasa1

2,1581 1,74813

BT Neg 0,93

1,75018

BT Pos

1,30358

0,92

BT Neg 1,0222 1,96405 BT Pos

Diarrhea

Std. Dev p

BT Neg 1,6444 2,05 BT Pos

Abdominal pain 0

Mean

1

\0.05

1,6325 2,19512

BT Neg 0

0

BT Pos

0,25

0,06

not of lactose malabsorption as assessed by lactose breath test (LBT) positivity. Visceral hypersensitivity, together with anxiety and somatisation, seems to play a role in different abdominal symptoms’ intensity as reported by pts during LBT. Aims & Methods: We aimed to assess the possible correlation between gas production during LBT and the intensity of gastrointestinal symptoms in anxious (A) and non-anxious (NA) pts. A H2/ CH4 LBT was carried out in 104 (19M, mean age 44.5 ± 16 yrs) consecutive pts referring to our Gastroenterology Unit for suspect LI. Abdominal symptoms (bloating, flatulence, pain, diarrhoea) were evaluated using a validated visual analogue scale (VAS) throughout the LBT. All pts also filled in the Hospital Anxiety and Depression Scale (HADS) for anxiety. Results are expressed as mean ± SEM. Correlations were assessed using Spearman RHO test (p \ 0.05). Statistical analysis was carried out with STATA 11 (Texas, USA). Results: Forty-three pts resulted NA (HADS \7 items). In A pts we did not find any significant correlation between mean gas levels and mean abdominal LI symptoms scores throughout LBT. Interestingly in NA pts there was a significant correlation between mean H2 concentration (30 ± 4 ppm) and bloating (p \ 0.015), pain (p \ 0.01) and flatulence (p \ 0.028) at 120 min from the start of LBT; diarrhoea scores significantly correlated with 40 ± 3 ppm H2 (p \ 0.017) at 120 min from the start of LBT. The CH4 producers, failed to correlate with any of the symptoms’ scores analysed. Conclusion: LI symptoms in A pts did not correlate with gas production neither H2 or CH4. Meanwhile in NA subject, LI symptoms increase according to the H2 production. H2 concentrations higher than 30 ppm, a value also indicative of sugar malabsorption, seem to be also indicative of LI if these preliminary results will be confirmed by larger studies.

Clinica Medica ‘‘A. Murri’’, Dipartimento Medicina Interna Medicina Pubblica; 2Clinica Otorinolaringoiatrica, Policlinico, Universita` degli Studi di Bari, Italy

\0.01

Conclusion: Anxious status significantly influence the severity of all LI symptoms. In A pts the presence of LI symptoms do not strictly correlate with a positive LBT. On contrary the presence of LI symptoms in NA pts may predict a positive LBT. In particular adjusting for the anxiety level diarrhoea seems to be the most significant symptoms related to LBT results.

Correlation between gas production and intensity of gastrointestinal symptoms during lactose breath test V. Ojetti1, A. Tortora1, G. Ianiro1, F. Bertucci1, F. Buccelletti2, V. Gerardi1, D. Ferrarese1, E. Scarpellini1, M. Gabrielli2, M. Campanale1, A. Gasbarrini1 1

Internal Medicine and Gastroenterology, Gemelli Hospital, Rome; Emergency Medicine, Gemelli Hospital, Rome, Italy

2

Introduction: Lactose intolerance (LI) is defined by the occurrence of different abdominal symptoms after milk ingestion in presence or

Background: Gastro-esophageal reflux disease (GERD) is a frequent disorder comprising a spectrum of typical esophageal symptoms (heartburn, chest pain, regurgitation) or atypical extra-esophageal symptoms (extra-esophageal reflux disease, EERD or laryngopharyngeal reflux, LPR) such as chronic cough, laryngitis, hoarseness, voice disorders and asthma. GERD symptoms might heavily affect the professional performance of singers, but the ultimate impact in this group of professionals remains poorly understood, so far. Aims: To assess the interaction between GERD symptoms, lifestyles in a cohort of professional singers. Methods: 20 singers with GERD symptoms (M:F = 5:15, both mean age 29 ± 14 SD yrs) were matched with 20 healthy subjects (M:F = 5:15, age 30 ± 4 yrs and 28 ± 1 yrs). All singers underwent a laryngoscopy at baseline and after 6 mo. to determine the prevalence of laryngeal irritation signs (Reflux Finding Score-RFS) and an interview by Reflux Symptom Index (RSI plus Visual Analogue Scale-VAS 0-100 mm) exploring reflux perception, dysphonia, personal strategies related to exhibition and subjective perception of GERD-related well-being. Both singers and controls were also explored for dietary-lifestyle habits, ‘‘junk food’’ consumption (‘‘MedStyle’’ questionnaire). Singers underwent an extensive 6 mo. reeducational program with general anti-GERD and specific lifestyle

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S290 modifications (including promotion of salivation by oral water spray a/o wet tissues under the nostrils). Results: In singers (M vs. F), BMI (Kg/m2) was 25.9 ± 5.1 vs. 25.0 ± 4.8, (P = NS), abdominal girth (cm) by IDF was 91.2 ± 15.3 vs. 92.4 ± 13.9 (P = NS), by ATP III was 90.6 ± 12.4 vs. 92.1 ± 12.0, (P = NS). In healthy subjects BMI was 23.9 ± 4.0 vs. 20.5 ± 1.9 (P \ 0.01), abdominal girth by IDF was 82.8 ± 1.8 vs. 78.4 ± 6.7, (P = NS), by ATP III was 84.6 ± 3.9 vs. 84.3 ± 5.9 (P = NS). Whereas BMI (P = 0.006) and abdominal girths (IDF, P = 0.002 and ATPIII, P = 0.032) were greater in F singers than F controls, basal metabolic rate and daily caloric intake were comparable between singers and controls (1538 ± 210 and 1474 ± 209 kcal/d, resp.; 1660 ± 510 and 1708 ± 303). Intake of junk food was greater in singers than controls (7-items JUNK-SCORE 15.3 ± 8.2 vs. 4.45 ± 0.9, P = 0.001). Percent of alcohol consumers, weekly alcohol intake and alcoholic Kcal were significantly greater in singers than controls (65% vs. 25%, P = 0.025; 51.5 ± 75.8 vs. 11.4 ± 16.4 g/wk, P = 0.026; 425.2 ± 591.7 vs. 99.9 ± 140.0 kcal/ wk, P = 0.022, respectively). Smokers were less in singers (15% vs. 55%, P = 0.02). At baseline, the prevalence of symptoms in singers was 85% for heartburn before vocal exhibition, 70% for morning dysphonia, 100% for recurrent dysphonia (one or more episodes of dysphonia lasting at least 5 days in 3 mo.), 80% for vocal dryness. Moreover, 70% of singers remained fasting and 85% took acid-suppressive medications before exhibition. Symptoms improved after 6 mo. reeducation, RFS decreased from 3.6 ± 2.0 to 1.2 ± 1.0 (P \ 0.001) indicating improved laryngoscopy signs, while wellbeing (RSI-VAS) increased from 39.0 ± 7.2 to 70.2 ± 15.2 mm after 6 mo. (P \ 0.001). Conclusions: The professional category of singers deserves a careful anthropometric, metabolic and lifestyle survey in relation also to esophageal and extraesophageal GERD. A simple reeducation programme leads to improved laryngeal GERD signs and could increase the compliance and the well-being of singers, avoiding unnecessary investigations and therapies. Alimentary lifestyle questionnaire appears as a novel investigational tool to assess, in a group of specific professional figures as singers, bad alimentary habits, which may provoke reflux symptoms, and to follow up subjects in the management and prevention of GERD and dyspeptic disorders.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 is well known that prognosis in patients with type 1 HRS is worse than indicated by Model of End-stage Liver Disease (MELD) score, up to now, neither type 1 HRS nor the need of a long-term treatment have been considered as an exception to MELD in liver allocation policy. In addition, paradoxically, the response to treatment with terlipressin and albumin, lowering serum creatinine, reduces the MELD and could delay the time of LT. Methods: We describe our experience of long-term administration of terlipressin as a bridge to LT in three patients with cirrhosis and continuous recurrence of type 1 HRS. For the purpose of this report we define as continuous recurrence of type 1 HRS a relapse of type 1 HRS more than once within 72 h after the discontinuation of treatment. For all three patients we requested an ‘‘early transplant’’ which is an option recognized in our country to reduce waiting times for LT. Results: These three cases were observed among a cohort of 24 consecutive patients admitted for type 1 HRS in our Liver Unit (12.5%). These three patients represent also the 60% of those with recurrent type 1 HRS after the withdrawal of treatment. All three patients were transplanted within 2 months of onset of HRS. All patients are still alive, none of them required renal replacement therapy, none of them developed chronic kidney disease. Conclusions: Our experience suggest that continuous recurrence of type 1 hepatorenal syndrome is not a rare event and that long-term treatment with terlipressin and albumin is effective and well tolerated in these patients. The long-term treatment could delay the time for LT and, therefore, should be considered as a priority criterion in the allocation system in LT. This can be made either by considering the baseline MELD, that was evaluated before the start of treatment of type 1 HRS, or including the long-term treatment of type 1 HRS in the calculation of MELD score as already provided for renal replacement therapy.

Immune thrombocytopenic purpura and Kaposi’s sarcoma after liver transplantation: a challenge for the management of immunosuppressive therapy S. Piano1, G. Segato1, S. Fasolato1, A. Romano1, M. Cavallin1, F. Morando1, U. Cillo2, A. Gatta1, P. Angeli1 Department of Clinical and Experimental Medicine; 2Department of Gastroenterology and Surgical Sciences, University of Padova, Italy 1

Continuous recurrence of type 1 hepatorenal syndrome and longterm treatment with terlipressin and albumin: a new exception to MELD score in the allocation system to liver transplantation? S. Piano1, F. Morando1, S. Fasolato1, M. Cavallin1, A. Romano1, G. Zanus2, U. Cillo2, A. Gatta1, P. Angeli1 Department of Clinical and Experimental Medicine; 2Department of Gastroenterology and Surgical Sciences, University of Padova, Italy 1

Background: Type 1 hepatorenal syndrome (HRS) is a severe complication of liver cirrhosis with a highly negative impact on prognosis. The optimal and definitive treatment of HRS is liver transplantation (LT). The administration of terlipressin and albumin has been shown to be effective in the treatment of type 1 HRS. A good response to this treatment is associated with an improvement of both transplant free survival and outcome of liver transplantation. Nevertheless, type 1 HRS can recur in up to 20 % of responders after the discontinuation of the treatment. It has been stated that the recurrence of type 1 HRS can be reverted with a re-treatment with terlipressin and albumin. Subsequent recurrence of type 1 HRS may require long-term treatment with terlipressin and albumin. Although it

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Introduction: Thrombocytopenia is common among liver transplant candidates. The pathogenesis of this phenomenon is complex, and splenic pooling, increased platelet consumption and/or impaired production have been variably suggested to contribute as etiologic factors. Several mechanisms may potentially account also for thrombocytopenia after liver transplantation (LT). Post-transplant thrombocytopenia has been attributed mainly to decreased platelet production, increased platelet consumption, or infections. Pre-existing hypersplenism also makes an important contribution, because the spleen gradually shrinks over a period of months, and up to a year after OLT, until a normal portal pressure can be restored. A severe thrombocytopenia after LT is rarely due to immunologically mediated destruction of the platelets. In fact, transplanted organs, particularly livers and kidneys, carry passenger lymphocytes that can transmit autoimmune diseases or initiate alloimmune disorders in the recipient. In the whilst immunosuppression cannot prevent the onset of autoimmune diseases. Case report: We report a case of a 61 years old patient admitted to our Liver Unit on February 2011 for purpura and severe thrombocytopenia (7.000/mm3). He received a liver transplantation (LT) on

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 May 2010 because he was suffering from hepatocellular carcinoma and alcoholic cirrhosis. The platelet count at the time of LT and two months later were 66.000/mm3 and 62.000/mm3 respectively. On October 2010 purple nodules appeared in the leg and a biopsy showed Kaposi’s sarcoma (KS). KS was effectively treated reducing immunosuppression (achieving a serum concentration of tacrolimus &4 lg/l and adding low dose everolimus). On January 2011 platelet count had fallen to 35.000/mm3. At that time, physical examination showed a moderate splenomegaly and cutaneous purpura. Remission of Kaposi’s sarcoma was seen. Everolimus and trimethoprim-sulfamethoxazole were discontinued without clinical improvement in the subsequent 10 days. Liver donor had no history of thrombocytopenia at the time of transplantation. Serologies were negative for HIV, parvovirus B19, HCV. Polymerase chain reaction was negative for CMV and EBV. Helicobacter Pylori stool antigen test was negative. ANA, antiphospholipid antibodies and lupus anticoagulant were negative. Antiplatelet antibodies (anti glycoprotein IIb-IIIa) was positive and bone marrow biopsy revealed megakaryocytes present in increased numbers excluding in a definitive way a myelosuppression. On the basis of all these data, we made diagnosis of immune thrombocytopenic purpura (ITP) and started promptly therapy with Methylprednisolone 2.5 mg/kg/day for seven days and intravenous immunoglobulin (IVIg) 1 g/kg/day for two days. Purpura and platelet count progressively improved. Corticosteroid therapy was tapered and shifted to prednisone 25 mg daily. There was no recurrence or progression of KS. On may 2011 he was in good clinical condition and platelet count was 103.000/mm3. Conclusion: Immune thrombocytopenic purpura is a relatively rare and life-threatening cause of thrombocytopenia in liver transplant recipients (0.7%). Kaposi’s sarcoma has been also described after LT (0.84%). An association between ITP and KS can occur in the setting of immunodeficiency, mainly in HIV infection, as well as during immunosuppression. Nevertheless, to the best of our knowledge this is the first description of an association between ITP and KS in a liver transplant recipient.

Conditional survival after hepatic resection for hepatocellular carcinoma in cirrhotic patients F. Piscaglia1, A. Cucchetti2, M. Cescon2, G. Ercolani2, E. Terzi1, L. Bolondi1, M. Zanello2, A.D. Pinna2 1

Department of Internal Medicine, University of Bologna, Italy; Liver and Multiorgan Transplant Unit, University of Bologna, Bologna, Italy

2

Survival estimates are commonly reported as actuarial survival since first observation, but future survival probabilities can change over time. Conditional survival (CS) is a measure of prognosis for patients who have already survived some times such years since diagnosis; however, data on CS for cirrhotic patients, resected for hepatocellular carcinoma (HCC), are lacking. Clinical data of 300 consecutive cirrhotic patients who underwent HCC resection in a tertiary care setting, were reviewed and the actuarial survival appropriately estimated. The 5-year CS was calculated as CS = S(x + 5)/S(x) and represents the probability of surviving an additional 5 years, given that the person has already survived x years. The 3-, 5-, and 10-year survival rates were, respectively, 69.2%, 57.7% and 25.3%, and were, as expected, lower in the presence of: 1)

S291 clinical signs of portal hypertension; 2) Model for End-stage LiverDisease (MELD) score C9; 3) United-Network for Organ-Sharing T3tumor; 4) G3-G4 tumors and 5) microscopic vascular invasion. however, five-year CS calculation showed that patients resected for more advanced (T3 stage) tumors or with adverse histological features will experience the same survival probabilities as patients with less advanced tumors or favorable histological features from the third year after surgery onwards, since they had probably escaped recurrence from intrahepatic metastases; conversely, portal hypertension and MELD score did not influence CS as cirrhosis cannot be adequately cured. Patients who underwent repeated hepatectomy for tumor recurrence showed longer CS. CS showed that the impact of different variables influencing survival is not linear overtime after hepatic resection. Information derived from CS can be utilized to better manage HCC patients, including the potential future setting of adjuvant therapies and support the choice of not listing for transplantation resected patients not recurring within the first 2 years.

Treatment of HCV compensated cirrhotic patients is equally effective before and after liver transplantation F.R. Ponziani1, B.E. Annicchiarico1, M. Siciliano1, M. Pompili1, G. Gasbarrini2, A. Gasbarrini1 1 Internal Medicine and Gastroenterology, Catholic University of Rome; 2Fondazione Ricerca in Medicina, Italy

Introduction: Response to combined antiviral treatment has been reported to be lower in patients with hepatitis C virus (HCV)-related cirrhosis if compared with non-cirrhotics. However, treatment is recommended to avoid decompensation and complications, and to prevent graft reinfection after liver transplantation (LT). Similarly, patients developing HCV-related cirrhosis after LT should be treated to avoid graft loss, even if a lower rate of response and tolerability have been reported. Aims & Methods: To report the differences in tolerability and response to treatment in a retrospective series of compensated HCVcirrhotic patients before and after LT. 43 HCV-cirrhotic patients (mean age 55.2 ± 8.9, 65.1% male, 34.9% female, Child-Pugh class A, genotype 1: 58.1%, 2: 30.2%, 3: 4.7%, 4: 7%) and 17 LT patients with recurrent HCV-related cirrhosis (mean age 57.4 ± 9.1, 88.2% male, 11.8% female, Child-Pugh A, genotype 1: 64.7%, 2: 17.6%, 3: 5.9%, 4: 11.8%) were included in the analysis. Among LT and nonLT cirrhotics, 37.2% and 47.1%, respectively, previously received an unsuccessful treatment. All patients received recombinant or pegylated interferon plus ribavirin at standard dose and duration. No stopping rule was adopted for LT patients. Results: An early virological response (EVR) was reported in 30/43 (69.8%) non-LT and in 8/17 (47.1%) LT HCV cirrhotic patients, a sustained virological response (SVR) in 18/43 (41.9%) and 8/17 (41.1%), respectively. No statistical difference in EVR and SVR rates between the two groups was observed. In the group of LT patients, only one without EVR subsequently achieved SVR. Among HCV non-LT cirrhotics, 6/43 (13.9%) patients prematurely discontinued the treatment 4/43 (9.3%) due to adverse events (fatigue, intolerance, HCC, polytrauma); 8/17 (47%) among LT cirrhotics withdrew the treatment, 4/17 (23.5%) due to adverse events (anemia, leucopenia, encephalopathy) the remnants for lack of response. No statistical difference in the rate of discontinuation of the two groups

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was observed. Side effects experienced during the treatment are shown in Table 1. Table 1 Non-LT cirrhotics (43)

LT cirrhotics (17)

3/43 (6.9%)

0

– Grade 1 – Grade 2

12/43 (27.9%) 2/43 (4.6%)

0 4/17 (23.5%)

– Grade 3

0

2/17 (11.7%)

– Grade 2

0

2/17 (11.7%)

– Grade 3

6/43 (13.9%)

1/17 (5.8%)

Intolerance (fatigue, flu-like symptoms, depression) Anemia

Neutropenia

Conclusion: HCV antiviral treatment is equally effective and tolerated in compensated cirrhotics both before and after LT.

Observe, think, do not act: two cases of PVT spontaneous resolution in cirrhotic patients F.R. Ponziani1, B.E. Annicchiarico1, M. Siciliano1, A. De Gaetano2, M.A. Zocco1, G. Gasbarrini1-3, A. Gasbarrini1 Internal Medicine and Gastroenterology; 2Radiology, Catholic University of Rome, Rome; 3Fondazione Ricerca in Medicina, Italy

1

Introduction: Portal vein thrombosis (PVT) prevalence among cirrhotic patients ranges between 4.4 and 15%, 6.5% in presence of hepatocellular carcinoma (HCC). Anticoagulants even if, in cirrhotic patients, their use has not yet been recommended. Spontaneous PVT resolution has been rarely described; only one case due to acute pancreatitis has been reported in a patient with cirrhosis and HCC. Aims: We describe PVT spontaneous resolution in two cirrhotic patients, admitted to our hospital. Case report: PT1 64-year-aged woman affected by HCV-related liver cirrhosis (CHILD-Pugh C11, MELD 17), was admitted for severe ascites and hyponatremia. PT2, 67-year-aged man affected by HCV-related liver cirrhosis (CHILD-Pugh A6, MELD 11) and multifocal HCC (BCLC B) previously treated with TACE (partial response, mRECIST), was admitted for gastrointestinal bleeding from esophageal varices. PVT evaluation was performed by CT scan. PT2 presented a massive neoplastic thrombosis extended to the PV right and segmentary branches and to the confluence (fig. 1a), while in PT1 PVT was extended to the right branch and to the confluence (fig. 1b). Due to patients’ clinical conditions, anticoagulant treatment was deferred. Spontaneous complete PV patency was observed after 1 month for PT1, while a partial recanalization was observed after 3 months for PT2 (Fig 1 c, 1 d), with significant improvement in patients’ clinical conditions (resolution of ascites and no further episodes of bleeding, respectively). Conclusions: Although a few literature data are still available, according to our experience PVT spontaneous resolution is a rare but possible event in cirrhotic patients, even in presence of HCC.

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Gastrointestinal (GI) motorfunction and symptoms in a novel cluster of patients with familial mediterranean fever (FMF) living in Apulia and Basilicata, Italy P. Portincasa1, V. Ruggiero1, L. Bonfrate1, G. Scaccianoce2, D. Piglionica2, C. Bozzao3, R. Bagnulo3, N. Resta3, G. Palasciano1 1 Clinica Medica ‘‘A. Murri’’, DIMIMP, Universita` degli Studi di Bari; 2Endoscopia Digestiva, Osp. Umberto I, Altamura, Bari; 3 Genetica Medica, Dipartimento di Biomedicina Eta` Evolutiva, Universita` degli Studi di Bari, Bari, Italy

Background: FMF is a disorder characterized by sporadic, paroxysmal attacks of fever and serosal inflammation. It is inherited as an autosomal recessive trait and has been described primarily in several ethnic groups originating in the Mediterranean littoral — Sephardic Jews, Armenians, Turks, North Africans, Arabs, and less commonly Greeks and Italians. The FMF gene (MEFV) is located on the short arm of chromosome 16 (cr16p), which encodes a 781 amino acid protein (‘‘pyrin’’ or ‘‘marenostrin’’), expressed almost exclusively in the cytoplasm in cells of myeloid lineage (among circulating cells). Marenostrin acts as intranuclear regulator of peptides involved in inflammation (inflammasome) which upon activation, trigger the release of IL-1 beta and are mediators of apoptosis. Over 50 disease-associated mutations in MEFV have been identified. Lifetime therapy with colchicine in symptomatic subjects prevents painful attacks and amyloidosis as the most important complication, which puts patients at risk of end-stage renal failure. Aim: To report on FMF patients living in a specific geographical area, and to relate genetic and clinical features with GI motility. Methods: Starting from a first highly symptomatic young patient, we have so far detected 23 FMF patients (M:F = 11:12, mean age, 39.6 ± 16.3 and 39.3 ± 15.8 yrs ± SD, resp.). All patients underwent DNA analysis amplified by PCR and subjected to sequencing analysis of entire coding region of the MEFV gene. The clinical diagnosis of FMF was according to the Tel-Hashomer criteria. Because of the clear GI implication in FMF, gastric (antral areas, emptying time) and gallbladder (volumes, emptying time) motility (by 5.0 MHz functional ultrasonography, ClarUs, Telemed, Ltd), orocecal transit time (H2-breath test by Lactofan, Medimar &

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Italchimici, Italy) and GI perception (appetite, satiety, fullness and epigastric pain by visual-analogue scale) were assessed during fasting and postprandially (by the ingestion of 200 ml standard liquid meal Nutridrink, Nutricia) in between symptom attacks, every 5 minutes for 120 minutes. A sex- age- body size-matched healthy control group included 21 subjects (M:F = 10:11, age of 38.0 ± 9.0 and 38.2 ± 8.0 yrs, resp). Results: The majority of patients (16/23, 70%) originated from Altamura (a city south-west of Bari), 22% from Basilicata region, and 8% from the city of Bari. The following MEFV mutations were found in order of prevalence: 14 (61%) patients carried E148Q/R761H in compound heterozygous state, 6 patients (27%) carried K695R in heterozygous state, 1 patient (4%) carried E148Q in heterozygous state, 1 patient (4%) carried R202Q in heterozygous state and 1 patient (4%) carried R202Q and M694V mutations. Symptoms included both abdominal pain and fever (44%), joint pain (22%), fever alone (9%), fatigue (4%), erysipela-like erythema (4%) or no symptoms (17%). The mean age of FMF at onset of symptoms was 19 ± 8 yrs; clinical features included acute attacks, mean duration of one day, with a frequency of less or 1 episode/mo. (48%), 2 episodes/ mo. (22%), and more than 2 episodes/mo. (13% of cases). Of note, the time to final diagnosis of FMF was 15.4 ± 9.7 yrs. The study of gastric emptying showed comparable antral areas in fasting (basal 3.1 ± 1.6 vs. 3.8 ± 0.7 cm2 in controls, P = NS) and postprandially (max 14.3 ± 7.1 vs. 11.4 ± 1.6 cm2 in controls, P = NS) with delayed emptying (half emptying of 42.4 ± 11.7 vs. 24.9 ± 7.0 min in controls, P = 0.001). The study of gallbladder emptying showed comparable volumes in fasting (20.8 ± 10.7 vs. 22.8 ± 6.5 ml in controls, P = NS) and postprandially (residual volume 5.3 ± 1.8 vs. 6.6 ± 2.6 ml in controls, P = NS) with normal emptying time (20.3 ± 7.1 vs. 23.0 ± 5.8 min in controls, P = NS). Orocecal transit time was delayed in FMF (127.5 ± 52.7 vs. 88.3 ± 15.9 min, P = 0.02) without evidence of small intestinal bacterial overgrowth. GI perception was comparable between FMF and controls in the fasting state and postprandially. All FMF patients have responded to therapy with colchicine treatment (1 mg p.o./day), so far. Conclusions: A novel cluster of FMF patients is being characterized between Apulia and Basilicata with specific MEFV mutations. Main GI symptoms include fever & abdominal pain. One should be aware that the final diagnosis of FMF can be consistently delayed. Patients display a general GI slowdown without impairment of gallbladder motorfunction. The study of GI motility by noninvasive techniques might provide additional pathophysiologically relevant information of FMF during the natural history of this rare disorder.

Agreement and predictive validity of neurophysiological, psychometric and psychophysical indices of hepatic encephalopathy I.D. Raduazzo, S. Schiff, M. De Rui, D. Aprile, E. Balistreri, P. Angeli, A. Gatta, C. Merkel, P. Amodio, S. Montagnese Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy The quantification of hepatic encephalopathy (HE) relies on neurophysiological, psychometric and psychophysical variables. The aim of this study was to investigate the degree of agreement between such variables and their predictive value in relation to the development of HE-related hospitalisations. One hundred and seventeen consecutive cirrhotic outpatients were enrolled [83 (71%) males; mean ± SD age: 58 ± 11 yrs; 40 patients were classified as Child’s class A, 52 as B and 25 as C; 71 (61%) had a history of overt HE]. All patients underwent full neuropsychiatric assessment, EEG recording, paperand-pencil psychometry (PHES) and Critical Flicker Frequency

S293 (CFF). The EEG was analyzed spectrally, PHES scored according to age/education-adjusted Italian norms and CFF qualified as abnormal if B39 Hz. Sixty-three patients were followed up prospectively for an average of 8 ± 6 months in relation to the occurrence of death/transplantation and HE-related hospitalisation. On the day of study, 41 patients (35%) had mild overt HE; of these, five were unable to complete PHES and three to complete CFF. Of the patients with overt HE, 34/41 (83%) had an abnormal EEG, 23/36 (64%) had abnormal PHES and 21/38 (55%) had abnormal CFF. Along the same lines, patients with overt HE had worse average EEG (relative theta power: 47 ± 17 vs. 25 ± 15%, p \ 0.0001), PHES total score (-5.1 ± 3.9 vs. -0.7 ± 2.8, p \ 0.0001) and CFF (39 ± 5 vs. 42 ± 5 Hz, p \ 0.005) than patients with no clinical signs of HE. Of the remaining 76 patients, 18 (24%) had an abnormal EEG, 11 (14%) had abnormal PHES and 16 (21%) had abnormal CFF; 7 (9%) had more than one abnormal test. Patients with a history of overt HE had slower EEG (relative theta power: 37 ± 20 vs. 24 ± 15%, p \ 0.001) and worse PHES total score (-2.4 ± 3.6 vs. -0.9 ± 3.6, p \ 0.05) than their counterparts with no previous HE, while CFF was comparable in the two groups (41 ± 5 vs. 42 ± 5 Hz, n.s.). During follow-up, five patients died, 9 underwent OLTx and 17 had an HE-related hospitalisation. Both the EEG mean frequency (v2 = 7.1, b = -0.27 ± 0.1, p = 0.007) and the PHES total score (v2 = 5.4, b = -0.14 ± 0.05, p = 0.01) were predictors of the subsequent development of HE-related hospitalisation; in contrast, CFF was not. When the EEG and the PHES were included in the same model, only the EEG remained a significant predictor. In conclusion, the agreement between neurophysiological, psychometric and psychophysical measures of HE is poor and while all three variables have some degree of association with the disease, the EEG seems to be more strongly related than the other two to both previous and subsequent HE episodes.

Derangement of N-6/N-3 polyunsaturated fatty acids balance in patients with liver cirrhosis V. Raparelli1, L. Napoleone1, V. Giannella2, C. Lucidi2, R. Carnevale1, M. Saliola1, F. Angelico1, M. Merli2, O. Riggio2, S. Basili1 1

Divisione I Clinica Medica, ‘‘Sapienza’’ University of Rome, Rome; II Gastroenterologia, ‘‘Sapienza’’ University of Rome, Rome, Italy

2

Background: Hepatic fibrosis represents a wound healing response to injury that ultimately leads to cirrhosis. Experimental studies demonstrated that the liver is one of the organs that might be influenced by a derangement of n-6:n-3 polyunsaturated fatty acids (PUFA) ratio in terms of progression of chronic damage. Tumor necrosis factor alpha (TNF a) is a pro-inflammatory cytokine that is up-regulated in liver diseases and could potentially contribute hepatic fibrosis. Aims and Methods: To explore the behavior of PUFA balance and its relationship with TNFa in liver disease, we performed a cross sectional study in cirrhotic patients (n = 50) with different degrees of liver disease defined as low (class A), moderate (class B), or severe (class C) according to Child-Pugh (CP). Serum PUFA n-3 and Arachidonic Acid (AA), as well as TNFa, were measured and compared with a sex- and age- matched control group (n = 50). Results: Compared to controls, cirrhotic patients had lower serum levels of AA and n-3 PUFA [p \ 0.001], higher n-6/n-3 ratio and higher levels of TNFa [p \ 0.05]. Patients with higher n-6/n-3 ratio were more likely to have moderate or severe than mild liver failure [p \ 0.05]. N-6/n3 ratio significantly correlated with albumin levels (R = -0.41, p = 0.003), CP score (R = 0.30, p = 0.035), PT-INR (R = 0.32, p = 0.022) and TNF a (R = 0.34, p = 0.015). A multivariate regression analysis revealed that n6/n3 ratio was independently related to albumin serum levels (beta coefficient = -0.30, p = 0.0296) and TNFa serum levels (beta coefficient = 0.25, p \ 0.05).

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Conclusions: In liver cirrhosis the imbalance between n-6 and n-3 PUFA is associated with TNFa up-regulation as well as with liver disease impairment. These data warrant further study to evaluate if n-3 supplementation may reduce inflammation and eventually liver disease progression.

ISGs group. However, the inverse correlation between SOCS3 and IL28B in HCV patients opens a new scenario on the combined use of both genetic variants to predict the response after antiviral therapy.

Celiac disease and company M.G. Serra, G. Cassati, Y. Hadad, A. Piccinni, M. Polo, L. Sansone

Genetic predictors of response in the treatment of chronic hepatitis C virus infection 1

2

1

1

U.O.C. Medicina-Az.Osp. ‘‘Cardinale Panico’’, Tricase (LE), Italy 2

R. Russo , M.F. Svelto , A. Gambale , V. Rosato , M. Masarone , V. La Mura2, A. Iolascon1, M. Persico2 1

Ceinge Centro di Ingegneria Genetica e Biotecnologia Avanzate; Internal Medicine and Hepatology Second University of Naples, Naples, Italy

2

Background: The response to antiviral therapy of chronic hepatitis C virus (HCV) infection is determined by virological, environmental and genetic factors. In 2008, we identified a link between the response to antiviral treatment and the suppressor cytokine signaling 3 (SOCS3) gene, an inhibitor of the JAK-STAT pathway, which was overexpressed in non-responder (NR) patients with genotype 1b HCV (HCV-1) versus patients with genotype 2 HCV (HCV-not 1). SOCS3 expression has also been found to be increased in patients HCV-1 who did not respond to treatment. More recently, were found several highly correlated common single nucleotide polymorphisms (SNPs) in the neighborhoods of three IFN-k genes (IL29A, IL28A and IL28B) as predictors of response to antiviral therapy in HCV-1 patients. Among these, SNP rs12979860, upstream of the IL28B, was strongly associated with SVR (genotype CC), both among patients of European ancestry and African American patients. This association has been recently characterized in a cohort of genotype 2 or 3 patients. Aim and Methods: We analyzed the IL28B-SNP rs12979860 frequencies in a control (N = 50) and HCV population (N = 90, 46 HCV-1 and 44 HCV-2) from Italy, in order to correlate them with the viral genotype and the response to antiviral therapy. Moreover, we performed a correlation analysis between the gene expression of SOCS3 and IL28B in both populations. Results: IL28B-SNP rs12979860 allele frequencies in the control group (C allele = 69.0% and T allele = 31.0%) were similar with those observed in HCV population (C allele = 64.6% and T allele = 35.4%). We confirmed the association between CC genotype of HCV patients and SVR (CC = 50.9%, CT = 41.5%, TT = 7.5%; p = 0.01 for trend). The gene expression analysis performed on 89 HCV patients and from 45 healthy subjects showed that IL28B is induced by viral infection, as previously described. However, this induction seems to be mediated to a greater extent from the HCV-2 than HCV-1 (p = 0.003, Mann-Whitney). The gene expression analysis showed an opposite trend for SOCS3 expression between HCV-1 and HCV-2 patients (p = 0.000001, Mann-Whitney), confirming our previous reports. The correlation analysis performed on healthy subjects showed a direct correlation between SOCS3 and IL28B gene expression (Pearson’s correlation 0.38, p = 0.011). When we evaluated the correlation between SOCS3 and IL28B in HCV patients, we found an inverse correlation (Spearman’s correlation -0.26, p = 0.014). Conclusions: We confirmed the association between CC genotype and SVR, although our results seem to underestimate this association (50.9% vs &80%). Our observation about IL28B-SOCS3 correlation in healthy subjects is in agreement with previous studies, which have demonstrated that both INF1 and INF 3, stimulate the same pathway, i.e. JAK-STAT, leading to the up-regulation of a set of interferonstimulated genes (ISGs) (16,18). Of note, SOCS3 ranks right in the

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Introduction: The tendency to develop another disease in patients with previous history of an autoimmune disease occurs in about 25% of these patients, more women. Familial or genetic, infectious, immunologic, psychological factors have been implicated in the development of multiple autoimmune syndrome; certain autoantibodies are found in disorders affecting multiple organs. In many cases, the presence of one autoimmune disorder helps lead to the discovery of other autoimmune conditions. Case report: A woman 44-year-old was referred to our Medical Division showing since a year the persistent increase of transaminase (92), gammaGT (93), anaemia, weakness of nails and hair. Laboratory investigation included test for autoimmunity (ANA, antids DNA, anti- ENA, p-ANCA, c-ANCA, AMA, LKMA): negative. Positive anti-endomisio (EMA), anti-transglutaminase, anti gastric mucosa, anti smooth muscle (ASMA), anti-actine. Celiac disease was suspected. Oesophago-gastroduodenoscopy with biopsy was performed. Gastric biopsy:mild chorion lympho-plasmacell inflammation. Duodenal biopsy: lesion type 3C Marsh (changed).Hepatic biopsy: mild chronic hepatitis. HLA: DRB1: 04/11-DQ 02/03 positive. Celiac disease, autoimmune gastritis, autoimmune hepatitis type 1 (score [15) was diagnosed. The patient was dismissed with gluten free diet. In follow up the hyperthyroidism with anti-thyroid peroxidase (Ab-TPO) occurred. Autoimmune thyroiditis resulted in chronic thyroiditis with normal level of thyroid hormones. Duodenal biopsy at two years showed lesion type 1 Marsh (changed). In follow up transaminase value decreased, but alkaline phosphatase and gamma-GT value increased. The diagnosis of overlap syndrome autoimmune hepatitis-primary biliary cirrhosis was suggested. The adopted therapy was UDCA 12 mg/kg/day. The follow up at five years showed normal value of transaminase, alkaline phosphatise, gammaGT. Anaemia persist and the patient take periodic therapy with iron i.v., in addition to gluten free diet and UDCA. Discussion: The presence of one autoimmune disease merit the search for a second autoimmune condition. The occurrence of multiple autoimmune phenomena in this case indicates the need for continued surveillance for the development of new autoimmune disease. In celiac disease the alterations of intestinal barrier maybe is the cause of alteration of immune system. The normalization of intestinal barrier with gluten free diet is maybe the cause of normalization of hepatic function.

Impairment of TLR7-dependent signalling in dendritic cells from chronic hepatitis C virus (HCV)-infected non responders to interferon/ribavirin therapy O. Simone, C. Tortorella, B. Zaccaro, N. Napoli, S. Antonaci Dipartimento di Clinica Medica, Immunologia e Malattie Infettive, Sezione di Medicina Interna, Universita` degli Studi di Bari Background and Aim: Dendritic cell (DC) dysfunction has been suggested to play a role in the weak antiviral T-cell responsiveness

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 observed during the course of chronic hepatitis C virus (HCV) infection. This study was undertaken to evaluate whether changes in DC functions might be related to a different therapeutic outcome in HCV-infected patients. Methods Peripheral blood DCs (PBDCs) or monocyte-derived DCs (MoDCs) were obtained from chronic HCVinfected patients, responders (SVR) or non responders (NR) to interferon/ribavirin therapy, and from healthy controls (HC). The frequency of BDCA-1+, BDCA-3+ and CD16+ myeloid DCs (mDCs) and BDCA-2+ plasmacytoid DCs (pDCs), as well as the expression of the costimulatory molecule CD86 in each PBDC subset, were evaluated by flow cytometry. MoDCs from single individuals were stimulated with TLR2, 3, 4 and 7 ligands and analysed for CD86, CD83, CD40, CD80 and CD209 expression. Finally, MAPK phosphorylation of TLR7-triggered MoDCs was assessed by western blotting. Results: NR exhibited a reduced percentage of BDCA-1+ mDCs, as well as lower levels of CD86+ cells, in both BDCA-1+ mDCs and pDCs as compared to SVR and HC. Furthermore, MoDCs from NR displayed a defective CD86 and CD83 increase and ERK1/2 or p38MAPK phosphorylation upon TLR7-cell triggering. Conclusions Our data suggest that a TLR7-dependent impairment of costimulatory molecule expression caused by HCV persistence may affect DC activity in NR patients.

Assessment of adrenocortical reserve in stable patients with cirrhosis T. Tomaselli, G. Privitera, G. Fede, L. Spadaro, A.K. Burroughs, F. Purrello. U.O.C. di Medicina Interna Dipartimento di Biomedicina Clinica e Molecolare Universita` di Catania Ospedale Garibaldi Nesima, Catania, Italy Background & Aims: Adrenal insufficiency (AI) is reported in critically ill patients with cirrhosis and is associated with increased mortality. It is unclear if AI is an underlying condition or triggered by critical events (e.g. sepsis). We investigated AI in cirrhosis without infection or hemodynamic instability. Methods: A total of 101 consecutive patients with cirrhosis were studied. AI was defined by a total serum cortisol (TC)\18 lg/dl at 20 or 30 min after injection of 1 lg of tetracosactrin. Transcortin, calculated free cortisol (cFC), and free cortisol index (FCI) were assessed in a subgroup of 41 patients, with FCI [12 representing normal adrenal function. Results: AI was present in 38 patients (38%). Child score (median, 10 vs 7, p \ 0.0001), MELD score (median, 17 vs 12, p \ 0.0001), ascites (68% vs 37%, p \ 0.01), basal TC (median, 7.6 vs 14.9 lg/dl, p \ 0.001), albumin (28 ± 0.8 vs 33 ± 0.7 g/L, p \ 0.0001), INR (median, 1.6 vs 1.2, p \ 0.0001), total bilirubin (median, 51 vs 31 lmol/L, p \ 0.05), total cholesterol (median, 120 vs 142, p \ 0.05), and LDL (median, 76 vs 81, p \ 0.05) were significantly different between those with and without AI. ROC curves showed a basal TC 612.8 lg/dl to be a cut-off value closely associated with AI. The cFC was significantly related to TC for baseline values (R = 0.94, p \ 0.0001), peak values (R = 0.90, p \ 0.0001), and delta values (R = 0.95, p \ 0.0001), in patients with and without AI. However, no patient had a FCI \12. Conclusions: AI defined by an abnormal response to 1 lg tetracosactrin is frequent in stable patients with cirrhosis, in the absence of infections or hemodynamic instability and is related to the severity of liver disease. However, evaluation of the true incidence of AI should comprise direct assays of free cortisol. Clinical consequences of AI need to be explored.

S295 Efficacy of rifaximin in the treatment of colonic bacterial overgrowth in ibs patients: preliminary results A. Tortora1, M. Gabrielli2, F. Purchiaroni1, V. Ojetti2, L. Sparano1, G. Vitale1, G. Gigante1, E. Scarpellini1, A. Gasbarrini1 Internal and Gastroenterology Unit; 2Emergency Department, Gemelli University Hospital, Rome, Italy

1

Introduction/Objectives: Data from our group (ScarpellIni et al. UEGW 2010) have shown a significant association between abnormal specific colonic sugar fermentation and some abdominal symptoms generation such as bloating in irritable bowel syndrome diarrheaprevalent (IBS-D) patients. Rifaximin is the gold standard for IBS-D treatment. It is still unclear if the colonic bacterial overgrowth remodulation with antibiotics may positively affect bloating in this subset of IBS pts. Aims & Methods: Aim of the present study was to assess the impact of the specific colonic hydrogen production treatment in bloating IBSD patients. IBS-D patients, according to the Rome III Criteria, with normal colonic transit time and without SIBO performed lactulose breath test (LBT) and filled a VAS questionnaire for gastrointestinal symptoms. We divided the patients into two groups according to the presence (IBS-B+) or not of bloating (IBS-B-) as prevalent symptom. Colonic H2 excretion curve (AUC) was used to evaluate the amount of H2 excreted with breath starting from 75 min to 180 min after the lactulose ingestion. The IBS-B+ group was successively randomized to oral rifaximin 1200 mg/day or metronidazole 800 mg/day per one week. Colonic H2 AUC was reassessed together with GI-symptoms during the LBT one month after the treatment. Differences among groups were evaluated with t-Student paired test, values variation with ANOVA. Correlation was calculated with Spearman not-parametric test. Results: We enrolled 87 IBS-D patients. H2 AUC was statistically different between 47 IBS-B+ and 40 IBS-B- pts (4387 ± 518 vs 2504 ± 185 ppm/min, p \ 0.05). There was a statistical correlation between bloating VAS AUC and H2 AUC values in IBS-B + but not in IBS-B- pts (R = 0.32, p = 0.005; R = 0.09, p = NS, respectively). 17 pts were randomized to rifaximin (R), 20 to metronidazole (M). No major side-effects occurred however 3 out of 20M pts referred mild headache and weakness. H2 AUC after treatment was significantly lower after both treatment groups (4196 ± 501 before and 2307 ± 197 ppm/min after R; 4057 ± 218 before and 2156 ± 207 ppm/min after M; both p \ 0.05). The AUC delta was not statistically different between R and M (1889 vs 1901 ppm, p = NS). The bloating AUC significantly decreased after both treatments (86 ± 5 before and 36 ± 4 after rifaximin and 82 ± 3 before and 32 ± 6 after metronidazole, both p \ 0.05) without significant difference among groups. Conclusion: The present study confirms an involvement of abnormal specific colonic sugar fermentation in symptom generation in IBS patients. Rifaximin seem to have the same efficacy in symptoms improvement as compared with a more gram-negative- and anaerobes-specific systemic antibiotic but without the occurrence of sideeffects. Further larger placebo-controlled studies are needed to confirm these preliminary results.

NAFLD and Mediterranean diet adherence F.M. Trovato, C. Pirri, A. Tonzuso, A. Pennisi, G.F. Martines, G. Trovato, D. Catalano Dipartimento di Medicina Interna, Sezione di Diagnostica e Terapia Medica, Universita` di Catania, Catania, Italy

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S296 NAFLD (Non-Alcoholic-Fatty Liver - Disease) because of its association with obesity, diabetes and insulin resistance (IR), can be considered the hepatic expression of metabolic syndrome. Mediterranean d Diet is a behavioral, clinical and epidemiological paradigm of healthy lifestyle. Relationship between adherence to Mediterranean diet score (AMDS) and NAFLD, a condition secondary to unhealthy eating habits, reduced physical activity and genetic factors, were studied. Methods: We studied 274 consecutive subjects (160 F, 114 M) with a mean age of 46.21 ± 12.88 years and BMI 30.33 ± 5.98, referred to our DH for nutritional counseling. Exclusion criteria were the presence of viral hepatitis, toxic or autoimmune disorders, alcohol abuse (less than 20 ml/day), diabetes, use of hepatotoxic drugs, insulin resistance. This last was evaluated as HOMA (Homeostasis Model– Assessment) and adherence to Mediterranean Diet was assessed by a validated score (AMDS: range: 0-55). Patients underwent ultrasonography of the upper abdomen and severity of steatosis was assessed by Bright Liver Score (BLS). Results: Patients were 133 NAFLD and 141 non-NAFLD; these were the control group, matched for age, sex and physical activity (Baecke Questionnaire). A lower adherence to the Mediterranean diet has been observed among patients with NAFLD compared with controls (33, 51 ± 3.82 vs. 35.62 ± 4.42; p \ 0.0001). The two groups also differ in BMI (33.31 ± 5.32 vs. 27.55 ± 5.21, P \ 0.0001) and HOMA (4.33 ± 3.85 vs. 2.03 ± 0.90, p \ 0.0001) that are higher in NAFLD subjects. There is an inverse correlation between BLS and AMDS (r = -0.175, p: 0.004). In the linear regression model, weighted by gender (AMDS lower in women), BMI (p \ 0.0001), HOMA (p: 0.0004) and AMDS (p \ 0.0001) explained 55.1% of variance BLS. The Odds ratio shows that the risk of more severe liver steatosis is increased by the greater degree of obesity (OR: 8.747, CI: 5.051 to 15.147), by higher values of CRP (OR 2.624, CI: 1.350 to 5.101) and HOMA (OR: 4.392, CI: 2.143 to 9.001), and decreased by 50% from a greater degree of adherence to a Mediterranean diet (OR: 0.575, CI: 0.354 to 0.835). Conclusion: Greater adherence to Mediterranean diet is associated with lower prevalence and severity of fatty liver. Exercise and nutritional profiles consistent with the Mediterranean diet, as in the case of the current guidelines, may improve and/or prevent this and other related conditions.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 transport in plasma by Tf. In the present study, we aimed to verify if liver dysfunction determines an alteration in metals homeostasis which could play a role in the pathogenesis of HE. Patients and Methods: Four groups of patients were enrolled in the study: normal controls without history of liver disease (CON), patients affected by noncirrhotic chronic hepatitis (CH), and patients with liver cirrhosis without (NENC) or with (ENC) anamnesis and/or ongoing clinical signs of overt HE. All patients and controls: 1) underwent venous blood drawing for determination of Cp, Cp activity, iron, and Tf; 2) were evaluated with the repeatable battery for the assessment of neuropsychological status (RBANS), in order to evaluate their cognitive status; 3) underwent 10-20 electrodes system EEG with qualitative evaluation of rhythm. Biochemical variables were measured in automation, employing validated methods (iron with a colorimetric method; ceruloplasmin and transferrin with immunoturbidimetric methods; ceruloplasmin activity applying an automation to kinetic methods). The ratios Cp activity/Cp and Cp/Tf were also calculated as recognized indices of specific Cp activity and of the Cp-Tf system functionality, respectively. Data are expressed as median values and 95% C.I. Comparisons between groups were carried out by the Mann Withney U test. A p \ 0.05 was considered statistically significant. Results: Fourteen CON, 7 CH patients, and 18 cirrhotic patients (8 NENC and 10 ENC), were studied. At RBANS, cirrhotics performed significantly worse with respect to CON and CH patients (p \ 0.01). EEG alterations suggestive of HE were observed in 3 out of the 10 ENC patients but in none of the patients from the other 3 subgroups (p \ 0.01). Aspecific EEG alterations, compatible with HE, were observed in 7 ENC with respect to only 3 patients from the other subgroups (2 NENC, 1 CH patients, 0 CON) (p \ 0.01). Biochemical variables are reported in Table 1.

CON

CH

NENC

ENC

Cp (mg/dL)

28 (23-32)

24 (22-27)++

28 (18-35)

24 (19-28)+

Cp activity (I.U./L)

102 (76-135)

85 (53-111)

117 (56-177)

52 (8-107)++,&,ı``ı

Cp activity/Cp 3,6 (3,1-4,2)

3,4 (1,9-4,6)

4,6 (2,4-5,7)

2,2 (0,4-3,9)++,&,ı``ı

Iron (lg/dL)

85 (23-162)

75 (51-161)

97 (50-359)

82 (56-265)

Tf (g/L)

2,5 (1,7-1,1)

2,8 (2,1-3,1)

3,1 (1,5-4,8)

1,7 (0,8-4,4)++,&&,ı``ı

Tf Sat (%)

28 (8-70)

23 (15-45)

20 (10-106)

66 (11-116)+

Cp/Tf

11,1 (9,2-14,7) 8,8 (7,2-11,4) 9,4 (6,2-12,1) 15,2 (6,0-7,9)+,&,ı`

* p\0.05 Vs CON; * p\0.01 Vs CON; &p\0.05 Vs CH; &p\0.01 Vs CH; * p\0.05 Vs NENC * p\0.01 Vs NENC

Severe alterations in metal homeostasis in patients with hepatic encephalopathy U. Vespasiani Gentilucci, M. Marano, G. Galati, C. Mazzarelli, C. Altamura, F. Ursini, M. Tombini, L. Quintiliani, R. Squitti, M.C. Siotto, F. Vernieri, A. Picardi Universita` campus Bio-Medico di Roma, Roma, Italy Background and Aims: Neuronal oxidative stress has been strongly implicated in the pathogenesis of hepatic encephalopathy (HE). Normal liver functioning, by producing ‘‘scavengers’’ proteins like transferrin (Tf) and ceruloplasmin (Cp), prevents metal systemic overload, which is a great contributor to oxidative damage. A normal Cp activity is required for the oxidation of ferrous iron into ferric iron, therefore preventing its tissue accumulation and permitting its

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While demonstrating nonsignificant fluctuations in CH and NENC patients, Cp activity, Tf, and the ratios Cp activity/Cp and Cp/Tf showed significant alterations in ENC cirrhotics compared with the other 3 subgroups. Moreover, also Cp and Tf Sat were altered in ENC patients with respect to CON, while no differences were observed between subgroups in iron concentrations. Conclusions: These results demonstrate the presence of strong alterations in metal homeostasis in cirrhotic patients with HE. In particular, the reduction in Cp and Cp specific activity, together with that of Tf, contribute to a reduced capacity to contrast pathological metal tissue accumulation, possibly also in the brain, leading to oxidative stress. The significant elevation in Tf Sat is consistent with this hypothesis. The increase of the Cp/Tf ratio represents the activation of an ineffective antioxidant system. Future objectives: 1) increasing the number of patients; 2) support the existence of brain metal accumulation by specific imaging analyses.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Adenomas in cirrhosis: did you know? G. Vidili, V. Pretti, M.L. Cappai, M. Masala, L. Cuccuru, G. Delitala Clinica Medica, Azienda Ospedaliero Universitaria Sassari, Italy A 78-years-old man with an history of arterial hypertension, diabetes mellitus type 2, chronic obstructive pulmonary disease and benign prostatic hypertrophy was admitted in our ward to investigate the presence of focal liver lesions detected after a conventional ultrasound. Physical examination and blood tests were unremarkable. Triphasic CT scan of the liver showed an hypertrophy of the first segment with irregular borders as in chronic liver disease associated with an area of 23 mm in diameter located in the seventh segment hyperdense in the arterial phase with rapid wash-out in the portal phase, suspected to be an hepatocellular carcinoma (HCC). A second ultrasound of the liver performed in our department detected five focal lesions, located respectively in the segments IV, V, VI and VII with size range between 20 and 43 mm in their maximum diameter. These lesions evaluated by contrast-enhanced ultrasonography (CEUS) showed hypervascular aspect during the arterial phase followed by hypovascular appearance in parenchymal phase. Given the discordance between CT and CEUS in the number of lesion detected and in the suspicion of malignant lesions, we performed an ultrasound guided liver biopsy of the bigger lesion, not previously visualized by CT. Biopsy results showed typical aspects of adenoma in the context of micro- and macronodular cirrhosis. Fecal occult blood test was highly positive and an endoscopy of the colon identified a moderately differentiated adenocarcinoma of the caecum infiltrating the lamina propria. We therefore performed a biopsy on all liver lesions with histopathologic diagnosis of hepatocellular adenomas. Subsequently, after the staging of colon cancer, was performed right hemicolectomy. Hepatic adenomas are uncommon benign epithelial liver tumors that develop in non cirrhotic liver generally in young women who have prolonged use of oral contraceptives, after treatment with androgenic steroids and glycogen storage disease type 1. We report a case of a male patient with liver cirrhosis of unknown origin in which we have characterized histologically five adenomas. Regarding our knowledge, in literature have not been reported cases of adenomas in cirrhosis and our case should be the first one. Another interesting point is that adenomas were mimicking malignant lesions, indeed both CT and CEUS described these lesions as typical for HCC, since developed in patients with liver cirrhosis. Indeed according the previous and the current AASLD guidelines non invasive diagnosis of HCC could be done, avoiding biopsy and leading to a wrong non invasive diagnosis. We think that should be taken a step back with regard to the criteria of non-invasive diagnosis of lesions identified in a cirrhotic liver, and if a lesion shows a wash-out biopsy should always be performed. Currently there is no established treatment modality for hepatic adenoma because of the limited number of cases and we have decided to follow up the focal liver lesions with an ultrasound every three months.

Gerontology and geriatric medicine Relationship of serum free thyroxine (FT4) and thyroid stimulating hormone (TSH) with insulin resistance in an aged obese euthyroid population M. Benigno*, F. Resta*, G. Barile*, V. Triggiani**, L. Marasciulo*, P. Suppressa*, E. Guastamacchia**, C. Sabba’* * Department of Geriatrics and Rare Diseases Center, University of Bari ‘‘Aldo Moro’’, Italy; ** Department of Endocrinology and Metabolic Diseases, University of Bari ‘‘Aldo Moro’’, Italy

S297 The aim of the study was to evaluate the impact of TSH and FT4 on insulin resistance in aged obese euthyroid people. We randomly selected 171 free-living subjects (98 M, 73 F), aged 65-87 years. The patients with abnormal thyroid function or diabetes and those treated with drugs affecting thyroid function were excluded. BMI, waist circumference, serum TSH and FT4, plasma glucose and insulin were measured as well as HOMA-IR (for insulin resistance), HOMA-b cell function (for insulin secretion) and QUICKI (for insulin sensitivity). The following diseases were screened: hypertension, arrythmia, coronary hearth disease, hearth failure, peripheral arteriopathy, dementia, stroke, Parkinson disease. The prevalence of comorbidity was 36,1%. After adjustment for age, sex, BMI and waist circumference, a significant inverse correlation of TSH with insulinemia (p \ 0.09), HOMA-IR (p \ 0.01) and HOMAb cell function (p \ 0.04) was demonstrated, while there was a significant direct association with QUICKI (p \ 0.01). Considering FT4, a significant positive correlation with insulinemia (p \ 0.003), HOMA-IR (p \ 0.008) and HOMA-b cell function (p \ 0.03) and a negative association with QUICKI (p \ 0.009) resulted. In contrast with data reported for younger and female subjects, in our population an increased FT4 (with the consequent less TSH release) raises insulin serum level, increasing both insulin resistance and secretion, and reducing insulin sensitivity. This could be explained by the higher age of our subjects, the prevalence of males, and by the consistent comorbidity that is a pivotal characteristic of aged people.

Takotsubo cardiomyopathy in an elderly patient with severe Alzheimer’s disease A.P. Cerri, F. Teruzzi, M. Gregorio, G. Bellelli, G. Annoni Department of Clinical Medicine and Prevention, Geriatric Clinic, University of Milan-Bicocca and San Gerardo Hospital, Monza, Italy The patient’s history presented in this case report is referred to an 80-year-old Caucasian woman with an established diagnosis of Alzheimer’s Disease (AD); in 2010 she scored 11.5/30 on the Mini Mental Status Examination (MMSE), nevertheless, with a still quite preserved autonomy (ADL 4/6; IADL 1/8). The lady had also a clinical history of arterial hypertension and hyperlipidemia and thus she was under chronic therapy with memantine 10 mg BID and chlorthalidone 25 mg. On february 2010, because of transient abdominal pain, the patient underwent abdominal US scan, that indicated a large uterine mass (15 9 11 9 8 cm), with a pattern probably ascribable to a myoma; however, she refused any further clinical evaluation and to undergo a possible surgical procedure. One year later (february 2011), in relation to the acute onset of suprapubic pain, she was taken to the emergency department (ED) of our University Hospital; physical examination revealed a distended bladder and thus Foley catheterization was performed with the drainage of 700 mL of urine. The acute urinary retention was caused by the uterine mass, as confirmed by the US scan. The bladder catheter was left indwelling and the patient discharged to home, with an appointment at the Gynecological Department, to complete the clinical assessment and define the surgical program (isteroannessiectomia and lymphadenectomy). Her daughter reported that the lady was very upset about the catheter and showed anxiety and affliction. Few hours later, the woman was admitted again to the ED with acute chest pain and shortness of breath. On physical examination, the patient was awake and disoriented; blood pressure was 145/90 mmHg and oxygen saturation of 97% on room air. The chest was clear to auscultation. Cardiac examination revealed normal heart rate, with no arrhythmia. The ECG on presentation showed sinus rhythm with ST-segment elevation of the

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S298 anterior wall of the left ventricle. Laboratory testing revealed myocardic enzymatic release (Troponin T 0.09 ng/ml; normal range: \0.01 ng/ml; MB subfraction of creatinine kinase 18.9 ng/ml; normal range: \2.88 ng/ml). With a suspicion of an acute coronary syndrome, the patient was immediately admitted to the Coronary Care Unit; she underwent coronary angiography that revealed no significant artery disease. At that time, the echocardiogram showed a normal left ventricle size with ejection fraction of 40%, akinesis of apical segment and marked hypokinesis of the mid left ventricular wall segment. A diagnosis of Takotsubo cardiomyopathy (TC) or ‘‘broken heart syndrome’’ was made. For our patient, bladder catheterization represented an important stressful event that afflicted her and appeared to be related to the development of this syndrome. She was immediately treated with aspirin, ACE inhibitor, beta-blocker and transferred to the Geriatric Clinic. The clinical course was without complications and the patient was discharged 10 days later. This case report suggests that: 1)

2) 3)

clinicians should consider TC in any patients exhibiting clinical symptoms of myocardial ischemia, especially in postmenopausal women with recent stressors; this syndrome must not be neglected in AD patients, in which emotional response may be preserved during the course of dementia; a ‘‘gentle-care’’ approach should be provided in demented patients in order to minimize their distressing symptoms; it is necessary to promote a specific attention to the clinical management of AD patients in ED, which represents per-se a stressful context.

Modifications in respiratory function after three days of polytherapy in elderly patients with chronic obstructive emphysematous bronchitis B. Curiale, V. Brucato* II U.O. Medicina Interna, ARNAS CIVICO, Palermo; *S.S. Medicina Distrettuale e Cure Intermedie- Ospedale ‘‘S. Nicolo`’’, Levanto (SP), Italy The bronchial inflammation is common in elderly people, often involving a multiorgan polypathology [1, 2]. Different studies tried to define the geriatric spirometric parameters, but they stop at 85 years old patients [3, 4, 5, 6]. In these studies, there is no reference to the residual volume (RV) related to the bronchiole-alveolar unit’s evolvement, instead of we (11) and others demonstrated [7, 8, 9, 10]. In the elderly the spirometry is not reliable and Cossi says that it leads to an underestimation of airways obstruction. The bronchioloalveolar involving in the COPD was revalued [12] emphasizing the fact that the inflammatory process of the peripheral airways (\2 mm diameter) is a determinant pathophysiologic moment in the clinical expression of COPD, modifying the V/Q ratio with following hypoxemia and ipercapnia. In mentioned study (11), in adults, the polytherapy using tobramycin 100mgx2/die im, amoxicillin + ac. clavulanic 2grx3/die iv, bromexina hydrochloride 8mgx2/die per os, betamethasone 1.5 mgx2/die iv, and salbutamol sulphate 100mcgx2/die i.m. was able to change both FEV1 and VR; therefore we have referred over-70 yrs old patients to this therapy to assess the effect on respiratory function and, because of the problems reported in the literature, we used the values of blood gas analysis (EGA). Materials and Methods: We studied 114 patients (PZ) over-70 years old arrived in the last three years from Emergency Area to our U.O. in Palermo. 60 of them were men and 54 women, mean age 81.5 ± 9.5 years, Hb 10.7 ± 0,8 g%, BMI 25,2 ± 1.2, sieric creatinine 1,1 ± 0,4 mg. 78 patients performed transthoracic B-mode

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 doppler-echocardiogram and in 62 of them (79.48%) the PAP was 33 ± 9 mmHg. The blood sample for the EGA was made using radial artery. So patients underwent to the above described polytherapy for three days, after which they repeated the EGA. We noted 3 patients with transient creatinine increase and 4 patients with transient glycemia increase. Results:

EGA parameters after 3 days of polytherapy Before

After 3 days

pO2

56,1 ± 5,2 mmHg

74,5 ± 7,3 mmHg (+28,2%)

pCO2

59,5 ± 4,1 mmHg

47 ± 2,1 mmHg (-21%)

SO2

88,2 ± 2,1%

95,9 ± 0,5%

pH

7,38

7,44

Considerations: Our data confirm that the above indicated polypharmacy is able to ‘‘unlock’’ the small airways’s commitment allowing a functional recovery of the bronchioloalveolar units and specially the alveolar ventilation restoration with a consequent re-establishment of a more appropriate ratio V/Q, increased blood pO2 and reduced blood pCO2 also in elderly people. Our data confirm previous data (11) about the role of bacterial infection in the small airways’s commitment (the association tobramycin / amoxicillin covers a very large antibacterial spectrum.) Finally, encouraged by the results obtained, we ask ourselves a question: is it possible that the patients with asthma not responsive to corticosteroids or any other uncontrolled asthma (12) have underlying bacterial infection that show the inflammation of small airways and therefore they are not ‘‘asthmatic’’ but they are affected by COPD and so should they be treated even with antibiotics? References 1. Cossi SG. Gerontology. 2007;55:3–10 2. Curiale B, Brucato V. Internal and Emergency Medicine. 2007; 2(suppl):S162 3. Pistelli R, Bellia V. Respiration 2003;70:484–489 4. Euright PL. Am Rev Respir Dis. 1993;147:125–133 5. Garcia-Rio F. Eur Respir J. 2004;24:397–405 6. Tantulli C. Respir Med. 2006;100:871–877 7. Babolini G, Girbino G. Capitolo. In: Allegra L. Patologia delle vie aeree Ed. Cortina,Verona; 1980 8. Gunella G, Gara M. L’esplorazione funzionale della respirazione Ed. Minerva Medica,Torino; 1956 9. Gunella G, Gara M. L’insufficienza respiratoria,vol III. In: Gaggi A, editor. Bologna; 1973 10. Grassi C. Il paziente con dispnea in Zanussi C. Breviario medico II Ed. Selecta Medica; 2004 11. Curiale B. Lotta Tuberc Mal Polm Soc. 1987;1/2:210–215 12. Maarten Van den Berge. Chest. 2011;139:412–423

Mini mental state examination in patients with atrial fibrillation: relationship with surrogate markers of atherosclerosis. G. De Benedetto, C. Fossati, M.A. Pappada`, C. Lo Iacono, A. Provenzano*, M. Proietti*, L. Perri*, L. Napoleone*, D. Pastori*, B. Marigliano, S. Basili* Dipartimento di Scienze Cardiovascolari, Respiratorie, Nefrologiche e Geriatriche, Sapienza Universita` di Roma; *Dipartimento di Medicina Interna e Specialita` Mediche, Sapienza Universita` di Roma, Roma, Italy

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Atrial fibrillation (AF) is the most common sustained dysrhythmia encountered in clinical practice in North America and Europe. The prevalence of this arrhythmia in the general population is closely associated with age, with values significantly higher in the elderly population. Fifteen to 30 percent of people aged 85 years and older are affected by dementia. As there is no curative treatment available, extensive efforts for the prevention of dementia in persons at risk are needed. Consistent evidence supports a possible role of AF in the development of cognitive impairment in order to include this arrhythmia among risk factors for dementia. Moreover, in old age atherosclerosis significantly contributes to cognitive impairment. To further analyze the relationship between cognitive impairment, atherosclerotic disease and AF we planned the present study. We examined 50 patients with AF aged over 65 years on oral anticoagulant treatment. Ankle brachial index (ABI) measurement, a marker of subclinical atherosclerosis considered pathologic when \0.9 or [1.3 and intima-media thickness (IMT), another established atherosclerotic marker, have been evaluated as surrogate markers of atherosclerosis. Mini Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) were performed to assess the presence of cognitive impairment, disorders of mood, difficulties in basic and instrumental activities of daily living. Nine of the 50 patients had an ABI value\0.9 (18%) and 13 of the 50 patients had an ABI value [1.3 (30%). Twenty-four of the 50 (48%) AF patients had an IMT measurement that was superior to 0.9 mm. Seventeen patients obtained a MMSE score under 24, indicating the presence of cognitive impairment worthy of more detailed diagnostic investigation. ABI\0.9 or[1.3 was significantly associated with the failure to recall test at MMSE (p=0.037) and MMSE scores inversely correlated with IMT values (r = -0.2301). This study provides evidence that, in AF patients, cognitive function, particularly short-term memory correlates with atherosclerotic state suggesting a possible strategy to improve the prevention of dementia in AF patients.

Acetylsalicylic acid (asa): protective factor in a group of patients with Alzheimer’s dementia E. Ettorre, A. Servello, E. Cerra, M.T. Vigliotta, A. Andreozzi, A. Vulcano, V. Marigliano Dipartimento di Scienze Cardiovascoli, Respiratorie, Nefrologiche e Geriatriche Universita` Sapienza Roma, Roma, Italy Alzheimer’s disease is the most common neurodegenerative disease, characterized by the presence of some neuropathological markers such as beta amyloid deposits and neurofibrillary tangles. According to the Alzheimer disease inflammatory theory there are numerous subset of inflammatory mediators that intervene in the pathogenesis of the disease. The basis for this new hypothesis is the activation of complement factors that interact with many other subsystems such as the products of complement activation (opsonins and anaphylatoxins), complement inhibitory proteins (C4BP, vitronectin and clusterin, apolipoprotein J), cytokines (IL-1, IL-6, TNF-a, TGF-b) and chemokines (IL-8, IP-10, MIP-1a, MCP-1, and neuro linfotactina actin), cyclooxygenase (COX-1 and COX-2), b2 integrins, coagulation and fibrinolysis factors (factor XII, PN-1, antithrombin III, PAI-1 and a2-MAC), acute phase proteins (C-reactive protein and a1-antichymotrypsin), apolipoprotein E, free radicals. In addition, other studies have shown that high levels of inflammatory mediators are present in the vicinity of b-amyloid deposits and neurofibrillary tangles, when

S299 neurodegeneration is not yet occurred. The main question before us today is whether the inflammatory process should be interpreted as causal factors of the damage in the AD or rather as an epiphenomenon that occurs only at a later time, and secondarily to other disease processes. With current knowledge, clinical research is not yet able to give reliable answers to these questions. The purpose of this study was to analyze the possible protective effect of antiplatelet therapy with acetylsalicylic acid (ASA) with low dose (100 mg/die) on cognitive function of a sample of patients with one risk factor for cardiovascular disease, hypertension blood, and mild cognitive impairment (MMSE [24). The study was conducted on 30 patients at the center for prospective UVA (Alzheimer Evaluation Unit), Department of Cardiovascular Sciences, Respiratory, Nephrology and Geriatric University ‘‘Sapienza’’ of Rome, subject to a first visit to T0 and then rechecked to 12 months later (T1). The sample was divided into two groups: Group ASA (acetylsalicylic acid therapy) and the non-ASA (NOT in antiplatelet therapy). The ASA group was composed of 15 patients aged C60 years, chronic treatment (at least 2 months) with ASA 100 mg / day, with anamnestic diagnosis of essential hypertension and/or patients being treated with hypotensive drugs, diagnosed with mild cognitive impairment resulting from administration of several batteries of tests (MMSE, ADL, IADL) and a neuropsychological evaluation. All patients were then subjected to a series of instrumental and laboratory examinations. The ASA group (consisting of 15 patients and with the same inclusion criteria of the ASA) has been subjected to similar investigations in the former group, the only difference is not taking ASA. The analysis of the data showed significant improvements in MMSE only ASA group patients treated with acetylsalicylic acid 100 mg/die - (p \ 0.0003). The exact evaluation of the individual test items also showed how the therapy had a positive impact on the performance of ASA group compared with controls: orientation space-time p \ 0.004, recording p \ 0.002, attention and calculation p \ 0.00006, call p \ 0.05, language, p \ 0.004. The study showed that the ASA group, 1 year later, found an increase in tests scores of MMSE, ADL, IADL compared with non-ASA. It can be concluded, based on statistical data of our study, that taking a low dose of aspirin (100 mg/day) has a protective effect against cognitive decline in patients with hypertension. In our study, aspirin was used at low dose (anti-platelet effect) but it would be interesting to examine whether with high-dose (anti-inflammatory effect) you can get the same results or better. All this opens up the debate to considerations stimulants such as acetylsalicylic acid may have a role not only protect against the onset of Alzheimer’s dementia but also in the progression of cognitive deficits.

Altered mental status in the oldest old: an unusual cause of a common problem B. Ferrari, R. Rossio, A. Maino, F. Rovelli, A.V. Marzano, A. Tedeschi, M. Cugno Ca’ Granda IRCCS Ospedale Maggiore Policlinico di Milano, Milano, Italy A 95 year-old man presented to our Emergency Department on April 2011 for declining in cognitive status; in the last two days he was febrile and was given an empiric oral antibiotic; he progressively refused eating and drinking and developed drowsiness. No other acute event was reported, in particular relatives denied head injury. The patient had a medical history of arterial hypertension, atrial fibrillation, hypothyroidism and squamous cell carcinoma of scalp, diagnosed in 1995 and previously treated with ozone therapy. His medications included amiodarone, losartan hydrochlorothiazide, levothyroxine, low molecular weight heparin.

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S300 At admission the patient was awake, confused, partially cooperative, dehydrated. His parameters were: blood pressure 130/70 mmHg, pulse rate 80 beats/minute irregular, respiratory rate 22 breaths/minute, peripheral oxygen saturation 96% while breathing ambient air, body temperature 37.2C. The neurological assessment did not reveal focal signs; rigor nucleus was absent. On physical examination a painless, necrotic and ulcerative mass with purulent secretion was evident on the vertex of the skull. Laboratory investigations showed leukocytosis (WBC 15.000/mmc) and an increase of reactive C protein (5 mg/dl, normal value \0.5 mg/dl), creatinphosphokinase (1920 U/l, normal value \174 U/l) and lactic dehydrogenases (541 U/l, normal value \480 U/l); the blood gas analysis was normal. The ECG showed atrial fibrillation with medium ventricular rate without ischemic signs. The X-ray of the chest was negative for infiltrates. In the Emergency Department the clinician decided not to perform the computed tomography (CT) of the brain, due to the lack of cooperation of the patient and absence of neurological focal signs. The dermatologist was asked to evaluate the lesion of the head, and he suggested to give intravenous antibiotics with topic medications. The patient was admitted to our Department, where he started ceftriaxone and rehydration on the suspicion of a septic origin of the neurological impairment. In the absence of clinical improvement, after sedation with promazine, the patient underwent a CT of the head which showed air bubbles within the intraparenchymal compartment; the cranial vault appeared cribriform on the vertex, at the site of the skin ulcerative neoplasia. The neurosurgeon suggested to continue the antibiotic course and asked for a CT of the cranial bone, to best evaluate the anatomical changes responsible for the pneumocephalus. In the meanwhile, the patient progressively became more lethargic; the skin cultures showed Pseudomonas aeruginosa sensitive to amikacin and piperacillin/tazobactam, which were started. The second CT of the head, performed three days later, revealed an increase of the intracranial gas, the presence of a big loss of soft-tissue and multiple discontinuities of the skull. Both the neurosurgeon and the plastic surgeon ruled out surgical options. Therefore, we continued supportive therapy until the patient became comatose and died, on the sixteenth day of hospitalization. In conclusion, pneumocephalus can be a consequence of craniofacial tumors and represents a rare cause of altered mental status.

Severe right renal cysts in patient with adult polycystic kidney disease C. Lo Iacono, D. Barra, R. De Angelis, F Falcieri, J. Escudero Ortega, M. Ringhilescu, G. Troisi, V. Marigliano Dipartimento di Scienze Cardiologiche, Respiratorie, Nefrologiche e dell’ Invecchiamento, Universita’ Sapienza Roma, Italy The patient, a 60 years old male, came to our attention after three days from the onset of fever associated with shaking chills, micro and macro haematuria and pain in right lumbar region. In 1984 diagnosis of adult polycystic kidney disease; in 1999 diagnosis of type 2 mellitus diabetes treated with oral anti-diabetic agents and in 2000 detection of chronic kidneys insufficiency (GFR 30 ml/ min). Starting from 2007 the patient has been treated with insulin therapy. Three months before admission a blunt trauma to the right renal lobe was followed the next day by pain in the lumbar region and right haematuria for which the patient was admitted to hospital. During this hospitalization severe anemia (Hb 7 g/dl, MCV 78 fl) with neutrophilic leukocytosis (12,000/mmc, Cretininemia 3.8 mg/dl) and alteration of non-specific inflammatory markers were detected. Due to a suspected rupture of a renal cysts a CT-ABDOMEN PELVIS

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 without contrast was performed. Results showed increased kidneys volume with many cysts of varying sizes, several cysts on the right side, the biggest with radius of about 6 cm with irregular septa and a dense ematic type core, and fluid imbibition of peri and para renal adipose planes. The patient underwent a transfusion of two units of blood, intravenous levofloxacin, furosemide, calcitriol 0.25 mg 1 cp, and then was sent home with the diagnosis of severe renal cysts. Seven days after discharge the patient was again hospitalized for a further onset of continuous-remittent fever (CT max 39  C) associated with shaking chills, micro- and macrohaematuria. Blood tests showed neutrophilic leukocytosis (GB 18.000/mmc) associated with hematuria, leucocyturia, proteinuria, bacteriuria. A new CT-ABDOMEN PELVIS scan was performed which confirmed the severe renal cyst on the right, compression the functional parenchyma by cysts, prostatic hypertrophy, for which it was submitted to a cystoscopy with double-J ureteral stent placement pelvis bilaterally. Due to fever and macrohematuria persistence a bilateral nephrectomy was proposed that the patient refused. Two days after discharge the patient came to us voluntarily for the suspicion of an infectious complication of the hemorrhagic cysts. Repeated blood and urine cultures were performed and, in consideration of the clinical question (nephrectomy?), a functional investigation via a URO MRI without contrast was carried on. Results showed increased kidney volume and a lack of parenchyma replaced by multiple cysts. The larger cyst localized in the equatorial right (6.5 cm in diameter) with the presence of bleeding in context and organized blood collection in the right perirenal area. The renal cysts cause compressive phenomena on calyceal groups and on renal pelvis. Urinary tracts were in the norm. Pancreatic cystadenoma, cysts at the 7th liver segment, and hypertrophic prostate responsible for the compression of the pelvic floor. The urine culture with antibiogram test gave positive results for Escherichia coli with sensitivity to meropenem. The diagnosis the was: Acute Pyelonephritis and Severe right Renal Cysts. Improvement of clinical condition and renal function (Cretininemia 3.5 mg/dl, VGF 35 ml/min) was achieved with medical therapy alone (hydration and pharmacological therapy) excluded the indication for bilateral nephrectomy. In scientific literature (Liebovitch et al. 2002, Corman et al. 2000) indication to a radical nephrectomy is given only in presence of cancer or severe perirenal abscesses. Corman JM, Penson DF, Hur K, Khuri SF, Daley J, Henderson W, Krieger JN. Comparison of complications after radical and partial nephrectomy: results from the National Veterans Administration Surgical Quality Improvement Program. Br J Urol 2000; 86(7):782-789.; Leibovitch I, Mor Y, Golomb J, Ramon J. Chylous ascites after radical nephrectomy and inferior vena cava thrombectomy. Successful conservative management with somatostatin analogue. Eur Urol 2002; 41(2):220-222.

Antiplate therapy in patients with antiphospholipid antibodies syndrome C. Lo Iacono, R. De Angelis, D. Barra, F.M. Falcieri, J. Escudero Ortega, M. Ringhilescu, B. Marigliano, C. Saccomandi, G. Troisi, V. Marigliano Dipartimento di Scienze Cardiovascolari, Respiratorie Nefrologiche e dell’Invecchiamento, Universita’ Sapienza di Roma, Roma, Italy A 65 years old patient came to our attention complaining reduction of vision, lack of concentration and anxiety-depression starting approximately three months before. The patient was diagnosed in 1996 with antibodies antiphospholipid syndrome, and in 2006 of arterial hypertension and chronic ischemic encephalopathy with multiple cerebral ischemic events. In 2007 due

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 to a lower limb arterial obliterans disease was subjected to the placement of a bilateral iliac-femoral artery stent; in 1990 a personality disorder of schizophrenic type, with frequent episodes of depression alternating with manic disorder type. The patient was treated with oral anticoagulation therapy with warfarin sodium until December 2008 when, following the onset of bleeding in the cortico-subcortical region of the left hemisphere, the therapy was changed to vitamin K and, after the acute phase, with clopidogrel and low molecular weight heparin. During this hospitalization she was subjected to routine blood tests that showed she was suffering from dyslipidemia, positive to autoantibody ANA, anti-DS-D, anticardiolipin IgG and IgM, anti beta2GPI, LAC and normal serum values of homocysteine, protein S and protein C. The indices of coagulation showed a lengthened PTT (aPTT ratio 1.86) and a normal value INR. A EEG showed moderate electrical abnormalities in both hemispheres, with a predominance of right side. A ecocolor TSA doppler showed a plate with 40% stenosis of the left internal carotid artery and right vertebral artery hypoplasia. A transcranial eco doppler showed segmental stenosis of middle cerebral artery. A visual examination showed a bilateral quadrantopsia caused by the atrophy of the cortico-subcortical bilateral occipital lobe. A multidimensional geriatric assessment highlighted a borderline state of cognitive impairment (MMSE = 25.2), moderately depressed mood (GDS 8 / 15) and a moderate limitation in activities of daily living (ADL = 3 / 6). At this point the question that came to attention was if it was appropriate to continue to treat the patient with antiplatelet therapy combined with low molecular weight heparin, given the autoimmune disease of which she was suffering and the big risk of experiencing the same arterial thrombotic vascular events. The presence of additional risk factors for thrombosis further increased the risk of a first event in patients positive for aPL. In these patients at ‘‘high risk’’ is justified the use of low-dose aspirin in addition to oral anticoagulation. Our patient, in addition to being affected by antiphospholipid antibodies syndrome, was dyslipidemic, hypertensive and a moderate smoker and these, as mentioned above, are additional risk factors for thrombotic events in vascular. Although her INR was normal she could not be subjected to oral anticoagulant therapy because the patient already had an cerebrovascular haemorrhagic stroke three years before admission. She therefore was discharged with an indication to take antiplatelet therapy with aspirin and heparin therapy with low molecular weight.

A reversible cognitive deficit in an orthogeriatric patient - a case report V.M. Magro, L. Tafaro, R. Benvenuto, A. Martocchia, I. Indiano, P. Frugoni, E. De Marinis, P. Falaschi UO Geriatria. Az. Osp. S. Andrea Facolta’ di Medicina e Psicologia Universita’ Sapienza di Roma, Roma, Italy We describe the case report of a 77 year old woman with a history of chronic schizophrenic psychosis diagnosed at the age of 30, following an acute episode of behavioral disorder and currently treated with high doses of benzodiazepines (lorazepam 1,25 mg two times a day and diazepam 6 mg in the evening) and psycholeptics (chlorpromazine 25 mg in the evening and bromperidolo 5 mg in the evening). The patient since 1995 was suffering for smoke-related chronic obstructive pulmonary disease (COPD) (20 cigarettes/day from the age of 15) and institutionalized since 1998. She arrived at the Emergency Room (ER) of our Hospital because of a referred accidental fall, at the residential facility, with right hip pain and functional impairment. Her vital signs were in the normal ranges, the physical examination showed overweight (height 173 cm, weight 85 kg, BMI 28.4), coarse facies, thickened prolab, edentulism, macroglossia, fatuous and obtuse expression, the speech with a low voice tone and

S301 poor thought content, alternation of slightly dysphoric and lethargic mood. Bouts of productive cough were present. Vesicular murmur was all over wide, with fine crackles and rhonchi bilaterally at baseline, especially on the left. The right leg was externally rotated, shortened, with aching pain, but still active and passive movements of the right foot were allowed. The ER blood tests showed a mild neutrophilic leukocytosis (white blood cells 11.78 9 103/lL, with neutrophils 84.5%), mild hyponatremia Na 132 mEq/l, elevated D-dimer 1931 ng/ml and creatine kinase 401 U/L, the remaining parameters were in the normal range. Emogasanalisis (EGA) showed a mild metabolic acidosis. The chest x-ray revealed few areas of parenchymal consolidation at the right ilum level, likely due to an inflammation process. Cardiac activity was rhythmic with no heart murmurs or added tones, the EKG showed a sinus rhythm at 73 bpm. The right femur x-ray showed a trochanteric fracture and the patient underwent trochanter fixation nail (TFN) surgery in general anaesthesia after Anti-Deep Vein Thrombosis therapy was initiated with enoxaparin 4000 IU 1 fl sc. Due to postoperative anemia, the patient was transfused with packed red blood cells during the 3 days after surgery followed by oral therapy with iron and folate. Moreover, a prophylactic antibiotic treatment for post-operative infective complications and chronic obstructive pulmonary disease exacerbation, oral rehydration, diuretic therapy, oxygen therapy were performed. The patient was then hospitalized in the Orthogeriatric Unit, where the following post-operative laboratory tests were performed for the differential diagnosis of secondary osteoporosis: thyroid hormones, vitamin D, parathyroid hormone (PTH), alkaline phosphatase, serum and urine calcium, protidogram, 24 hours urine cortisol. These tests showed: FT4 \0.5 ng/ml (0.60-1.15), FT3 = 1:44 pg/ml (2.50-3.90), TSH = 37.97 lIU/ml (0.35 to 4.00), anti-Ab –Tg = 651 IU/ml (\40), Ab anti-TPO = 1507 IU/ml (\35), according to the diagnosis of thyroiditis with severe hypothyroidism. It was also present severe hypovitaminosis D vitamin D3 \4 ng/ml with normal levels of serum calcium and a PTH level slightly increased (90 pg/ml); the remaining parameters within the normal ranges. For these reasons, the patient started hormone replacement therapy with thyroxine 50 mcg/die, slowly and gradually increased to 75 mcg/die, anti-osteoporotic therapy with alendronic acid (70 mg/week) and cholecalciferol (5600 UI/week). We also slowly reduced the psychotropic therapy: bromperidolo 2,5 mg in the evening, lorazepam 12,5 mg as needed, chlorpromazine 12,5 mg as needed. COPD related respiratory failure was treated with prescription of low flow oxygen and aerosol therapy. During hospitalization the clinical conditions of the patient improved (apyrexia, hemodynamic stability and saline diuresis, respiratory performance) as well as the vigilance and attention status, the face mimic, spontaneous speech and better understanding; still a mild anxiety and a low voice tone were present. After twenty days the patient was moved to a rehabilitation center with the following recommendations: short term blood exams (thyroid function included), thyroid Doppler ultrasound, bone densitometry, Rx thoraco-lumbar spine and chest. Finally the patient was invited to attend the geriatric outpatient clinic. Hypothyroidism is a relatively common disease among the general population, whose incidence increases with age. Typically, patients show a subclinical form, which, if unrecognized and untreated, may progress to clinical hypothyroidism with neurological and psychiatric signs like in this case. Here we show that replacing thyroid therapy was able to improve the clinical status. Furthermore, aging, psychosis and traumatic fracture may be an important bias in the differential diagnosis of this condition. Hip fracture in the elderly is a dramatic event that often highlight a frailty condition but, as in this case, may be an opportunity to identify conditions that favor their occurrence. In our case the patient’s cognitive status, compromised by use of benzodiazepines and a severe undiagnosed hypothyroidism, could probably be the cause of the fall and the hip fracture. In conclusion, geriatric assessment of hip

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S302 fracture patients is essential for the good management of elderly patients with hip fracture.

Prognosis, quality of life and way of nutrition in dementia to PEG or not to PEG? T. Meschi*, A. Nouvenne*, A. Ticinesi*, B. Prati*, N. Cerundolo*, M. Maggio**, F. Lauretani***, L. Borghi* *Department Scienze cliniche; **Dpt. Medicina Interna e Scienze Bio-Mediche, Universita` di Parma; ***UO Geriatria, AOUNIV di Parma, Italy Background: Dementia is a disease highly prevalent in the elderly population. The effects of total enteral feeding (TEF) on patients with advanced dementia are discussed. Often progressive clinical course of the disease makes it difficult to determine duration and prognosis. Aim: To evaluate in patients with dementia discharged from the hospital with or without TEN: 1) survival rate, 2) readmission rate, and 3) quality of life (QoL) perceived by the caregiver Materials and Methods: At the Department of Internal Medicine and Critical Long-term Care in University Hospital of Parma over a period of 6 months were consecutively recruited 138 patients with dementia (M 59, F 79). All patients underwent FAST scores (Functional Assessment Stages) and CDR (Clinical Dementia Ratio) and nutritional assessment. In patients unable to eat for whatever reason and with life expectancy exceeding 30 days was given TEF via PEG. After at least 12 months after discharge, survival, readmission and quality of life through telephone interview with the caregiver were assessed. Results: 31 patients received PEG and 88 maintained a natural feeding. 19 patients were excluded because they died during hospitalization. Among patients followed-up (average 18 months - 540 days). 57 patients died with a median survival of 185 ± 203 days. Among latter, 37 (Group 1) were on natural feeding and 20 (Group 2) via PEG. Mean age was higher in group 1 (85 ys vs 80 ys, p = 0.03). CDR and the mean survival were not different in group 1 and 2 (183 vs. 189 days, p = 0.92) while the FAST score was significantly worse in Group 2 (Group 1 FAST 6d vs Group 2 FAST 7b, p = 0.03). Among the 62 surviving patients 11 had PEG (group 3) and 51 were on spontaneous nutrition (group 4). CDR and FAST scores were significantly worse in group 3 (p\0.001). However, the percentage of readmission was not different in these two groups (group 3 27% vs group 4 31%). No patients in group 3 had pressure ulcers to f-up even though 2 patients had at the time of discharge. In both groups 60% of caregivers believed patients QoL good, 20% fair and 20% poor. Conclusions: In our population enteral feeding do not seem to modify survival of patients with dementia, even if patients receiving TEN show worse disease scores. There are no apparent differences in readmission rate to the hospital or in quality of life assessed by caregivers.

Depression in multiple system atrophy: a case report C. Musacchio, A. Servello, L. Kountsevitch, G. TortorelliD’Ambrosio, E. Ettorre, P. Cicconetti, V. Marigliano Dipartimento di Scienze Cardiovascolari, Respiratorie, Nefrologiche e Geriatriche, Sapienza Universita` Roma, Italy A 69-year-old woman, who was diagnosed depression treated with sulpiride, was admitted to our hospital complaining of depression, gait disturbance, urinary incontinence. Depression did not improved. The patient’s gait became increasingly unsteady, and she felt progressively more disable. The neurologic examination disclosed

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 hyperreflexia in the lower limbs, muscular rigidity in the upper limbs, tremor involving the fingers, increased muscle tone in all limbs. Patient was ataxic with mild dysarthria. On the multidimensional geriatric assessment the patient did not present cognitive impairment, with partial dependence. (Mini Mental Test Examination (MMSE): 30 / 30; activities of daily living (ADL) 6/6, instrumental activities of daily living (IADL) 4/8). Although the assessment of mood by using the Hamilton Depression Rating Scale (HDRS) showed a middle depression (HDRS: 10), the clinical examination excluded the diagnosis of depression and sulpiride was immediately discontinued. The diagnostic process continued with the autonomic assessment which showed a hypotonic bladder and orthostatic hypotension (in the recumbent position, blood pressure was 115/85 mmHg and pulse was 102/min; in the erect position, blood pressure was 85/66 mmHg). Magnetic resonance imaging (MRI) of the brain showed atrophy, especially in the left frontal lobe, in the brain stem and in the cerebellum. Therefore multiple system atrophy (MSA) was diagnosed and we initiated rehabilitation therapy together with antiparkinsonian medication with l-DOPA. After a three months follow-up period the symptoms of depression went better while autonomic failure, parkinsonism and cerebellar dysfunction subsequently improved. MSA is a variable neurodegenerative disease that includes olivopontocerebellar atrophy, striatonigral degeneration and Shy–Drager syndrome. Literature data reported mood disorders, and particularly depression, as the first manifestation of the disease. Therefore, an initial depressive symptomatology should be included in the differential diagnosis of neurological disorders, because depression could be a symptom of other diseases and not a independent clinical condition.

Malnutrition: association with disability and mortality in old population F. Resta*, G. Barile*, M. Benigno*, V. Triggiani**, M. Gaetani*, V.A. Giagulli***, E. Guastamacchia**, C. Sabba`* * Department of Geriatrics and Rare Diseases Center, University of Bari ‘‘Aldo Moro’’, Italy; ** Department of Endocrinology and Metabolic Diseases, University of Bari ‘‘Aldo Moro’’, Italy; *** Biomedical Research Association ‘‘Guglielmo Telesforo’’, Foggia, Italy The aim of our research was to assess the impact of malnutrition on disability and mortality in aged population. 489 free-living subjects, 255M and 234 F, aged 65-83 years (mean 73.7), were randomly selected. We checked a number of diseases and calculated the Charlson index (modified) for comorbidity. To assess the level of nutrition, the following items were obtained: serum albumin and prealbumin, MNA, BMI, waist circumference and triceps skinfold. The functional ability was evaluated with ADL, IADL and motor performance (MP); we considered as disabled the subjects with 0-4 ADL score. Three years after the start of the study we checked the patients who died. Through simple correlation it has been observed that prealbumin is positively associated with ADL, IADL and MP (p \ 0.002, p \ 0.005, and p \ 0.02, respectively); in logistic regression, there was a negative correlation between prealbumin and disability (RR = 0.923, p \ 0.003), independently of age, sex and Charlson index. Albumin was directly correlated with ADL, IADL and MP (p \ 0.002, p \ 0.05 and p \ 0.0005, respectively); in logistic regression a negative association was observed between albumin and disability (RR = 0.344, p \ 0.01), adjusting for the same variables. With respect to MNA a positive association was found with ADL, IADL and MP (p\0.0005 for all); the logistic regression demonstrated a negative correlation between MNA and disability (RR = 0.732, p \ 0.02). In logistic regression, we found an inverse association of mortality with prealbumin

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 (RR = 0.930, p \ 0.004), albumin (RR = 0.367, p \ 0.01), and MNA (RR = 0.566, p \ 0.01). Finally, the anthropometric indices did not correlate with both disability and mortality. Our study has shown that low values of prealbumin, albumin and MNA are associated to increased risk of disability and mortality in the elderly. These data are consistent with literature and confirm the importance of early detection of malnutrition to prevent disability and to ensure better quality of life and longer survival.

Aortic stenosis and intestinal bleeding in elderly patients G. Scala UOC Geriatria per Acuti Day Hospital Ospedale S. Eugenio ASL RMC, Roma, Italy An eightythree year old woman, relatively in good health, with mild severe aortic valve stenosis and with good hemodynamic compensation, presented cognitive deficiency since a few months, asthenia, adinamia and dyspnea from effort. The skin and the mucosas were pale, and sinusal tachichardie and declive edemas were observed. This patient was tested at our Day Hospital Geriatric Centre and showed serious anemia (Hb 6.9 g/dl), then she had a hemotransfusion of erythrocytes. The patient did not take any platelet coagulation inhibitors, corticosteroids, or other gastrointestinal irritating drugs. Blood research appeared negative in the three successive check-up. Gastroscopy showed a: ‘‘widespread polyposis, slight bulb hyperemia, normal duodenal mucosa’’. Colonoscopy showed: ‘‘presence of few diverticula in the sigma and in the descending, and the integer mucosa’’. On the basis of test results hyperchromic and sideropenic anemia by unknown causes was diagnosed, the presence of digestive apparatus pathologies (gastric polyposis, colon diverticulosis, hemorrhoids) could justify previous occult bleeding. The patient was released in rather good health showing symptomatological regression and acceptable hemoglobin values (Hb 11 g/dl) after iron therapy by intravenous injection.

S303 required new hemotransfusions. The research of occult blood was positive, while cancer markers and other laboratory tests were within normal range. A new gastroscopy showed that: ‘‘the stomach is regular with pale and hypotrophic, small sessile polypuses with regular mucosa, pre-pyloric erosions, nothing in the duodenum. The colonoscopy showed: ‘‘normal distal ileum, no significant lesions at the bottom of the right hand side of the colon, removed micropolypus in the right side of the colon, no presence of blood in colon, the rectum is normal and the anal mucosa shows no congestion’’. A three week observation showed melena requiring treatment in our day hospital, for hemotransfusion, cycles of iron therapy and new clinical investigations, which showed a hiatal hernia together with slight chronic gastritis and modest hemorrhoidal layers with no sensible pathological relevance to justify the break up of such a dramatic symptomatology. It was then decided to perform another enteroscopy with video capsule, suspecting bleeding pathology of the small intestine which showed: ‘‘Going through the pylorus after 3 and the ileocaecal valve, where the stomach is empty there is a little area of hyperemic mucosa that may suspiciously be angiodysplasia’’. Through a right transfemoral approach we proceeded with a selective catheterism of the upper mesenteric artery and an initial mesenteric angiography which showed the presence of little signs of increased vascularization in the intestinal tract in the first section of the ileum, compatible with little angiodysplagic areas. We then did a superselective catheterism of the ileal artery afferent to the intestinal tract described and afterwards, through super selective microcatheterism with 3 French catheter. Final embolization was not performed because the risk of acute necrosis of the intestinal tract, minimal embolization (tabotamp) was performed instead. After two years the patient was asymptomatic, with occasional rectal bleeding, decreasing need of hemotransfusions and iron therapy. Fig. 1. Intestinal mucosa lesion (angiography).

Table 1 Echocardiogram M-Mode Left Ventricle : SIVd 13,3 mm DdVS 50,0 mm PPd 10,1 mm - SIVs 18,3 mm DsVS 27,1 mm PPs 15,1 mm FE 77% FS 46% S% 38% - PP% 50% MVS 268 g IMVS 163 g/m2 Aorta/Left Atrium: DAO 27,6 mm AS 40,6 mm AS/A 1,47 Doppler Mitral: VpME: 1,68 m/s VpMA 1,01 m/s GpME 11,3 mmHg - GpMA 4,1 mmHg E/A 1,67 Aorta: FVIA 1,08 m VmA -3,44 m/s GmA 53,2 mmHg - VpA 4,54 m/s GpA 82,3 mmHg TAA 104 ms Overflow TRIC: VRT -2,82 m/s GRT 31,8 mmHg PsVD 41,8 mmHg - Pulmonary artery: PAP 41,8 mmHg

Even an anemic disorder can be traced in elderly people in an atypical way and it must always be thoroughly investigated. The Heyde syndrome describes the association between calcific aortic stenosis and intestinal bleeding. Conclusion: I describe the association between calcific aortic stenosis and intestinal bleeding in elderly patients (Heyde syndrome). The diagnosis is made on the basis of colonoscopy and mesenteric angiography. It is important not to underestimate this pathology due to diagnostic and therapeutic difficulties, also considering the polypathology of the elderly patient.

Left ventricle: thicknesses - minor-medium IV Septum Hypertrophy Left atrium + IAS: LA dimensions – dilated Aorta: valvular flaps – calciphyc. Mitral: mitral insufficiency moderate Tricuspid: retrograde flow - minor medium tricuspid insufficiency

Use of rivastigmina patch in vascular dementia A. Servello, E. Ettorre, A. Vulcano, A. Petrillo, C. Musacchio, F. Bechini, V. Marigliano

Mild severe aortic valve stenosis.

Dipartimento di Scienze Cardiovascolari, Respiratorie, Nefrologiche e Geriatriche Universita` Sapienza Roma, Italy

After one year the patient presented rectal bleeding with partially digested blood and once again a state of anemia (Hb 7.1 g/dl) which

Vascular dementia (VaD) is the second leading cause of dementia in elderly, after Alzheimer’s disease (AD). VaD is defined as a loss of

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S304 cognitive function resulting from ischemic, hypoperfusive, or hemorrhagic brain lesions due to cerebrovascular disease or cardiovascular pathology. Multi-infarct encephalopathy, infarcts in strategic areas, lacunae and lacunar status, Binswanger’s encephalopathy, hippocampal sclerosis, cortical granular atrophy and watershed infarcts are common lesions, associated with neurodegenerative lesions in a high percentage of VaD in old age. The diagnosis of VaD is based on the patient history, the clinical evaluation and neuroimaging. Currently, no drugs are approved for the treatment of VaD. However, because several studies have recently reported that VaD patients present cholinergic deficits, similar to those found in patients with Alzheimer disease (AD), it is believed that cholinesterase inhibitors, which are indicated for the treatment of mild to moderate AD, may also provide benefit for patients with VaD. This study aimed to determine whether rivastigmine, a second generation cholinesterase inhibitor with selectivity for the central nervous system, with capacity to inhibit both acetylcholinesterase (AChE) and butyryl-cholinesterase (BuChE), slows the rate of cognitive decline associated with VaD. Study subjects were male and female outpatients aged 65–85 years, with Mini-Mental State Examination (MMSE) scores of at least 18 and they were included in the study if a brain magnetic resonance showed ischemic changes. Patients were divided into two groups: one group was given rivastigmine patch (9.5 mg/day) and the other continued their previous therapy, except cholinesterase inhibitors. All patients were followed for 6 months, with a first evaluation at T0 and controlled six months after treatment (T1). A complete neuropsychological examination was conducted at baseline and at the last visit. Outcomes measures were mini-mental state examination (MMSE), activities of daily living (ADL), neuropsychiatry inventory (NPI), geriatric depression scale (GDS). Statistically, data proved as the cases group, in treatment with rivastigmine, showed constant values at MMSE (0.31) compared with control cases who experienced decline of their cognitive performances (p :0.0004). The same result was found in ADL scale where cases group remained surely constant (p: 0.07) in comparison with control cases that showed a decline of their practical abilities (0.007). It is remarkable to underline as Rivastigmine-treated patients had a mean improvement in GDS and NPI scales.

Inquire critically to cure syncope in the elderly F. Stella* §, M.T. Busetto*, S. Pianetti*, L. Gottardo*, A. Semplicini* § * Internal Medicine 1, Venice Hospital; § University of Padua, Italy RM, a 91 year old male, was hospitalized for sudden onset of dyspnea with right chest pain. After careful questioning the patient referred arterial hypertension and frequent falls due to uncertain walking. Examination upon admission revealed good general conditions, frequent premature heartbeats despite normal EKG. 24-hour Holter EKG revealed almost constant atrial flutter with high ventricular response (maximum: 160 bpm), several supraventricular extrasystoles, sometimes conducted with right bundle branch block shape; when sinus rhythm was registered there were sinusal pauses with maximum length of 3.16 s. Cardiogenic syncope was diagnosed and VVI pacemaker was implanted. GS, a 79 year old female, was hospitalized due to a fall with chest trauma. Clinical history revealed permanent atrial fibrillation, stenotic aortic valve and mitral prolapse. In the past three years the patient reported several falls with bone fractures, one with lumbar trauma and D12 fracture, and underwent three hospitalizations in the previous two months because of several unreported causes. Examination at admission revealed HR = 55 AR bpm, BP=110/52 mmHg when

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 lying and 99/55 mmHg while standing up 3 min later. Bradycardic arrhythmic heart sounds with 3/6 systolic bruit. 24-hours Holter EKG was unremarkable. Tilt test documented hypotensive syncope without compensatory tachycardia (type 3). These two case reports suggests some reflection concerning syncope in the elderly patient. It is quite common that old patients, refusing an unknown, feared or disabling disease, try to hide the real symptoms related to the fall. When asked about the fall, the patient may prefer to attribute the episode to a loss of balance or to a stumble. Syncope s therefore misdiagnosed. It is crucial to raise our level of suspect, to allow the correct clinical diagnosis and management.

Aortic stenosis: a case report G. Troisi, V. Formosa, C. Lo Iacono, A. Bellomo, S. Bernardini, M. Cirene, E. D’Ottavio, R. Frezza, V. Gianturco, A. Iori, B. Marigliano, V. Marigliano Dipartimento di Scienze Cardivascolari, Respiratorie, Nefrologiche e Geriatriche, ‘‘Sapienza’’ Universita` di Roma, Italy We report a case of a 83-year-old man who presented in our department with an edema and a haematoma near a chirurgic wound after an operation of embolectomy for a left brachial artery embolism, made 6 days ago. The patient was affected by ischemic cardiomyopathy treated with percutaneous coronary intervention (PCI) and with the implantation of 2 medicated stent on the anterior descendent coronary artery in 2007, moderate aortic stenosis, bilateral atherosclerosis of the extremities, hypercholesterolemia diagnosed 20 years ago, COPD (chronic obstructive lung disease), chronic kidney disease and benign prostatic hypertrophy. He took these drugs: carvedilol, atorvastatin, low molecular weight heparin and pantoprazole. Patient weight was 78 kg. Physical examination revealed a grade 2/6 systolic ejection murmur in the aortic area and nothing relevant was detected about the other body districts. Hemochrome, white cell count, electrolyte, amylase and liver function tests were all within normal limits, but urea (76,7 mg/dl) and creatinine (1,17 mg/dl) were increased, in fact estimated creatinine clearance based on Cockroft-Gault equation was 52,7 ml/min. The hemogas analysis without oxygen was nearly normal: pH 7,43, pCO2 41 mmHg, pO2 83 mmHg, HCO327,2 mmol/l, saturation O2 98%. The surgeon cleaned the chirurgic wound, that got well, and we made an Ecocolordoppler of the left brachial artery, that showed no alterations. During the hospitalization, the patient was diagnosticated with a mild cognitive impairment (Mini Mental State Examination: 23 points), so we decided for a brain nuclear magnetic resonance (NMR) with a gadolinium infusion. This exam showed some old necrotic lesions of vascular origin in left paravermian region, in right cerebellar brain and in left semioval center. While the man was in the hospital, he had an episode of paroxysmal atrial fibrillation that was treated and converted to normal sinus rhythm with the administration of intravenous amiodarone. The patient said that it was the first episode. The electrocardiograms at the moment of the hospitalization and after this episode of fibrillation was similar; it was characterized by signs of left atrial abnormality and alterations in lateral left ventricular repolarization. Our hypothesis was that the left atrium was dilated because of the aortic stenosis, so we made an echocardiography, that showed a left ventricular hypertrophy (interventricular septum thickness of 13 mm) and a global reduction in its wall movement. The ejection fraction was of 50%. There was a left atrial dilation (anterior-posterior diameter was 48 mm and superior-inferior diameter was 71 mm) and a severe aortic stenosis. The diameter of aortic bulbus was 36 mm, the maximum gradient was 41 mmHg, the mean gradient was 24 mmHg and the valve area was 0,84 cm2. The heart surgeon gave directions to a

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 possible Transcatheter Aortic Valve Implantation (TAVI) after a coronary angiography, a left ventriculography and an angiography of aortoiliac arteries. Before this exams, we followed a hydration therapy with isotonic saline, before and after the administration of contrast media for a total of 24 hours (1 ml/kg/hour), and we administered 1200 mg of acetylcysteine 12 hours before and after the procedure. The exams were done 7 days after the NMR and showed no contraindications to TAVI, but after 72 hours there was a diuresis reduction and an increase of serum creatinine (3,5 mg/dl). The patient was immediately diagnosticated with a contrast-induced nephropathy (CIN). Physical examination did not reveal anything about lungs or legs. We began a therapy with loop diuretics and after 12 hours diuresis restarted. Serum creatinine began to reduce and after 5 days it was 1,2 mg/dl, so CIN had resolution. After this event, in view of the high risk of another exposition to contrast media during TAVI and in view of the less of aortic stenosis symptoms and of his clinical condition, we decided for a conservative therapy, in according with heart surgeon and with the patient and his family. So the man was discharged with this therapy: carvedilol, amiodarone, atorvastatin, furosemide, warfarin and pantoprazole.

Idiopathic or iatrogenic pulmonary embolism: a rare case report G. Troisi, V. Gianturco, A. Bellomo, S. Bernardini, V. Formosa, A. Iori, C. Lo Iacono, B. Marigliano, V. Marigliano Policlinico Umberto I, Sapienza Universita` di Roma, Italy Case presentation: A 61 year old man with mild hypercholesterolemia and history of peptic ulcer disease was brought to the ER some hours after he had sudden onset of cough and mild dyspnea. The patient was not overweight and had no history of recent surgery or trauma to the legs. Upon arrival in ER, the initial physical examination revealed left swollen leg (with Homans’ sign) and arterial blood gas showed pH 7.45, PaCO2 41 mmHg, PaO2 63 mmHg on room air. Routine laboratory tests showed an elevation of white blood cells (10950/microL) and fibrinogen (689 mg/dl). Chest X-Ray revealed left obliterated costophrenic angle, while Lower Extremity Doppler showed medial gastrocnemic thrombosis with presence of large haematoma inside the muscle (20 mm diameter). A chest CT scan revealed intraluminal filling defects at the level of the lower lobar segmental arteries raising the possibilities of pulmonary artery thromboembolism (PE). His anticoagulation work up showed no evidence of factor V Leiden or prothrombin gene G20210A mutation, antiphospholipid antibody screening was negative, and levels of factor VIII and homocysteine were normal. To exclude the possibility of malignance, total body CT was performed, showing negative results. All causes of PE were excluded. The patient has been in therapy with berberine (BBR) for two months. He was discharged 11 days after admission, no recurrent emboli have been observed. He is to stay on sixmonth anticoagulant therapy. Discussion and Conclusions: Pulmonary embolism is a common and potentially lethal condition. Most patients who succumb to pulmonary embolism do so within the first few hours of the event. In patients who survive a pulmonary embolism, recurrent embolism and death can be prevented with early diagnosis and therapy. Unfortunately, the diagnosis is often missed because patients with pulmonary embolism present with nonspecific signs and symptoms. We presented a rare case of idiopathic embolism in a patient in therapy with berberine. This drug is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids. Berberine lowers elevated blood total cholesterol, LDL cholesterol, triglycerides and atherogenic apolipoproteins but the mechanism of action is distinct from statins. Holy et al revealed that BBR enhances TNF-a and thrombin induced endothelial TF expression via stabilization of TF mRNA. Our patient

S305 interrupted berberine therapy. After 12 months of follow up, no recurrent emboli have been observed, suggesting that this drug could be the cause of pulmonary embolism.

Depressive symptoms predict faster cognitive and functional decline in the elderly G. Viscogliosi, P. Andreozzi, I. Maria Chiriac, N. Properzi, E. Cipriani, R. De Angelis, E. Ettorre, A. Servello, B. Marigliano, V. Marigliano Dipartimento di Scienze Cardiovascolari, Respiratorie, Nefrologiche e Geriatriche. Universita` ‘‘Sapienza’’ di Roma, Italy Background: The amnestic Mild Cognitive impairment (MCI) is associated with increased risk to develop dementia. Factors that might increase the risk of progression have been variably investigated and characterized. Several studies suggest that depression can be associated with cognitive impairment and its conversion to dementia, and further neuropsychiatric conditions such as agitation, aggression and anxiety frequently occur in MCI. Cognitive decline should in part be explained by depression itself, and it has been noted that depressive symptoms may be associated with cognitive complaints that persist even after the mood improvement. Aims: The aim of this study was to investigate the association of depressive symptoms and cognitive impairment to examine whether depressive symptoms at baseline can be a predictor of faster deterioration. Materials and Methods: 79 subjects with amnestic MCI were divided into 2 groups according to the presence of depression and evaluated at baseline, 6 months and 1 year. Functional status was assessed by the Activities of Daily Life (ADL) and Instrumental Activities of Daily Life (IADL) scales. The neuropsychological status was investigated with GDS, Mini Mental State Examination (MMSE) and Neuropsychiatric Inventory (NPI). Results: The depression MCI group (M/F:15/20; age 79.4 ± 8.1 years; MMSE:24.9 ± 0.73) at baseline differed from not-depression MCI group (M/F: 16/28; age 77.7 ± 8.1 years; MMSE: 24.7 ± 0.8) only in GDS score (p \ 0.0001) and in NPI (p \ 0.005). At 6 months they differed in GDS (p \ 0.0001) and also in MMSE (p = 0.05); no differences for ADL (p = 0.09) and IADL (p = 0.34) and NPI (p = 0.146). At 1 year we founded strong differences for GDS (\0.0001), NPI (p \ 0.0001) and MMSE (p \ 0.0001) and moderate for IADL (p = 0.03). No difference was found for ADL (p = 0.169). At the NPI evaluation the most recurrent symptoms throughout the follow-up were depression, apathy and sleep disturbances. Conclusions: The importance of depression in old age should be emphasized for its deleterious effects on comorbidities prognosis and quality of life. Our study suggests that depressive symptoms could represent a clinical predictor of accelerated cognitive deterioration and impaired functional status. Further large-scale investigations are needed.

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Infective diseases

Factors affecting hospital mortality in critically ill patients with multi-drug resistant Acinetobacter baumannii R. Andini, R. Casillo, U. Malgeri, A. Senese, R. Utili, E. Durante-Mangoni Cattedra di Medicina Interna, II Universita` di Napoli, AO Monaldi, Napoli, Italy Background: Acinetobacter baumannii (Acb) is a gram-negative bacillus commonly found in the health care environment. Its ability to survive combined with its wide range of antimicrobial resistance (multi-drug resistance, MDR) makes it one of the most successful nosocomial pathogens. Indeed, Acb is emerging as a major cause of nosocomial infections worldwide. MDR Acb infections chiefly affect immunocompromised subjects, such as those with severe underlying illnesses, undergoing invasive procedures and receiving broad-spectrum antibiotics, in particular those admitted to intensive care units (ICUs). The spectrum of Acb-induced conditions includes ventilatorassociated pneumonia (VAP), blood stream infections (BSI) and complicated urinary tract and intra-abdominal infections. In this study, we aimed at analysing the effect of patient comorbidities and their severity on the hospital outcome in a large cohort of patients affected by MDR Acb infections. Patients and Methods: From October 2008 through April 2011, we observed 190 cases of MDR Acb infections admitted to the ICUs of our tertiary care hospital. All patients were treated with antibiotics under our supervision. The severity of the underlying illnesses was evaluated at baseline for each patient by means of the Simplified Acute Physiology Score (SAPS) II, a prognostic index widely used in the critical care setting. A wide range of comorbidities was also evaluated at the time of diagnosis. Each patient was followed until hospital discharge or death. Outcomes evaluated included mortality rates, relationship between severity of underlying conditions and mortality, and the number and type of comorbidities. Results: Among 202 patients studied, 90 (44,5%) died in hospital. The average survival in those dying in hospital was 23.8 days. There was a strong association between the death rate and the baseline SAPS II (28.7% vs 62.7% for a SAPS B or [40, respectively; p = 0.000). Comorbid conditions associated with a higher death rate were renal failure (69% vs 38% in those without; p = 0.001), heart failure (63% vs 39%; p = 0.0007), diabetes mellitus (63% vs 38%; p = 0.004), ischemic heart disease (59% vs 38%; p = 0.017) and chronic obstructive pulmonary disease (56% vs 39%; p = 0.035). Upon logistic regression analysis, the only variable independently associated with in hospital mortality was chronic renal failure (OR = 2.58; 95% C.I.s 1.14 to 5.83; p = 0.023). Conclusions: Our study shows that the severity of the underlying illnesses significantly affects the outcome in patients with MDR Acb infections. The death rate dramatically increased with increasing SAPS II score. Moreover, medical comorbidities, such as chronic renal failure, significantly affect the prognosis. Further studies are warranted to ascertain whether, in patients with renal failure and Acb infection, advanced therapeutic strategies, such as dialysis and hemofiltration, may affect antibiotic pharmacokinetics and drug levels at the infection site.

Fever and haemoptysis in a BPCO affected patient A. Asti, A. D’Alessandro, C. Cristiano, G. D’Alessandro, S. Nardi, G. Maresca, P. Bellis U.O.C. Medicina Interna P.O.’’S. Maria di Loreto Nuovo’’ A.S.L. NA/1, Napoli, Italy

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 A man, 73 years old, has come in our P.S. complaining continuous fever, since about 15 days, and episodes of haemoptysis. At home he had practiced therapy with third generation cephalosporin without benefit. He has referred chronic ischemic heart disease, permanent F.A. and BPCO, with a recent long-term treatment with oral corticosteroids. A chest X-ray showed a supra diaphragmatic area of thickening on the right side and the CBC showed a significant leukocytosis (32.000/mmc) with an absolute lymphocytosis (26.000/ mmc equal to 79%), so we started a therapy with piperacillin + tazobactam 4,5 g 9 2 e.v.. Nevertheless the fever persisted, so on the fifth day we added linezolid 500 mg 9 2 e.v. After 10 days chest X-ray was repeated, showing an unchanged consolidation, so we made a CT chest with m.d.c., it proved a solid lesion with irregular margins on the baseline of the right side, hilum and precarenal lymphadenopathy and, some colliquative phenomena; HIV-test and tumor markers were negative and the study of lymphocyte subpopulations was normal. The bronchoscopy didn’t detect vegetating masses; the bronchial aspirate for cytologic examination was negative but microbiological test demonstrated the growth of different colonies of Aspergillus flavus. It was, therefore, began a therapy with voriconazole 200 mg IV 9 2, which caused a rapid normalization of temperature, he was discharged after 35 days. At home he made a therapy with voriconazole 200 mg 9 2 per os for 3 months. After these 3 months the CT scan with m.d.c. and sputum culture were both negative. The Pulmonary Aspergillosis is an infection sustained by fungi of the class of Deuteromycetes, which determine very serious lung infection, ranging from aspergilloma to acute pneumonia, usually fatal. They are involved mainly immunosuppressed patients (AIDS, granulocytopenic): in the case reported in this Congress, probably the systemic abuse of steroids has been able to create in the patient the conditions for the germination of the fungus.

Vertebral spondylodiscitis in Internal Medicine: An emerging clinical problem A. Bellodi, R. Ghio, E. Arboscello, E. Balleari, I. Ponassi, C. Passalia, C. Oneto, M. Guerrini, V. Del Bono*, E. Delfino*, E. Alessandri, V. Sicbaldi Clinica di Medicina Interna 3, Ao san martino e cliniche universitarie convenzionate, *clinica di malattie infettive, Ao san martino e cliniche Universitarie Convenzionate, Genova, Italy Spondylodiscitis represent an unfrequent clinical disorder although they are reported to be the most frequent cause of haematogenous osteomyelitis in patients over age 50. Their incidence is often underestimated due to atypical clinical presentation and/or diagnostic difficulties. Here we report five cases (3 male 2 female). All of spondylodiscitis observed in our internal medicine ward in the last two years. Median age was 74 (range 56-89). All five patients had fever, low back pain, elevation of inflammatory indexes (mainly CRP and fibrinogen); one out of five had cardiac murmur, one had a clinical history previous spinal surgery, one had a pneumonia in the previous 30 days, one had history of previous pulmonary TB. In all cases the diagnosis of spondylodiscitis was made means of CT scan, later confirmed by MRI. In only one case biopsy was performed without any pathological evidence. The diagnostic workup included quantiferon test, blood culture and echocardiography (when possible trans esophageal). In only one case we had a microbiological diagnosis (blood culture positive for MRSA). In all but one cases empirical anti bacterial therapy was started with combination of amoxicillin/clavulate and levofloxacin, in the case of the MRSA infection we later substituted amoxicillin/ clavulanate with vancomicyn. The patient with history of TB was

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 treated with anti-TB treatment. Two patients had been treated for 4 months, two are currently under treatment. The patient with suspected TB had been treated for 9 months. We observed a complete clinical as well as radiological response after the end of treatment. In the two patients with undergoing therapy we observed one clinical and radiological response and one partial radiological response. We think patient over age 50 with fever and low back pain should always undergo CT scan in order to confirm or exclude the presence of spondylodiscitis. Echocardiography should be performed as well due to the frequent cohexistence of endocarditis. Biopsy should be performed in order to get a microbiological diagnosis and choose appropriate therapeutic agents, but in our experience the clinical condition of the patients did not allow such an invasive procedure. The assessment of clinical response was performed with positron emission tomography, which appears to be a very promising diagnostic procedure. Spondylodiscitis are an emergent clinical problem, probably due to more effective diagnostic techniques and increase in susceptible population. We think that randomized trials are needed to optimize diagnostic workup, treatment strategies and follow up methods.

Microbiological surveillance for multidrug-resistant bacterial infections in a single medical ward by an electronic alert system M. Biolato*, G. Marrone*, G. Delogu**, M. Montalto*, A. Gallo*, G. Capalbo***, A.L. Scanu***, A. Cambieri***, G. Fadda**, A. Grieco*, R. Landolfi* Institute of Internal Medicine*; Institute of Microbiology**; Hospital Head Unit***; Catholic University Medical School, Rome, Italy Background: The emergence of antibiotic-resistant pathogens is becoming a major threat to public health. The purpose of this study was to evaluate the utility of an electronic alert system for a better awareness of multidrug-resistant bacterial infections in an internal medicine ward in Italy. Methods: As part of hospital nosocomial infection surveillance program, electronic alerts were sent to the hospital medical director and to the ward chief whenever any of four pre-specified multidrugresistant bacteria were isolated from a culture sent to the hospital’s Central Microbiology Laboratory. We retrospectively analyzed electronic alerts regarding isolation of multidrug-resistant bacteria in patients hospitalized in the internal medicine ward during six months period. Patient charts were reviewed to characterize the patients harboring these infections. Results: A total of 290 bacterial isolates were recovered in the study population (410 patients, mean age 66.9 years, 50.9% males), including 34 isolates of multidrug-resistant Acinetobacter baumannii, 23 of multidrug-resistant Pseudomonas aeruginosa, 17 of oxacillin-resistant Staphylococcus aureus, and 6 isolates of vancomycin-resistant Enterococcus spp. These 78 multidrug-resistant isolates were recovered from 32 patients (prevalence 7.8%), mainly from urine or Foley catheter tip cultures. The patients with these infections were generally elderly and bedridden, with more comorbidities and more medical devices. 26 (81%) of the patients with multidrugresistant infections were admitted from non-health-care settings, and in 6 (18.7%) of these cases the infection was definitely community-acquired. Conclusion: the electronic alert system used appear to be a promising tool for clinicians in order to be more aware of the increasing burden of multidrug-resistant bacterial infection. Furthermore, this system helps for taking faster therapeutic decisions such as switch antibiotic therapy or straightening contact precautions.

S307 Sometimes they come back… W. Capeci, A. Gentile, G. Rinaldi, N. Tarquinio, V. Catozzo, M.S. Del Prete, A. Balloni, L1. Falsetti, G. Filippi, G. Ciotti and F. Pellegrini Dipartimento di Medicina Interna ASUR ZT7 Ancona, Osp. ‘‘S.S. Benvenuto e Rocco’’ Osimo 1Medicina Interna, Malattie ImmunoAllergiche e Res, Medicina d’Urgenza, Ospedale Torrette, Ancona, Italy We describe the clinical case of an italian, 37 year old woman. She arrived to our first aid for Fever from about two weeks, not responsive to antibiotic and antipyretic therapies and associated with diarrhea, weight loss and amenorrhea (for two months with negative BETA HCG). At the laboratory tests we found mild anemia (Hb 11.2 g/dl), increase VES (52 mm/h), PCR (5.1 mg/dl) and fibrinogen (489 mg/dl). Serology for HIV, Mycoplasma Pneumoniae, Chlamydia Pneumoniae, EBV and Widal-Wright were negative, CMV IgG were positive. Strumental exams showed: normal ECG, normal chest X-ray and normal ultrasound abdomen. Eight sets of blood cultures were performed, all positive for a Gram negative, difficult to identify. To rule out bacterial endocarditis, transthoracic and transesophageal echocardiogram were executed, that showed mild mitral regurgitation in absence of valvular vegetations. Later microbiological lab has identified the gram-negative bacilli as Brucella Melitensis. Brucellosis is a bacterial zoonotic transmitted directly or indirectly from infected animals, ruminants and domestic pigs. It’s also known as undulant fever. Although it is commonly present with acute febrile symptoms, its clinical manifestations can be highly variable, and other signs of infection may lack. So the clinical diagnosis must be supported by the results of bacteriological and serological tests1. In this case we were ‘‘lucky’’ to experience the presence of microorganism in blood-culture before serological positivization, in fact, a subsequent Widal-Wright was positive (1:400). The patient was treated according to the guidelines with rifampicin and doxycycline with prompt resolution of symptoms, negativization of inflammatory markers and good general clinical condition. Our serological investigations have been oriented by a positive history for ingestion of unpasteurized handmade cheese in the previous weeks. Although B. Melitensis is included in the diagnostic flow-chart for FUO, nowadays it is underestimated because of high microbiological control in food processing chain, which has decreased the brucellosis’ prevalence. This underlines the importance to done and redone medical history in FUO. Reference 1. Harrison’s. ‘‘Malattie infettive batteriche’’. Mc Graw Hill. 2009

Neurocisticercosis: case report M.M. Ciammaichella*, R. Maida*, C. Patrizi*, C. Maida*, G. Cerqua*, M.L. Mecca*, P. Di Micco** *ACO S. Giovanni-Addolorata-Britannico, Roma; **UOC Medicina Interna Osp. Buonconsiglio Fatebenefratelli, Napoli, Italy Introduction: It starts with intestinal infection, often asymptomatic, due to the adult form of taenia solium cestode. The cerebral localization in the larval level may cause neurocysticercosis with appearance of convulsions. Case report: We describe a case history of a 34-year-old woman with habitual syncope-like episodes in the last 6 months lasting a few

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S308 minutes. She was compelled to go to the emergency ward for the frequency of the very last episodes. Thanks to the anamnestic examination, we found out that the woman, coming from Madagascar, has been living in Italy since 8 months in order to find a job. Since she lives in Italy, she suffers from habitual syncope-like episodes. The body temperature is 36.6 C, the arterial pressure 110/70 mmHg, the cardiac frequency 74/m RS. The patient is conscious, without any focal deficits or signs of meningism. Laboratory tests: hemochrome reveals microcytemia, normal electrolytes. All the hepatic, pancreatic and renal functions are normal. Muscle and myocardial enzymes are all negative. The arterial emogas analysis is within the limits. Coagulation, electrophoretic protidogram, urine analysis with urine culture are all within the limits. Search for neoplastic markers is within the limits. Parasitological test is always negative. Search for markers of hepatitis, TORCH complex, HIV, treponema is negative. Rachicentesis is carried out, which shows clear liquor. The bacterial culture test is negative. ECG: within the limits. Chest X-rays 2p: there are no pleuroparenchymal alterations. Abdominal ultrasound: there are no alterations in endo-abdominal organs. Muscular ultrasound and subcutaneous flat tissues: there are no cystic lumps. Electroencephalogram: it reveals graphic bi-hemispheric irritating anomalies. Cranial CT without mdc: it displays some bi-hemispherical cyst formation, with prefrontal oedema in the right side. Encephalon RM: sequences have been carried out on three orthogonal levels with SE, FSE, DWI, GR and FLAIR technique taken on T2 and T1. These last ones before and after giving paramagnetic mdc ev. We notice small nodular areas in ubiquitous distribution, particularly with variable dimensions from point form to about 10 mm. The greatest one is located in the frontal right subcortical region and seems to be surrounded by vasogenic oedema. Some of these have on the inside a small eccentric formation with high signal intensity in all the sequences. We notice that after mdc there is a strengthening of cercine in most of them. Whereas others have homogenic strengthening. One of these lesions seems to have a meningeal form. Intra-cranial ANGIO RM: TOF 3D sequence is performed with VR reconstruction. Good representation of Willis polygon and main ramifications. No aneurysmatic formation. Consequently, antiparasitarial treatment is used for neuro cysticercosis with Albendazole (Zentel) 15 mg/kg/die (es. 800 mg) PO to be taken with meals for 1 month in cycle. Antiepileptic drug has to be taken with Levetiracetam (Keppra) 500 mg, 1 tablet cpx2/die in the first week, and then gradually increasing the dosage. Moreover it must be taken Prednisone 60 mg/die over 1 month in order to reduce oedema caused by the bigger lesions, to associate with H2 PO antagonists. Discussions: It is noticeable that the syncope-like episodes reported by the woman are equivalent to epilepsy as you can see from the electroencephalogram, TC and encephalon RMN images for neuro cysticercosis. Once the patient began the antiepileptic treatment, she did not suffer anymore from critical episodes. In order to prevent any frequent convulsive crisis, it is necessary to take antiepileptic treatment, to suspend in case of radiological resolution of the lesions. Conclusions: We analysed the case report of a 34-year-old woman suffering from habitual syncope-like episodes, which come from epilepsy.

Gait deficit in a young woman with respiratory failure R. Gente*, S. Avallone*, T. Migliore*, R. Roberti**, A. Ilardi ***, L.A. Ferrara* * Dipartimento di Medicina Clinica e Sperimentale, Clinica Medica, AOU Policlinico, Federico II –Napoli; ** Dipartimento di Medicina, UOC Neurologia, AORN ‘‘A:Cardarelli’’, Napoli; *** DEA, UODS Medicina Interna, AORN ‘‘ACardarelli’’, Napoli, Italy In January 2011, a 22 year old woman was admitted in the emergency room of the ‘‘A. Cardarelli’’ Hospital in Naples, for fever of recent

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 onset, dyspnea, dysphagia and difficulty in walking. She had fever (Body temperature = 38 C), tachypnea (BR = 22/m’), and there was drowse without neck stiffness. The vesicular murmur was reduced in the lung bases, the abdomen was diffusely palpable, BP= 118/80 mmHg and HR =75 b/m’. The Electrocardiogram was within normal limits, Blood Gas Analysis in room air showed SO2= 83%, pO2= 47 mmHg, pCO2= 35 mmHg. For the subsequent, sudden deterioration of consciousness with the appearance of paraparesis in the legs, we proceeded to oro-tracheal intubation and to drain thickened secretions, whose culture was found positive for Mycoplasma pneumoniae. Chest X-ray showed ‘‘left heart shifted to the left because of possible atelectasis of the lower lobe. The right lung was hyperdiaphanous as vicarious function’’. As requested by the consultant neurologist, she practiced brain CT with negative results and lumbar puncture [the spinal fluid is clear with albumin/citologyc dissociation (total protein 84 mg/dl, cells = 1/mmc) in the absence of microbial growth]. Chest CT was appreciated widespread consolidation of the inflammatory type of the left lower lobe with air bronchogram. Lingula showed areas of alveolar consolidation of bronchopneumonic origin. At the right lung: alveolar consolidation at the apex of the lower lobe. Blood chemistry: WBC = 11000/uL [neutrophils 89.6%], Gly = 186 mg/dl, Sodium = 132 mEq/l, Ferritin 329.6 ng/dl, PCR 56.8 mg/l, TAS 216 IU/ml. She started therapy with Ceftriaxone, Levofloxacin, Methylprednisolone and HLMW. After 5 days of hospitalization in intensive care, the clinical conditions improved (SO2 = 100%, FiO2 = 0.65) and the patient moved to the Emergency Medicine. She presented ideo-motor slowing, ptosis and weakness in the legs with ROT not elicited, and mild nystagmus in the horizontal plane, The vesicular murmur was reduced in the lung bases, there was fever (BT = 3 C). Samples blood culture were negative but a throat swab was positive for A/H1N1 virus. EEG detected ‘‘Brain electrical activity poorly regulated and fairly slow’’, while the ENG/EMG showed ‘‘a sensorimotor polyneuropathy with predominantly demyelinating appearance’’. The patient continued current therapy with the addition of linezolid (600 mg iv bid) and with intravenous immunoglobulin (IV Ig) for 5 days. At chest CT control improvement of the inflammatory process in the left lung where there is still an atelectasic strip in the anterior segment of the lower lobe. From the clinical point view, we observed a progressive improvement of the general and neurological conditions. The patient finally was discharged after 20 days with the diagnosis of Lobar Pneumonia in confluent and multiple foci and Miller-Fisher Syndrome (varying poliradiculonevritis of the Guillan Barre) during flu A/H1N1 virus.

Mycotic aneurysm P. Ghiringhelli, R. Cattaneo, A. Diana, S. Puricelli, T. Quirino Azienda Ospedaliera di Busto Arsizio, Dipartimento Medico P.O. Tradate, S.C. Medicina, Italy Introduction: The case described appears trivial but it shows that the Internist must have the tenacity to continue to think about the symptoms exhibited by the patient and then is able to arrive at a correct diagnosis. History: Man, caucasian 69 years, with recurring back pain for years. 5 days before admission appeared fever, epigastric pain, vomiting followed by coughing. At the same time reappeared back pain that was exacerbated by coughing. Following a sudden worsening of back pain the patient underwent a chest CT angiography that showed a diffuse atherosclerotic dilatation of the aortic arch. The pain seemed to diminish in the supine position and was interpreted by mechanical origin. In sixth day fever reappeared despite antibiotic therapy in action. A new chest CT showed the presence of a saccular aneurysm in

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 the emergence of the left subclavian artery. Endoprosthesis was placed and was continued a broad-spectrum antibiotic therapy for 30 days. Conclusions: Mycotic aneurysm, described for the first time by Sir. Wlliam Osler in 1885, were, in the age preantibiotica, a frequent complication of bacterial endocarditis, in our case probably the front door of germs was a fissured atherosclerotic plaque.

S309 Conclusion: We demonstrated a high frequency of serologic evidence of past B. henselae infection, in young Italian children, affected by various diseases, apparently free of any clinical features suggesting B. henselae infection. This observation is supported by the high circulation of Bartonella in cats.

A very dangerous fruit juice! Two cases reports of botulism Rare Candida albicans overgrowth in an immunosuppressed patient: case report of a malignant tumor-like gastric lesion P. Mansueto*, A. Carroccio**, A. D’Alcamo*, G. Ambrosiano*, A. Seidita*, F. Adragna*, A. Maria Patti*, L. Di Prima*, G. Pirrone*, I. Pepe*, S. Di Rosa***, G. Battista Rini* *Dipartimento di Medicina Clinica e delle Patologie Emergenti, Universita` di Palermo;**Ospedali Civili Riuniti di Sciacca (AG);***Azienda Ospedaliera Villa Sofia-Cervello, Palermo, Italy The gastrointestinal tract of healthy individuals is colonized by hundreds of saprophytes: mycetes, especially Candida species, are habitual ones. Under certain conditions, fungal flora may overgrowth, resulting in lesions of the digestive mucosa, which, rarely, might evolve to local diffusion and/or systemic lympho-hematogenous spreading. Mycotic infections of the stomach might, sometimes, look like benign gastric ulcers. Here we described a case of a woman, aged 64, affected by diabetes mellitus and psoriasis, in chronic treatment with immunosuppressive agents (cyclosporine), with endoscopic evidence of ulcerated vegetating gastric lesion, strongly suggestive for malignancy, due to Candida albicans infection, and completely healed after cyclosporine withdrawal and administration of oral antifungal drugs.

Bartonella henselae, a widespread, silent infectious agent: serum antibodies prevalence in Western Sicily P. Mansueto*, A. Carroccio**, A. D’Alcamo*, G. Ambrosiano*, A. Seidita*, L. Di Prima*, G. Pirrone*, I. Pepe*, G. Battista Rini*, S. Di Rosa***, E. o Cillari^, G. Vitale* *Dipartimento di Medicina Clinica e delle Patologie Emergenti, Universita` di Palermo;**Ospedali Civili Riuniti di Sciacca (AG);***Azienda Ospedaliera Villa Sofia-Cervello, Palermo;^P.O. Cervello, Azienda Ospedaliera Villa Sofia-Cervello, Palermo, Italy Background and Aims: To evaluate, in the same geographic area, the seroprevalence of B. henselae infection both in children [(observed as in- and outpatients at the ‘Children Hospital’ of Palermo (Italy)] and in healthy blood donors. Furthermore, the circulation of Bartonella in the natural reservoir (cats) was also studied. Materials and Methods: 243 children, living in Sicily (Palermo), affected by various diseases, without clinical features suggesting B. henselae infection, together with 122 healthy blood donors were serologically investigated for IgG and IgM antibodies by indirect fluorescent antibody test (IFAT). 120 stray and 62 pet cats were also analyzed only for IgG. Results: Among children 25.1% had IgG antibodies to B. henselae; 18.5% showed a titer 1:64, 2.4% 1:128, 2.4% 1:256, 0.8% 1:512, 0.4% 1:1024, and, finally, 0.4% 1:5120. Among healthy blood donors 11.4% had IgG class antibodies to B. henselae; 9.8% showed a titer 1:64, and 1.6% 1:128. All the human serum samples did not show positive results for B. henselae IgM class antibodies. 68.3% of stray cats and 35.4% of pet cats had IgG class antibodies to B. henselae.

G. A. Piccillo*, G. Liberti**, R. Restivo**, M. Gennaro***, E.G.M. Mondati****, P. Caponnetto****, R. Polosa****, G. Gasbarrini***** Department of Emergency Medicine*; Infectious Diseases Division**; Intensive Care Unit*** of Cannizzaro Hospital, Catania; ****Department of Internal Medicine, University of Catania; *****President of the Italian Association in Experimental Medicine, Italy Introduction: Botulism (from latin term botulus, ‘‘sausage’’) also known as botulinus intoxication is a rare but serious paralytic illness caused by botulinum toxin, which is produced by the bacterium Clostridium (Plectridium) botulinum under anaerobic conditions. The toxin enters the body in one of three ways: by colonization of the digestive tract (infant botulism and adult intestinal toxemia), by ingestion of toxin from foods (foodborne botulism) or by contamination of a wound by the bacterium (wound botulism). All forms lead to paralysis that typically starts with the muscles of the face and then spreads towards the limbs. In severe forms, it leads to paralysis of the breathing muscles and causes respiratory failure. Botulism can be prevented by killing the spores by cooking at 121 C for 3 min or providing conditions that prevent the spores from growing. Additional precautions for infants include not feeding them honey. The muscle weakness of botulism characteristically starts in the muscles supplied by the cranial nerves (muscles for eye movements, facial muscles and the muscles controlling chewing and swallowing) with consequent double vision, drooping of both eyelids, loss of facial expression and swallowing problems and difficulty with talking. The weakness then spreads to the arms and legs. Severe botulism leads to reduced movement of respiratory muscles with consequent dyspnea and possible respiratory failure, due to the buildup of unexhaled carbon dioxide and its resultant depressant effect on the brain with possible coma and eventually death if untreated. It can also involve the autonomic nervous system with dry mouth and throat, postural hypotension, lightheadedness and risk of blackouts, constipation. Foodborne botulism results from contaminated foodstuffs in which C. botulinum spores have been allowed to germinate in anaerobic conditions. This typically occurs in home-canned food substances and fermented uncooked dishes. It takes 3–5 days for the symptoms to become apparent and normally more than a single person can be affected simultaneously (since they consume food from the same source). Wound botulism results from the contamination of a wound with the bacteria, which then secrete the toxin into the bloodstream. This has become more common in intravenous drug users. Isolated cases of botulism have been described after inhalation by laboratory workers and after cosmetic use of inappropriate strengths of Botox. Case report: A couple of 72 year-old man and 69 year-old woman were admitted to our Emergency Department for severe asthenia, stomach ache, nausea, vomiting and xerostomia since 3 days. Three days prior to presentation, they had eaten a hand’s homemade fruit juice and became to be afflicted with asthenia, nausea and vomiting without fever. Within few hours they presented diplopia, dysphagia and ptosis followed by descending paralysis and respiratory failure. They had confused consciousness, normo-isocoric pupils, bilateral positive light reflexes. Laboratory data and gas analysis:

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S310 husband Hb: 13 g/dl, Htc: 32%, white blood cell count: 8,700 mm3, platelet: 315,000 mm3, Na: 140 mEq/dl K: 3.63 mEq/dl, Cl: 103 mEq/ dl, Ca: 8 mEq/dl; pH: 7.40, pO2: 50 mmHg, pCO2, 54 mmHg, HCO3: 32 mEq/dl, Sat O2: 84%; wife Hb: 11 g/dl, Htc: 30%, white blood cell count: 9,200 mm3, platelet: 409,000 mm3, Na: 142 mEq/dl K: 4.5 mEq/ dl, Cl: 104 mEq/dl, Ca: 9 mEq/dl pH: 7.34, pO2: 60 mmHg, pCO2, 50 mmHg, HCO3: 30 mEq/dl, Sat O2: 88%. The patients were intubated awake and ventilated by mechanic ventilator and transferred in Intensive Care Unit. According to the information taken from his parents, they had eaten fruit juice which has been made by them, 3 days before they came to the hospital. The clinical situation was thought that it might be botulism. Since laboratory tests for botulism cannot be conducted in our hospital and on the basis of our strong suspect of botulism, botulinum antitoxin (Trivalent A, B, and E) (250 mg two times) was administered as soon as possible and also piridostigmin bromure (60 mg 4 9 1), antibiotics and supportive therapy. On the 7th day of mechanical ventilation patients were extubated. The patients were transferred to neurology division as conscious and with bilateral light ptosis, well soft palate, without any paresthesia, light weakness, absent gag reflex, hypophonic voice, usual cranial nerves, absent motor lateralization signs, usual cerebellum, absent pathologic reflexes. The patients were discharged from the hospital two days later. Discussion: The diagnosis of botulism must be suspected on clinical grounds in the context of an approximate history. Conditions are often confused with botulism include Myasthenia Gravis and Guillain–Barre Syndrome. Definitive diagnosis is made by demonstration of toxin in the serum; however, the test may be negative despite of infection and cannot be conducted in all laboratories. Other fluids that may yield toxin are vomits, gastric fluid, and stool. Isolation of the organism from food is not diagnostic. In our two cases, we could not support our diagnosis with laboratory tests, but diagnosed the cases relying on the neurological examination and history of the patients. As the administration of trivalent botulism antitoxin and supportive care are essential when botulism diagnosed, the patients were transferred to the ICU where the necessary treatment is available. Clinical improvement was observed after the administration of botulism antitoxin. Our unlucky patients presented with clear signs of botulism consequent to consumption of homemade fruit juice in which it was developed unfortunately the growth of botulin toxins. This report overlights the importance to observe the correct modalities of food conservation, without which the risk to have this rare illness can become very elevated!!

Staphylococcus haemolyticus superinfection of Legionella pneumonia during infliximab therapy M. Porzio, L. Valenti, D. Bignamini, F. Ricchini, A. Palleschi*, P. Tarsia, S. Fargion U.O. Medicina Interna; * U.O. Chirurgia Toracica;  U.O. Broncopneumologia, Universita` degli Studi di Milano, Fondazione IRCCS ‘‘Ca’ Granda’’ Ospedale Policlinico, Milano, Italy We present the case of a 42-year-old man affected by psoriasis with Staphylococcus haemolyticus superinfection of Legionella pneumonia during infliximab therapy. The introduction of compounds that block TNF-a has yielded great benefits for patients affected by selected autoimmune diseases that fail to respond to classic anti-inflammatory agents, but, on the other hand, has led to an increased susceptibility to infections, in particular of those caused by intracellular pathogens, such as L. Pneumophila. Emerging evidence suggests that legionellosis can be complicated by superinfection with other agents, including saprophytic microorganisms, among which coagulase-negative staphylococci. To our knowledge, this is the first report of systemic legionellosis with superinfection by S. Haemolyticus, an emerging nosocomial multi-resistant pathogen that commonly causes

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 septicemia, osteomyelitis or endocarditis, but has not so far been associated with necrotizing pneumonia. Despite the optimal antimicrobial therapy for Staphylococcus spp. pneumonia is still controversial, evidence suggests that in patients with confirmed positivity for methicillin resistant strains, particularly if sensitivity to vancomycin is suboptimal, linezolid should be the first choice therapy, being superior to vancomycin and teicoplanin.

Another patient with abdominal pain C. Serraino*, C. Bracco*, E. Castagna*, S. Severini*, C. Brignone*, A.V. Giraudo, F. Pomero, A. Silvestri, D. Ferrigno, L.M. Fenoglio S.C. Medicina Interna, Aso S. Croce e Carle, Cuneo; * Scuola di Specializzazione in Medicina Interna, Universita` di Torino, Italy In outpatient office setting, a 66 years old man arrived to our attention for abdominal pain that was present since 1 month, but in recent exacerbation. For this symptom, he was hospitalized to the gastroenterology department, approximately 1 month earlier, and he was discharged with diagnosis of acute enteritis, adrenal incidentaloma and small left iliac aneurysm, partially thrombosed. On CT images atheromatous aorta was appreciated. At iconographic observation there was undefined periaortic sleeve. In medical history: hypertension and right nephrectomy for malignancy. On physical examination there were no major elements, except for the features of the abdominal pain, that was terebrante and led us to the clinical suspicion of aortic wall rupture. According to the clinical hypothesis, our patient was immediately hospitalized and underwent urgent abdominal tomographic study, that confirmed aortic wall rupture. The patient was immediately surgically treated with intraoperative evidence of septic rupture of the aortic wall. The patient was treated with: • • •

Aortic-left monoiliaca exclusion endoprosthesis, witch isolated renal artery in monorene patient Right-left femoral bypass Right common iliac-left kidney bypass.

The first day after surgery, there was radiological evidence of graft occlusion of the left kidney: the patient was treated with hemodialysis. During the post-operative period, pre-operative hemocultures were positive for Salmonella choleraesuis and immediately targeted systemic antibiotic therapy was started. Prevalence of microbial arteritis in adult population is 0.06–0.65%; this infectious process generally occurs on non-aneurysmal arteries. Generally, septic location is the intrarenal aorta and Staphylococco aureus and Salmonella are the bacteria most frequently involved. Atherosclerotic disease and bacteremia are etiopathogenetic factors.

Emergency Medicine Cardiac arrest without brain damages: a case report P. Astazi, M. Durante, P. Bucciarelli, S. Valentini, A.R. Pagliaroli, D. Cicchini, P. Liburdi, P. Masi, L. Sciannamea, R. Carucci. A. e De Santis Azienda Regionale Emergenza Sanitaria 118, Regione Lazio, Italy Introduction: Emergency Medicine has increased patients who can survive a cardio-circulatory arrest (CCA). However, most of them never regains consciousness and progresses to a persistent vegetative state. Case report: We managed a case of CCA in a 43-year-old female by ventricular fibrillation (VF) according to guidelines ERC 2010. This

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 woman suffered a sudden CCA caused by myocarditis during physical activity, followed by post-anoxic coma and epileptic crises. When ALS team arrived, about 8 min after, patient was unconscious, Glasgow Coma Score (GCS) was 3 and there was no respiratory effort. The ECG monitor showed a VF (Fig. 1): the first shock at 200 J was delivered. The next revaluation showed a rhythm asystole (Fig. 2). After another 2 min of CPR monitor showed again a VF, so a 2nd shock at 200 J was delivered (Fig. 3). After a further 2 min, which were seeing a gradual reduction of cyanosis and miosis, a weak carotid pulse became palpable. The rhythm was sinus, heart rate of 160 b/min, narrow complex (Fig. 4). Patient started to breathe but remained unconscious with GCS 3. An oxygen saturation of 98% was achieved with assisted ventilation and patient was transferred to the Emergency Department. During the hospital stay within the first 24 h there was a rapid recovery of cognitive functions with a GCS 15, Glasgow Outcome Scale (GOS): 5, good recovery, remaining only mnesic lacunae of the episode. Fig. 1. VF pre-shock Fig. 2. Cardiac asystole Fig. 3. VF recovery and consequent 2nd shock Fig. 4. Sinus rhythm, GCS 3, pupils reactive to light

S311 was return of spontaneous respiration soon after resuscitation, and there was pupillary response to light. Conclusions: The prediction of neurological outcomes in an unconscious survivor of CCA remains difficult. It is closely related to speed of rescuers and to high quality CPR. Pupillary response to light after ROSC seem to be a good, early and fast indicator of good recovery, according to Levy’s et al. observations. References 1. Jerry P, Nolan et al. Guidelines for resuscitation 2010 Section 1. Executive summary. Resuscitation 2010;81:1219–768 2. Levy et al. Predicting outcome from hypoxic-ischemic coma. JAMA 1985;253:1420–6

Role of anti-shock maneuver during basic life support P. Astazi, L. Sciannamea, R. Carucci. A. e De Santis. Azienda Regionale Emergenza Sanitaria 118, Regione Lazio, Italy Introduction: During sudden cardiac arrest (CCA) a progressive reduction in cardiac output is established and cardiopulmonary resuscitation (CPR) by external chest compressions may provide only a small blood flow (about 30% of normal rate) but critical to prevent heart and brain injuries. Aim of the Study: To further increase and early the cardiac output, we evaluated the effectiveness of anti-shock maneuver (ASM) during CPR in unconscious patient not traumatic. ASM consists in the fast raising and in the keeping up of the victim’s legs by another rescuer. ASM determines the blood down-flowing by gravity into the wide abdominal vases leading to an increase of amount of blood volume (about 400 cc) moreover it increases the return of blood flow to the heart and reduces the vascular compartment. Materials and Methods: We investigated 90 consecutive subjects affected by referred unconsciousness status not traumatic, to which we made to practice ASM during basic life support (BLS), as soon as another aid comes to help, by telephonic instructions, before our arrival on site. We assessed peripheral oxygen saturation by finger infrared spectrophotometer device when we arrived. Accuracy of the instrument is not specified below 70%. Patients affected by CCA were divided into 3 Groups: Group 1: without BLS performed by witnesses, Group 2: with BLS performed by witnesses, Group 3: with BLS and ASM performed by witnesses. Results: The arrival medium time was about 8 ± 3 min after EMS call. We obtained a rapid and ready recovery in all cases of syncope caused by severe hypotension (N = 36) and the stabilization in all cases of shock caused by symptomatic bradycardia (N = 14): O2saturation ranged from 92 to 98%, GCS 15. Table 1 shows O2-saturation in CCA patients: a better but not enough O2-saturation in Group 2 as respect to Group 1. A higher O2-saturation was achieved in Group 3 as respect to Group 2 in the subgroup with VF (O2-Sat 68% versus 53%).

Discussion: The post-anoxic brain injury is very serious. The outcome’s prediction of neurological recovery in an unconscious survivor of CCA is mainly based on clinical data. This patient had no history of epilepsy, and it would therefore be reasonable to attribute the cause of the subsequent epileptic crisis to hypoxic cerebral damages. These symptoms are considered an indicator of severe impairment of brain function. We ascribe the rapid brain’s improvement instead observed in our case, to the strength of ‘‘chain of survival’’, that are the actions linking a victim of CCA with survival, and to the high quality CPR performed by advanced life support (ALS) team of the A.R.E.S. 118–REGIONE LAZIO. In our case there

Table 1 Group 1: without BLS. Group 2: with BLS. Group 3: with BLS and ASM Rhythm sex n Age VF

O2Sat.

n Age

O2- n Age Sat.

O2Sat.

M

2 72 ± 3 \51% 5 70 ± 3 54% 2 68 ± 2 68%

F

2 77 ± 2 \51% 6 73 ± 2 53% 2 76 ± 3 69%

Asystole M F

6 69 ± 2 \51% 2 69 ± 2 53% 2 74 ± 2 55% 7 79 ± 2 \51% 2 74 ± 1 52% 2 75 ± 2 53%

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S312 Discussion: The accuracy of the measurement of oxygen saturation during CCA is affected by vasoconstriction. However early and highquality BLS plus ASM improves oxygen saturation and seems rise number of patients with VF when EMS team arrives. The good effect on cardiac output of ASM is immediate and consequently coronary perfusion may improve generally reducing the myocardial ischemic hypoxia and particularly of myocardial specific tissue. Furthermore the Starling’s heart law’s activation reduces cardiac batmotropism supporting the restart of a new sinus rhythm and leading to a positive increase of the cardiac inotropism. These rapid hemodynamic changes may protect cerebral tissue from ischemic anoxia and may aid to a complete neurological recovery in the case of CPR’s success. ASM through these hemodynamic mechanisms may be particularly useful in cases of PEA. Conclusions: These findings obtained on a limited and preliminary cases review, confirm the positive effect of ASM during syncope and bradycardia both on hemodynamic aspects and on full cerebral function recovery. In the victims of CCA without BLS were found especially asystole rhythm, while those with BLS were most still in VF. In the few cases in which BLS and ASM were executed the better O2-saturation observed seems reinforce the ‘‘chain of survival’’. Although the maximum effect of ASM is transitory, further examinations are needed to validate ASM’s role during CCA.

Sturge-Weber syndrome: analysis of eight patients with epilepsy L. Carini, E. Caroli, G. Trillo`, E. Cantarano, M. Cimatti, A. Raco Policlinico S. Andrea, Facolta` di Medicina e Psicologia Neurochirurgia, Roma, Italy Sturge–Weber syndrome is a sporadic, congenital, frequently progressive disease, often associated with epilepsy. The choice of treatment of epilepsy in patients affected by Sturge–Weber syndrome is a matter of debate. Some authors suggest surgery only in patients with seizures refractory to the medical therapy, while other authors propose early surgery. We report our experience with eight patients affected by Sturge–Weber syndrome. Seven patients underwent surgery. At mean follow-up of 9.5 years three patients were seizures free, and the remainder four patients had decreasing of seizures frequency (more than 50%) and antiepileptic drug dosage. Patient without surgery showed a deterioration of his cognitive status and an increasing of seizures frequency. From this small group of patients, we have observed that seizures intensity and cognitive level before surgery result strictly related, and cognitive status remains stable after surgery. These observations suggest an early surgical treatment in children affected by Sturge–Weber syndrome with epilepsy refractory to medical therapy.

Pearson test and ‘‘CAPNO-TEC’’ study: correlative analysis of continuous variables in 20 patients with chronic venous thromboembolism. five-year experience (2006–2010) M.M. Ciammaichella, R. Maida, C. Patrizi, C. Maida, G. Cerqua, M.L. Mecca ACO S. Giovanni-Addolorata-Britannico, Roma, Italy Introduction: ‘‘CAPNO-TEC’’ study, acrostic from ‘‘chronic venous CAPNO-Thromboembolism’’ reports 20 patients, from 48 and

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 88 years old, affected with chronic venous thromboembolism (central pulmonary embolism) admitted to the unit ‘‘Degenza Breve/Sub Intensiva C’’ in the Department of Internal Medicine from January 2006 to December 2010. We calculated the following chronic criteria: (1) all the patients showed pulmonary embolism [12 months proved by angio TC; (2) all the patients suffered from post-thromboembolic pulmonary hypertension proved by echocardiogram; (3) all the patients suffered from chronic venous occlusion with particular evidence of nearest recanalization that was already reported in the previous embolic episode; (4) all the patients had pCO2 values at the entry [35 mmHg. We measured pCO82 in all the patients at the entry (FiO2 21%) with arterial sample. Their results are reported in Table 1. As a consequence, we created a database with Microsoft Access called ‘‘CAPNO-TEC’’. This database included the following fields: (1) number of patient, (2) pCO2 values at the entry with FiO2 21%, (3) chronic clinical aspects. A comparative analysis was carried out for nominal variables with the Cochran’s Q test. The aim was to check if there is a significant relationship between pCO2 values at the entry and the chronic embolism (see Table 1). Purpose of the experiment: Our research has two main goals: first of all, to check any differences in pCO2 values at the entry in 20 patients affected with chronic pulmonary embolism. Moreover, to check its statistical importance by applying the Cochran’s Q test in order to determine if the differences are due to chance. Methodology: In order to apply the Cochran’s Q test, we created Table 1. This includes pCO2 values at the entry with FiO2 21% in those patients enlisted in this case, with distinguishing values [35 mmHg, values between 35 and 45 mmHg and values [46 mmHg. To calculate v2 we apply the following formula: v2 = (k-1)[(k x)-y2]/(k y)-z=28.9. ‘‘K’’ refers to 3 variables, ‘‘X’’ refers to the total sum of squares of the 3 variables. ‘‘Y’’ stands for the total of the chosen scores. ‘‘Y2’’ is the square of the total chosen scores. ‘‘Z’’ means the sum of the squares of the chosen scores. The v2 relative value (VR) is 28.9 with degree of freedom (GL) =2. The v2 critical value (VC) per p = 0.001 is 13.816. Results: By applying the Cochran’s Q test to the pCO2 values in 20 patients, the results demonstrate how pCO2 values with FiO2 21% at the entry in those patients affected with chronic pulmonary embolism are not at all due to chance. They have indeed a significant importance because the v2 obtained relative value (VR) is 20.95 with degrees of freedom (GL) = 2, and the v2 critical value (VC) per p = 0.001 is 13.816. The differences in choice are consequently strongly significant with p \ 0,001. Discussion: The results show how comparing pCO2 values with FiO2 21% at the entry between 36 and 45 mmHg in patients with chronic pulmonary embolism is much more common than pCO2 pathognomic values \35 mmHg due to central acute pulmonary embolism. As a matter of fact, the direct consequences of the acute pulmonary embolism are: the increase in death area, bronchoconstriction connected with platelets and mastocytes, flow redistribution in the healthy alveolar capillary unit, relaxation of the alveolar capillary unit with the excitation of J receptors, tachypnea, hyperventilation, hypocapnia. In the chronic embolism, the opening of vascular shunts is vital, with flow deflection from pulmonary area to the systemic circulation, jumping over the alveolar capillary exchange. Conclusions: ‘‘CAPNO-TEC’’ study points out the correlation between pCO2 values in the arterial emogas analysis from 36 to 45 mmHg and the chronicization of illness due to the opening of vascular shunts in 20 patients with venous thromboembolism. This correlation represents a significant concordance.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392

S313

Table 1 Cochran Q test Valori pCO2 in mmHg all’ingresso FiO2 21% Soggetti

\35 36-45 [46

Y

Y2

1

x

1

1

2

x

1

1

3

x

1

1

4

x

1

1

5

x

1

1

6 7

x x

1 1

1 1

8

x

1

1

9

x

1

1

10

x

1

1

11

x

1

1

12

x

1

1

13

x

1

1

14

x

1

1

15

x

1

1

16

x

1

1

17

x

1

1

18

x

1

1

19

x

1

1

20

x

1

1

Totali Totali2

X\35=1 X36-45=18 X[45=1

Y=20

2

2

2

X\35 =1 X36-45 =324 X[45 =1

Z=20

2

Y =400

by applying parametric Pearson test in order to determine if the relationships of the variables are due to chance. Methodology: In order to apply Pearson test, we created a spreadsheet. The Pearson parametric correlation test links the independent Variable A (PEI at the entry) with dependent Variable E (Miller Score at the entry). To calculate this test we apply the formula of ‘‘r’’ coefficient (standing for the strength of the association). This is to ¯ ) (E- E¯)/ determine the Pearson product-moment correlation: R(A- A ¯ )2 R (E- E¯)2. The ‘‘r’’ value resulting from degree of H R(A- A freedom (GL) = 29 is 0.01. As the Critical Value (VC) of ‘‘r’’ \0.652 with GL=29 per p = 0.001, the Relative Value (VR) of ‘‘r’’ is 0.01: this shows a positive correlation of the covariation between the values of the two variables (A and E), which is strongly significant with p \ 0,001. Results: The Pearson test regarding 30 patients shows a strongly significant correlation (p \ 0,001) between the two variables (PEI values at the entry and Miller Score values at the entry). Therefore it is not due to chance. The obtained ‘‘r’’ value is 0,01 and ‘‘r’’ VC (critical value) per p = 0,001 is \0,652 with GL=29. Discussion: The results show how the increase in PEI value at the entry in those 30 patients enlisted in ‘‘PEI-MILLERS’’ study is connected with the increase in Miller Score pre-lysis values in all the patients at the entry (see Tables 5 and 6). Consequently, the seriousness of the tomographic picture evaluated by PEI, is directly connected with Miller Score, which is obtained from the angiographic examination. Conclusions: ‘‘PEI-MILLERS’’ study indicates how there is a correlation between the two variables PEI and MILLER SCORE in 30 patients with venous thromboembolism. This connection presents a perfect positive correlation according to the ‘‘r’’ Pearson coefficient. This means it has a strongly correspondence between the increase in PEI values and the increase in Miller Score value in 30 patients affected with central pulmonary embolism. This PEIMILLERS report presents data that complete those provided from Qanadli, Nordenholz, Nural, Ghanima, Choi, Pech, Aujesky, Miller studies.

Pearson test and ‘‘PEI-MILLERS’’ study: correlative analysis of continuous variables in 30 patients with venous thromboembolism. triennial experience (2008–2010)

Ultrasound artifacts in pleuropulmonary diseases: a useful diagnostic tool or errors in image? a multicenter study in patients with acute dyspnea

M.M. Ciammaichella, R. Maida, C. Patrizi, C. Maida, G. Cerqua, M.L. Mecca

C. Cipriani, V. Carnevale, A. Greco, G. Sperandeo, M. Piattelli, M. Villella, F. Terracciano, M. Maggi, I. De Sio V., Ostilio Palmieri, M. Sperandeo

ACO S. Giovanni-Addolorata-Britannico, Roma, Italy Introduction: ‘‘PEI-MILLERS’’ study, acrostic from ‘‘PULMONARY EMBOLISM INDEX and MILLER SCORE’’ reports 30 patients from 48 and 82 years old, affected by venous thromboembolism (central pulmonary embolism) admitted to the unit ‘‘Degenza Breve/Sub Intensiva C’’, in the Department of Internal Medicine during the triennium January 2008–December 2010. We calculated PEI and Miller Score in all patients. The result is a database called ‘‘PEI-MILLERS’’ with the following fields: (1) number of patient, (2) PEI score at the entry, (3) pre-lysis Miller Score, (4) post-lysis Miller Score. In order to check if there is a significant relationship between PEI values at the entry (independent Variable A) and Miller Score values at the entry (dependent Variable E), we carried out a correlative analysis for continuous variables with parametric Pearson test. Purpose of the experiment: ‘‘PEI-MILLERS’’ study has two aims: first of all, to check any relationships between PEI values at the entry and Miller Score pre-lysis values at the entry (T0) in 30 patients enlisted in ‘‘PEI-MILLERS’’ study during the triennium January 2008–December 2010. Secondly, to check its statistical importance

Universita` di Roma ‘‘Sapienza’’, IRCCS ‘‘Casa Sollievo della Sofferenza’’, S. Giovanni Rotondo, IRCCS Miulli, Acquaviva delle Fonti, Ospedale S. Camillo de Lellis, Seconda Universita` di Napoli, Policlinico di Bari, Italy Objective: To evaluate whether there is a difference in the number of ultrasound artifacts between normal and diseased lung in patients with acute dyspnea. Methods: We evaluated 193 patients with acute dyspnea (111 male and 82 female aged 31 to 87 years, mean age 59.4 ± 9.7 SD years) and 193 healthy subjects (105 male and 87 female, aged 19–58, mean age 46 ± 1). A transthoracic ultrasound examination was performed in all the subjects with both a convex and a linear probe. The number and type of artifacts detected at each intercostal space were evaluated. Results: There was a statistically significant difference between the number of artifacts in the group of patients and those in the control group with both the linear (mean values 2.33 ± 0.007 SE vs 2.034 ± 0.007, respectively, p \ 0.0001) and the convex probe

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S314 (2.38 ± 0.003 vs 1.90 ± 0.005, p \ 0.001). We found a significant difference between different types of artifacts between the two groups with both the probes (p \ 0.05). No significant difference in the number of artifacts between different groups of patients divided according to the final diagnosis was found (p = NS). Conclusions: Different types of artifacts cannot be considered as specific and diagnostic for any distinct pleuropulmonary disease. Hence, chest ultrasound represents a valuable but complementary technique for the study of pleuropulmonary diseases.

Aortic-caval fistula as an unusual complication of chronic periaortitis: a case report F. De Stefano, M.R. Barbella, R. Nappo, M. Saturnino, G. Gallotta Dipartimento di Medicina Clinica e Sperimentale, Universita` degli Studi di Napoli ‘‘Federico II’’, Napoli, Italy A 58-years old man presented to our structure with swollen and painful legs. He referred this sign presented in 12 h. He was an actively smoker, with no other CV risk factors: in the past he received histological diagnosis of retroperitoneal fibrosis and underwent several surgery interventions because of obliteration of the right and left ureter (the latter led to hydronefrosis of the left kidney), and for resolving adherences of the fibrous tissue. He was addressed to our structure from an Emergency Department (ED) of the territory, where he was studied with a CT that showed an abdominal aorta aneurism and an important reduction of the inferior vena cava caliber. On physical examination, the lower limbs appeared swollen, eritematous and painful, the patient had to lift them in Trendelemburg position to mitigate the pain. Deambulation was impossible. Neither masses nor murmurs were appreciated during abdomen examination. Laboratory tests showed anaemia (Hb 9.1 g/dL) secondary to chronic renal failure and increase of inflammatory markers, such as CRP, erythrocytes sedimentation rate, beta2 microglobulin and fibrinogen. Our diagnostic hypothesis: acute rupture of the aneurism, compression of inferior vena cava or opening of communications between aorta and inferior vena cava. A different CT study was needed, using multidetector technique and contrast enhancement. The images showed: in the retroperitoneum, soft fibrotic tissue developing from the renal veins outlet to the iliac veins, wrapping vascular structures. At this level, the inferior vena cava appeared with restricted caliber, with important distal swelling. This vessel and the iliac veins were early enhanced by the contrast, for the presence of an aortic-caval fistula. In the same area, the abdominal aorta appeared with regular diameter, wrapped in the fibrotic tissue (diam. 5.6 cm). No abdominal aortic aneurism was seen, but, eventually, the CT study in the ED confused the fibrous tissue with the aortic adventitia. Abdominal aorta appeared with thinning of the adventitia, demonstrating the presence of an inflammatory aneurism (non atherosclerotic). Collateral circuli were present. Thrombi were seen in the lumen of right, left external iliac vein and in femoral veins (complete obstruction of left femoral vein). Pieloureteral stent was seen on the right ureter. The left kidney was not opacified at 3 min after contrast injection. In conclusion, the patient presented a retroperitoneal fibrosis’ particular expression: chronic periaortitis, which is composed by: abdominal aorta inflammatory aneurism with a peri-aneurismatic fibrous reaction that strictly involves aorta and inferior vena cava. Thus, the therapeutic choices in this case were restricted: in fact only the closing of the fistula could resolve the clinical symptoms in our patient.

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Pharmacological therapy included antibiotic therapy, for a urinary culture positivity, low molecular weight heparin because of the patient’s immobilization, and use of amlodipine. In this case, in fact, we used this diidropiridine to induce peripheral vasodilation, and lowering systolic blood pressure, preventing the rupture of the fragile fistula wall. The closing of the fistula needed an invasive approach and an angiography was performed. A first attempt was made using a vascular plug (22 mm diameter), but an abdomen ecodoppler and a CT confirmed the persisting patency of the fistula. Then, it was necessary to use an endovascular prothesis, that was in fact positioned in the abdominal aortic lumen. After the intervention, the patient’s lower limbs swelling reduced, and pain was resolved. The patient underwent pharmacological therapy with immunosuppressing agents, steroids and azathioprine, with the aim of reducing inflammatory response. In fact, inflammation causes inappropriate fibrous tissue production as well as the continuous remodeling of the abdominal aorta adventitia, which led to the opening of a small communication tract with the inferior vena cava.

Whirlpool sign of testis, a sonographic sign of incomplete torsion F. Esposito, P. Sgambati*, M. Di Serafino*, D. Noviello, G. Vallone*, P. Oresta Struttura Complessa di Radiologia Azienda Ospedaliera Pediatrica ‘‘Santobono-Pausilipon’’ Napoli; *DAS Diagnostica per immagini e radioterapia Universita` ‘‘Federico II’’ Napoli, Italy Four children (ages 3–6 years old), came to our attention for acute scrotal pain with slight hyperemia of the scrotal skin and pain in the lower quadrants of the abdomen; only one patient, with symptoms arose more than 6 hours, had nausea and vomiting. The main causes of acute scrotal pain considered were: torsion of the testicular appendages, testicular torsion and epidydimitis-orchitis. Gray scale and color Doppler sonography of the scrotum was immediatly performed, with a 12 to 15 MHz transducer (Aloka, USA, Wallingford, CT). There were no laboratory tests available at the time of investigation. Longitudinal and transverse ultrasound scans were performed of the testis, epididymis and spermatic cord (from inguinal region to scrotum). All studies included comparative scans of the controlateral side, using the same gray scale and Doppler parameters for both testis. In all patients the testis appeared symmetrical in volume; only the patient with symptoms for more than 6 hours, showed hydrocele, testicle with more spherical morphology and diffusely heterogeneous echogenicity. All patients showed the presence of vascular signal championships with at least three poles of testis. The study included evaluation of the spermatic cord, which was estimated on longitudinal and transverse scans from the inguinal region up to the testis. The exploration of the cord throughout its course showed a spiral pattern to form the so called ‘‘whirlpool sign’’. This sign was the diagnosis of incomplete testicular torsion (\360) and it was confirmed surgically in all four cases.

How often have we said: if I had thought of it before? E. Greco, R. Villani, C. Pomara, E. Altomare, G. Serviddio Clinica Medica DIMED Universita` di Foggia, Italy A 32-year-old man referred to the local Emergency Department for vomiting, diarrhoea, abdominal pain and malaise. On presentation, he

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 appeared moderately dehydrated with normal vital signs. The abdomen was distended with tenderness in the right upper quadrant. He reported splenectomy for a car accident some years before. The history was otherwise negative. The patient was restless and febrile (temperature 39,2 C), with hypotension (arterial blood pressure 60/40 mmHg) and tachypnea. A chest radiograph was notable for right basal pulmonary infiltrate. Initial laboratory studies revealed WBC count 2,300 cells/lL and platelet count 66,000 cells/lL. Arterial blood gas analysis showed pH 7.15, pCO2 28.3 mmHg, pO2 81.1 mmHg and HCO3- 9.7 mmol/L. The patient was treated with fluid resuscitation and hydrocortisone 1 g ev. However, the patient conditions rapidly worsened, he became hypotensive and unresponsive to fluid therapy and developed a severe acidemia. A new arterial blood gas test showed pH of 6.48, pCO2 of 50 mmHg, pO2 of 78.8 mmHg, and HCO3- of 8.3 mmol/L. Laboratory studies revealed an elevation of both fibrin degradation products and D-dimers; creatinine level was 2,8 mg/dl, with a normal BUN. Total bilirubin level was 3,33 mg/dl, with prothrombin time, partial thromboplastin time and fibrinogen not detectable. The patient was intubated and started on bilevel mechanical ventilatory support. A new chest radiograph demonstrated bilateral pulmonary infiltrates. Acute respiratory distress syndrome (ARDS) and anuric renal failure quickly ensued. Large-volume of crystalloid infusion and vasopressor support with dopamine and vasopressin were started to maintain end-organ perfusion. Despite intensive treatment, a severe sepsis with multiorgan failure (MOF) developed within few hours, and the patient died within 6 h after. The patient had not received vaccination for any strain of streptococcus. Post-mortem examination revealed bilateral adrenal apoplexy in patient with lobar pneumonia and and acute congestion of the other organs. Blood cultures resulted positive for Streptococcus pneumoniae. Accordingly, primitive adrenal failure (Waterhouse Friderichsen Syndrome) due to fulminating pneumococcal sepsis in a young man with acquired asplenia was identified as the cause of death. Immune defects such as functional or anatomic asplenia can confer a predisposition to invasive bacterial infection. The association between Pneumococcal septicaemia and DIC in patients with asplenia or abnormal splenic function is well described, with post-mortem evidence of bilateral adrenal apoplexy being reported in some patients. Nevertheless, a few case reports have describes patients with normal spleens developing WFS caused by pneumococcus. The diagnosis of adrenal insufficiency resulting from adrenal haemorrhage is often overlooked of the nonspecific nature of the clinical presentation. Thus, a high index of clinical suspicion must be maintained for patients with risk factors and early diagnosis and corticosteroid treatment are essential in order to alter the poor prognosis of these patients. Several methods have been shown to be effective in preventing postsplenectomy sepsis (PSS) in asplenic patients. Such methods include patient education, prophylactic antibiotics and vaccination against encapsulated bacteria, although no features can be suggested to identify those at risk of this rare, yet devastating disease.

Clinical pathways: observation units for syncope E. Pennacchio, M. Carbone, P. Delmonaco, M.G. D’adamo, M. Autilio Pronto soccorso, accettazione e medicina d’urgenza, A.O.R. ‘‘San Carlo’’ Potenza, Italy Introduction: Syncope is a frequent cause of emergency department (ED) visit. Sometimes, a great effort is needed to make an accurate diagnosis. The presence of an observation unit (OU) allows to perform a further evaluation of the patients with diagnosis of indeterminate syncope after ED visit.

S315 Aim of the study: evaluate the differences in the admission rate and diagnosis of syncope in patients by comparing the data from 2003 (from 1 January to 30 June; OU unavailable) and 2010 (from 1 January to 30 June; OU available since 2006). Design: Before-after study. Setting Emergency Department of a community-based, 700-bed hospital. Patients and Methods: the data of 2003 were extracted from the ED manual report. The data of 2010 were extracted from the AIRO (Area Informativa Ricoveri Ospedalieri) hospital software. In 2003: 25149 visits; syncope 681 (2.7%; M/F 316/365). In 2010: 20229 visits; syncope 398 (1.97%; M/F 211/187). Were admitted to the OU the patients with indeterminate syncope and one or more of the following: cardiac disease, age [45 years, secondary trauma, abnormal ECG findings, orthostatic hypotension. All the patients had continuous ECG monitoring and routine blood tests. In patients with age [65 years, the carotid sinus compression was performed. Further tests (head CT scan, myocardial necrosis markers, echocardiography, EEG) were performed in selected patients. Results: In 2003 389/681 patients were admitted to the hospital wards (57.1%). In 2010 135/398 patients were admitted to the hospital wards (33.9%). The difference was statistically significant (X2 = 53.21; p \ 0,00001). In 2003 the following diagnosis were made: neurally mediated syncope 275 (40.3%); cardiogenic syncope 115 (16.8%); neurological syncope 30 (4.4%); orthostatic syncope 65 (9.5%); indeterminate syncope 196 (29%). In 2010 the following diagnosis were made: neurally mediated syncope 200 (50.2%); cardiogenic syncope 48 (12%); neurological syncope 23 (5.7%); orthostatic syncope 80 (20.1%); indeterminate syncope 29 (7.2%); non-syncopal transient loss of consciousness 18 (4.5%). The difference between 2003 and 2010 of the patients with diagnosis of indeterminate syncope was statistically significant (X2 = 66.53; p \ 0,00001). Conclusions: Admitting selected patients with syncope to an OU with ECG monitoring allows to reduce the number of admitted patients to hospital wards (by diminishing the number of patients with the diagnosis of indeterminate syncope). Risk stratification is also more accurate after observation than after ED visit alone.

Field hospital experience after 6th April 2009 L’Aquila Earthquake L. Petrazzi, R. Striuli, R. Scipioni, M. Petrarca, L. Polidoro, E. Biferi, P. Di Giosia, C. Ferri Division and School of Internal Medicine, University of L’Aquila, San Salvatore Hospital, Italy Background: Earthquakes and their sequelae are among the strongest acute and subacute psychological forms of stress (1). Further, earthquakes also induce lifestyle changes, in turn often resulting in additional stress (1). On April 6th 2009, at 03:32 AM, an earthquake reaching the magnitude of 5.8 of the Richter scale (6.3 according to U.S. Geological Survey, National Earthquake Information Center) (2) and lasting 27 s, struck L’Aquila. Our San Salvatore Hospital was damaged and evacuated. Thus, all in patients were discharged or transferred to other hospitals. A field hospital was built on the same days in the area of the San Salvatore. Aim: Aim of our study was to assess the epidemiologic impact of the earthquake and changes in pathologies at Hospital admission due to the earthquake. Methods: We conducted a case–control retrospective study articulated in: Substudy A consisting of patients admitted to the Department

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S316 of Medicine of the field hospital in the period from April 6th 2009 to May 29th 2009. Controls were the patients admitted to the same Department of the San Salvatore Hospital in the same period during the previous year. Substudy B, consisting of patients admitted to the Emergency Department of the field hospital in the period from April 6th 2009 to May 29th 2009. Controls were patients admitted to the same Department of the San Salvatore Hospital in the same period during the previous year. In substudy A age, gender, length of stay, admission and discharge diagnosis were recorded. In substudy B age, gender, triage code trend, diagnosis and outcome were recorded. Results: In substudy A (patients n. 102, controls n. 108) mean patient age was significantly higher than before the earthquake (77.01 ± 13.5 vs 67.90 ± 18.7 years, respectively; p \ 0.0001). Patients living in L’Aquila were also more common than before the earthquake (94.950 vs 85.19% respectively; p = 0,02) while mean length of stay was lower (9.40 ± 7.51 vs 12.69 ± 11.88 respectively; p = 0,02). Infectious diseases increased with the earthquake (27.18 vs 7.41%; p = 0,0001). In substudy B (patients n. 5255, controls n.6564) the yellow code significantly decreased after the earthquake (16.12 vs 45.12%; p \ 0.0001) with a significant change in the whole triage code. Cardiovascular (11.57 vs 1.14%; p \ 0.0001), psychiatric (2.21 vs 0.46%; p \ 0.0001), gynecological (4.8 vs 3.52%; p = 0.0005) and infectious (7.04 vs 1.42%; p \ 0.0001) diseases increased after the earthquake, while pneumologic (3.22 vs 10.57%; p \ 0.0001) gastroenterological (6.03 vs 8.3%; p \ 0.0001) and traumatic (31.57 vs 35.27%; p \ 0.0001) diseases decreased. Conclusions: Infectious diseases increased after the L’Aquila earthquake, particularly in the elderly patients. All of the ‘‘stress-related illnesses’’ (3) also increased, including cardiovascular and psychiatric diseases. Key factors contributing to the observed changes were likely to be related to lifestyle changes and psychological stress. Thus, our results indicate the needing to improve the health care system after natural disaster.

A case report of spasmophilia. A rare and too often forgotten disease G. A. Piccillo*, D. Santonocito**, M. Nicolosi***, E.G.M. Mondati****, P. Caponnetto****, R. Polosa****, G. Gasbarrini***** Department of Emergency Medicine*; Division of Neurology**; Division of Psychiatry*** of Cannizzaro hospital, Catania; Department of internal Medicine****, University of Catania; President of the Italian Association in Experimental Medicine*****, Italy Introduction: Spasmophilia is a very rare condition in which the patients show an abnormal sensitivity to mechanical or electric stimulation of their motor nerves conditioning in them a tendency to spasm, tetany, and convulsions (Dorland’s Dictionary). Although this condition might seem cryptic and not something which is seen daily in the practice of a physician, it affects many people in the western countries. As well as it has been observed in hypoglycaemia by Selve in General Adaptation Syndrome (GAS), in spasmophilia the body is reacting to so called stressors (sudden changes in temperature, poisoning, etc.) and in the beginning it reacts as in a shock with uncomfortable feelings, but when the action of stressors continues, the body will adapt to it, but in the final stage of the GAS, the body will succumb under the continuous strain laid upon it and (exhaustion phase), finally, the person will die. Initially the body will adapt in the course of the time, but if the action of the stressors continues too long, symptoms show up: next to tiredness and exhaustion, sweating, yawning, tachycardias, irritability, depression, phobias, etc. GAS represents the basis for spasmophilia. In this syndrome, the

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 neuromuscular over-excitability of the striped and smooth muscles plays a central role. Symptoms are represented by hyperventilation, tiredness, stiffness and twinges, muscle cramps, ticks (eyelids) and tiny muscle twitches, stomach and intestine complaints and allergies. A psychosomatic component is very usual. These symptoms seem to be quite general, but they can be specified. These patients are typically difficult ‘‘starters’’ in the morning, and in the evening they are overactive and they feel needle and pin pricks in their hands and feet and extremities heavy and stiff. Cramps show up when at rest and ameliorate during exercise. Also there may be cramps in the belly and back musculature, which initiate back and neck pain. In many cases these symptoms are connected with psychological factors. Case report: A 47-year-old woman was admitted to our Department for sudden face asymmetry, with left oral deviation, tachypolydyspnoea, tiredness, stiffness and twinges, muscle cramps to right foot, tick of right eyelids, muscle twitches, tiredness and exhaustion, sweating, yawning, cardiopalmus, irritability, depression and multiple phobias. She had been many times admitted to various hospitals with the same symptoms, submitted for this reason one more time to brainCT scan, and discharged with diagnosis of anxious syndrome and treatment on anxiolytics. A recent evaluation in Rome had permitted her to know the name of her own disease: spasmophilia and she had started therapy on clonazepam, calcitriol, magnesium and escitalopram per os. At admission, she appeared tachypolydyspnoic, with evident asymmetry of her face and marked left oral deviation, pale, sweat and very anxious and preoccupied for her own clinical conditions crying and strongly requesting an help. At respiratory evaluation evidence of harsh vesicular murmur. Normal AP (125/70 mmHg), HR 98 b/min; BR 20 br/min, body T (36.5Celsius); at EKG sinusal tachycardia (98 b/m). Gas analysis showed slight decrease of pH 7.319 with, pCO2 52.1 mmHg; pO2 25.9 mmHg, Anion Gap 8.3 mEq/L; cBase 0.6 mmol/L, cHCO3 23.2 mmol//L, cGly 89 mg/dL, cLac 14 mg/dL; ctHb 11.5 g/dL, mOsmc 283.7. We immediately treated our patient on O2 in Venturi mask, intravenous, steroids and magnesium sulphate, anxiolytics per os, obtaining the full control of all the symptoms. Laboratory data pointed out WBC 6,520/mmc, RBC 4.370.000/mmc, HGB 11.8 g/dl, MCV 87.2 fl, MCH 27 pg, MCHC 31 g/dl, PLT 242.000/mmc, N 62.3%, LY 32.11%, EO 1.63%, MO 3.36%, BA 0.5%; normal glycaemia, urea, creatinine, serum electrolytes (Ca, Na, K, Mg, Cl), CPK, myoglobin, LDH, transaminases, GGT, bilirubin, pancreatic enzymes and emocoagulative parameters. Gas analysis showed slight decrease of pH 7.319 with, pCO2 52.1 mmHg; pO2 25.9 mmHg, Anion Gap 8.3 mEq/L; cBase 0.6 mmol/L, cHCO3 23.2 mmol//L, cGlly 89 mg/dL, cLac 14 mg/dL; ctHb 11.5 g/dL, mOsmc 283.7. Brain CTscan no revealed any pathology as well as electromyography. Psychiatric and Neurological evaluation confirmed the diagnosis of spasmophilia and the patient was discharged 2 days later in quite good clinical conditions with the suggestion to submit herself to psychotherapy. Discussion: There are differences between the behaviour of spasmophilic man and woman. The spasmophilic woman has a submissive, victim-like attitude, keeping back her emotions. The man reacts in another way. He is supercritical and rationalizes continuously, hiding in this way his emotions. Introversion is a general characteristic. Constriction of the chest, accompanied by fear, is a common complaint of the spasmophilic patient. These attacks can be very annoying for them and are caused by spasms of the smooth musculature of the upper gastro-intestinal tract. Spasms in the gall ducts result in nausea and tendency to vomit. In the lower intestinal region, spasmophilia gives constipation, alternated with diarrhoea. Women may have functional menstruation complaints, like haemorrhagia and pain. Finally, as part of the spasmophilic syndrome, there must be mentioned allergies, asthma, and eczema. Therapy consists in interruption of over-excitability of the musculature. Since it is underlie by an imbalance in the mineral reserve especially of magnesium, calcium and potassium, magnesium supplementation is a

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 major part of the therapy. Vitamin B6 (100 mg) supports serotonin metabolism, and the absorption and the cellular uptake of magnesiumL-tryptophane (3 g daily) is indicated in case of acute stress as well as a proper diet. Physical exercise, massage to relax the muscles and some kind of psychotherapy is very help.

Smith-Lemli-Opitz syndrome and myelodysplasia: an unusual association complicated by acute pneumonia G. A. Piccillo*, G. Liberti**, A. Aliffi**, F. Aranzulla***, G. Pappalardo***, E.G.M. Mondati****, P. Caponnetto****, R. Polosa****, G. Gasbarrini***** *Department of Emergency Medicine; **Infectious Diseases Division; ***Intensive Care Unit of Cannizzaro Hospital, Catania; ****Department of Internal Medicine, University of Catania; *****President of the Italian Association in Experimental Medicine, Italy Introduction: Smith-Lemli-Opitz syndrome (SLO) is a developmental disorder that affects many parts of the body. This condition is characterised by distinctive facial features, microcephaly, intellectual disability or learning problems, and behavioral problems. Affected children have the characteristic features of autism with compromised communication and social interaction, malformations of the heart, lungs, kidneys, gastrointestinal tract and genitalia and can present syndactyly or polydactyly. Subjects with Smith-Lemli-Opitz syndrome have muscle hypotonia, experience feeding difficulties and grow more slowly than other infants. The signs and symptoms of Smith-Lemli-Opitz syndrome vary widely. Mildly affected individuals may have only minor physical abnormalities with learning and behavioral problems. Severe cases can be life-threatening and involve profound intellectual disability and major physical abnormalities. The syndrome affects an estimated 1 in 20.000 to 60.000 newborns and it is most common in European Caucasians while it is very rare among African and Asian populations. Mutations in the DHCR7 gene, which provides for synthesis of the enzyme 7-dehydrocholesterol reductase, which provides for synthesis of the enzyme 7-dehydrocholesterol reductase, inherited in an autosomal recessive pattern, cause SmithLemli-Opitz syndrome. The involved enzyme is responsible for the final step in the production of cholesterol necessary for normal embryonic development being a structural component of cell membranes and myelin. Case report: A 27 year-old man afflicted with Smith-Lemli-Opitz syndrome, was admitted to our Department for severe asthenia, deep anaemia and cough with fever since 1 week. Three weeks prior to presentation, he was afflicted with an upper respiratory infection with cough and fever. He exhibited a typical facial alterations, deeply pale with dehydrated skin and mucosas his speech and co-operation was mildly. Laboratory data showed moderate anaemia (RBC 2.031.000/mmc, Hb 9.4 g/dl, Hct 28.4%, MCV 85.7 fl), iron 68 lg/dl, ferritin 150 ng/ml, and leukopenia (WBC 2.100/mmc; N 43.3%, L 45.8%), rise of LDH; increase of a-2-globulins, ESR (130 mm/hour), PCR (6) and fibrinogen (683 mg/dl). Negative resulted B and C-hepatitis markers and BK.It was evaluated the antibodies IgM anti: Coxackie B1-type, Rosolia, CMV, Echo type 7, Measles, HSV 1, HSV 2, Lysteria Monocytogenes 1/2a, Lysteria Monocytogenes 4b, Adenovirus type 3, HIV, EBV, Parotitis, Borrelia Afzelii, Borrelia Garinii; Burgdorferi and Toxoplasma Gondii which resulted negative. On the contrary the research of Haemophylus influenzae was positive. Chest-X-ray revealed the presence of an extensive hypodense lesion in the left side as in acute pneumonia. We administered ceftriaxone and tachipirina intravenous obtaining the resolution of fever and severe dyspnoea (the patient was allergic to penicillin). But a

S317 radiographic control of his chest 7 days after, showed the persistence of infiltrates covering the left upper, middle, and lower lobes and the right basal lobe. A systemic, antimicrobial treatment of levofloxacin (500 mg/day) and teicoplanin (400 mg/day) was continued. Three months earlier, he had received erythromycin, inhaled salbutamol and glucocorticoids due to a tracheobronchitis and 2 months before he became ill, he was treated on oral moxifloxacin for 5 days for pharyngitis. During his hospital stay, the patient’s clinical condition worsened. Ventilation and perfusion scintiphotographs with Tc99 m, an echocardiograph, and a high resolution thoracic scan were performed in an effort to identify another illness or a possible nondrained focus; results were negative. After 7 hospital days of systemic levofloxacin therapy, his clinical condition had not improved. Two blood cultures taken after an episode of fever with a temperature of 38.5C showed that H. influenzae was resistant to fluoroquinolones (strain 32602). Treatment was switched to chloramphenicol (1 g/6 h), to which the strain was susceptible. However, on the same day as the treatment change, the patient was intubated during a severe episode of respiratory impairment and transferred to the Intensive Care Unit. The patient ameliorated within 48 h. One day later he was extubated and, 1 week later, discharged. Discussion: The myelodysplastic syndromes (MDS, formerly known as ‘‘preleukemia’’) are a diverse collection of hematological conditions that involve ineffective production (dysplasia) of the myeloid class of blood cells. Patients with MDS often develop severe anemia and require frequent blood transfusions. In most cases, the disease gradually gets worse and the patient develops cytopenias due to progressive bone marrow failure. In about one-third of patients with MDS, the disease transforms into acute mylogenous leukemia (AML), usually within months to a few years. The best prognosis is seen with refractory anemia with ringed sideroblasts and refractory anemia, where some non-transplant patients live more than a decade (the average is on the order of three to 5 years, although long-term remission is possible if a bone marrow transplant is successful). The median age at diagnosis of a MDS is between 60 and 75 years; a few patients are younger than 50; MDS diagnoses are rare in children. Males are slightly more commonly affected than females. Signs and symptoms are nonspecific and generally related to the blood cytopenias with chronic tiredness, shortness of breath, chilled sensation, sometimes chest pain due to anemia, increased susceptibility to infection due to neutropenia, increased susceptibility to bleeding, ecchymosis, purpura and petechia. Our unlucky patient presented both rare syndromes, S-L-O syndrome and MSD with consequent severe complications. This report represent our tribute to the unfortunated cases in which we diagnose an overlap between rare and serious illnesses.

A very difficult diagnosis: the Alibert-Bazin syndrome G. A. Piccillo*, R. De Pasquale**, E.G.M. Mondati***, P. Caponnetto***, R. Polosa***, G. Gasbarrini**** *Department of Emergency Medicine, Cannizzaro Hospital, Catania; **Division of Dermatology; ***Department of Internal Medicine, University of Catania; ****President of the Italian Association in Experimental Medicine, Italy Introduction: Mycosis fungoides, also known as Alibert-Bazin syndrome or granuloma fungoides, is the most common form of cutaneous T cell lymphoma which generally affects the skin, although it can progress internally over time. It was first described in 1806 by French dermatologist Jean Louis Marc Alibert who focused a type of non Hodgkin’s lymphoma characterised by onset of skin tumors having a mushroom-like appearance. The cause of mycosis fungoides is unknown, but it is not believed to be hereditary or genetic in the

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S318 vast majority of cases. One incident has been reported of a possible genetic link. It is not contagious. It is rare for the disease to appear before age 20, and is more common in males than females, especially over the age of 50, where the incidence of the disease does increase. The average age of onset is between 45 and 55 years of age for patients with patch and plaque disease only, but is over 60 for patients who present with tumours, erythroderma or a leukemic form also known as Se´zary syndrome. The disease is an unusual expression of CD4 T cells which are skin-associated, since they biochemically and biologically are most dynamically related to the skin. Mycosis fungoides is the most common type of Cutaneous T cell Lymphoma (CTCL), but there are many other types of CTCL not due to mycosis fungoides that are treated differently. Case report: A 72-year-old female peasant, coming from the Sicilian countryside, was admitted to our Department for the onset of fever arthralgia and many dyscromic skin lesions at neck, head, back, arms and legs characterised by the presence of crostous surfaces and purple-red in colour. In anamnesis mitral valve steno-insufficiency since 12 years and hypertension treated on diuretics and Ace-inhibitors. The laboratory data pointed out the presence of ANA positivity ([1:800) and was made diagnosis of nummular eczema and started therapy on steroids with no good response. CT-scan of thorax and abdomen showed the presence of mediastinal lymph nodes (max diameter 22 mm). It was performed histology evaluation of lesion biopsies that resulted consistent with lymphomatoid papulosis. Due to cardiac risk mitral valve replacement was performed but 3 months later the patient presented with fever and priginous skin lesions, mild anaemia, while lymph nodes were stable at CT scan and PET was coherent with phlogosis. We re-evaluated our first diagnosis and performed a second skin biopsy with histopathological examen, obtaining the ‘‘very’’ diagnosis of mycosis fungoides, stage IA (ISCH/EORTIC steps). The patient started therapy on PUVA with good effects. Discussion: Mycosis fungoidesis a very rare and heterogeneous disease and too often the diagnosis is, for this reason; missed. Given all this, and due to the chance of disease progression, diagnosis is mandatory. Typical visible symptoms include rash like patches, tumors, or lesions. Itching is common, perhaps in 20% of patients, and is not universal. The diagnosis is made through a combination of the clinical picture and examination, and is confirmed by biopsy. It may be sometimes difficult because the early phases of the disease often resemble eczema or even psoriasis. Diagnosis is generally accomplished through a skin biopsy and several biopsies are recommended, to be more certain of the diagnosis. Moreover, to stage the disease, various tests may be ordered, to assess nodes, blood and internal organs, but most patients present with disease apparently confined to the skin, as patches and plaques (slightly raised or ‘wrinkled’ spots). Common treatments include simple sunlight, ultraviolet light PUVA, topical steroids, topical and systemic chemotherapies, local superficial radiotherapy, the histone deacetylase inhibitor vorinostat, total skin electron beam radiation, and systemic therapies (e.g. interferons, retinoids, rexinoids) or biological therapies. Treatments are often used in combination. It is incurable, but many patients experience prolonged periods of disease-control. Prognosis depends on the disease stage: overall 5-year survival rate for mycosis fungoides is 75% (in particular it is 93% for stage A; 79% for stage B, and 44% for stage C disease).

Inappropriate visits in emergency department. experience of 5 years in a small regional hospital G. Raimondi*, B. Scordamaglia*, S. Verkhovskaia*, F. Farina*, G. Farina** *Dip. Scienze e Biotenologie Medico-Chirurgiche. Sapienza, Universita` di Roma; **Ospedale ‘‘A. Fiorini’’ ASL Latina, Italy

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Triage is defined as sorting and allocating treatment to patients based upon the severity of their conditions and it is an essential function in Emergency Departments (ED), where many patients may present simultaneously. Triage drift is a controversial practice because life and death decisions are left to the subjective determinations of nurses in high-stress situations. In addiction, there is an issue concerning the cost and efficiency of the system because of the crowding of ED, not always due to the needs of the patients. The scenario in which we are addressing the most interesting developments is the management of the inappropriate access of non-urgent or low complexity care cases. The inappropriate visits influence the ED activities, increasing the waiting times, and failing to ensure proper distribution of human, structural and economic resources. Moreover, a high number of people will involve the ED influencing as well many other units (laboratory tests, radiology, consultation services, and administrative units). This research was carried out to see if inappropriate visits to the ED of the regional hospital constituted an overcrowding factor that caused difficulties in the delivery of care. Our analysis has focused on the patients observed in the ED of the Hospital ‘‘A. Fiorini’’ (Terracina), ASL Latina. Since 2006 this hospital has had a significant increase of activity due to the inclusion of some operative units of the University of Rome ‘‘Sapienza’’. The table shows the color codes assigned in the years 2006–2010.

Year RED YELLOW GREEN WITHE TOTAL G + % W G+ W 2006 245

6289

20761

3167

30462

23928 78.5

2007 208

6309

16491

4512

27520

21003 76.3

2008 265

6698

17436

5795

30194

23231 77.0

2009 339

7992

18916

5115

32362

24031 74.2

2010 378

8807

19045

6109

34339

25154 73.2

In the analyzed years there were on average about 80 visits per day. The results indicate that the greater percentage of the visits is represented by green codes in all considered years. Codes Red and Yellow are virtually super imposable in the first 3 years, while we observed an increase in 2009 and 2010. The percentage distribution of the codes is similar in each year under review. The Red Code is less about 1%, the Yellow Code is over 20% and the sum of green and withe codes represents about 75% of the visits in the ED;. even if we can observe a costant increase, in absolute values, from 2006 to 2010 paricularly due to withe codes (from 3187 in the 2006 to 6109 in the 2010). The main causes of overcrowding in the Italian ED are attributable to several factors including: the increasing lack of confidence in the General Practitioners, the waiting times which are excessively long for specialist outpatient services and diagnostic tests, the increasing size of population not included in the National Health Service, the evolution in the organization of ED as a genuine unit of diagnosis and treatment, and the closure of small hospitals with the consequent reduction in the number of available ED. Certainly some of the inappropriate access is due to opportunistic reasons, such as immediately obtaining a benefit (X-rays, ultrasound, laboratory tests, etc.) In conclusion, the medical territorial model does not always provide an adequate response to the needs of the citizen. It is necessary to reorganize the emergency services through different models and high flexibility and at the same time with further developments of

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 integrated multi-professional activities, adaptable to different local contexts: metropolitan, urban and suburban.

Sonic boom—on the importance of timely diagnosis and management with point-of care ultrasound in a patient presenting for fever F. Simoni, N. Vitturi, G. Berti de Marinis, M. Arboit and G. Realdi Policlinico Universitario di Padova, Clinica Medica I, Padova, Italy A 75-year-old women was admitted to our clinic because of fever. Her symptoms had begun 1 week earlier, when she began complaining of fever that was continuous, initially responsive to acetaminophen and associated with worsening weakness and mild pain localized to the left flank. She denied cephalgia, cough, dyspnea, chest or abdominal pain, diarrhea, dysuria or pollakiuria. She had not recently been in contact with people with similar symptoms, she had not undergone invasive procedures. Her medical history included impaired fasting glucose, chronic hepatitis C virus infection. On initial physical evaluation blood pressure was 90/50 mmHg, heart rate was 105 beats per minute, respiratory rate was 24 breaths a minute, body temperature was 37,1C, oxygen saturation by pulse oximetry was 95% while breathing room air; she was oriented, alert, slightly confused but collaborative; the reminder of the physical examination was unrevealing. A urinary catheter was placed and urinary output was only 50 cc in the first 4 h. Laboratory-test results performed in the emergency department showed augmented inflammatory markers (white blood cell count 28,66 9 10.9/L, CRP 100,00 mg/L). A working diagnosis of severe sepsis was made. While initiating resuscitation with intravenous crystalloids we performed immediate imaging studies to evaluate the specific site of infection. The clinical assessment on admission was therefore completed by a point-of-care ultrasound examination with a portable device by the on-call resident: at ultrasound assessment the left kidney had a markedly dilated renal pelvis with echogenous content and thickened walls, no renal stones were evident, the reminder of the ultrasound examination was normal. A second working diagnosis of renal abscess complicated by severe sepsis was made. Intravenous antibiotic therapy with levofloxacin was started just after obtaining two blood cultures and urine culture. In the following hours the patient was poorly responsive to fluid therapy so vasopressors (dopamine) were started obtaining adequate arterial pressure values. 12 h after admission the hemodynamic picture was stabilized and the patient could therefore be transported to the radiology department to perform a computed tomography of the abdomen; the exam confirmed marked hydronephrosis of the lower chalices with dense content and thickened walls, no renal stones were evident and mild abdominal effusion was showed. 18 h after admission the patient underwent ultrasound-guided percutaneous nephrostomy, which was performed with a subcostal approach at the left posterior axillary line with an 8F drainage catheter: the procedure was well tolerated with no immediate complications and the purulent drainage fluid was sent for culture. In the following hours and days the hemodynamic picture improved, the patient remained afebrile, vasopressors could be tapered off and stopped on the third day after admission, laboratory test paralleled the clinical improvement. Blood and urine cultures grew an E. Coli which was sensible to the chosen antibiotic. After urologic consultation a helical CT with threedimensional reconstruction was required to plan subsequent surgical correction: the exam showed a left incomplete duplicated collecting system associated with left lower pole pelvi-ureteric junction obstruction which was actually the site of infection. This case highlights the usefulness of point-of care ultrasound in timely management of a critically ill patient. In particular ultrasound imaging allowed timely diagnosis of the site of infection and

S319 ultrasound procedural guidance was used to perform a safe abscess drainage. International sepsis guidelines recommend that all patients presenting with severe sepsis be evaluated for the presence of a focus on infection amenable to source control measures: although CT might be more accurate in identifying the site of infection, time and resource limits and first of all the danger to transport an unstable patient to a CT unit, often weight against this technique and delay its performance to when clinical stability is obtained. For this reason bedside studies, such as ultrasound, are particularly attractive in these circumstances. The same guidelines also state that, when source control is required, the effective intervention associated with the least physiologic insult should be employed: ultrasound guidance can improve success and decrease complications in these procedures. While ultrasound is still underutilized in routine care, interest in ultrasound evaluation performed directly by the physician taking care of the patient is visibly growing: on the basis of personal experience and growing evidence in the literature we believe that such enthusiasm is well justified.

Cardiovascular and cerebrovascular events pre and post earthquake of April 6th 2009. The Abruzzo experience S. Sofia1, A. Melone1, PP. Vittorini1, G. Halasz1, E. Varrato1, R. Di Filippo1, C. Balsano1,2* 1

Dipartimento di Medicina Interna e Sanita` Pubblica (MISP), Coppito, L’Aquila, Italy; 2Laboratory of Molecular virology and Oncology, Fondazione Andrea Cesalpino, Rome, Italy Objectives and background: Since international data demonstrate that acute vascular events increase after earthquakes we decided to investigate the potential increase in cardiovascular or cerebrovascular diseases in the population living in the ‘‘crater area’’ (several medieval hill towns near to the epicentrum) after the earthquake occurred in Abruzzo Region on 6th April 2009. Methods: We analyzed 10.833 patients of both sexes and all ages. We considered patients hospitalized for cardiovascular or cerebrovascular diseases over two periods of time (3 months each), before and after earthquake. We reviewed a total of 6928 cardiovascular events and 3905 cerebrovascular events, taking into account the Diagnosis Related Group (DRG). The population was divided into 3 classes of age: 0–18 (group A), 18–65 (group B) and over 65 (group C). Statistical analysis was performed by Fisher Exact Test. Results: In the post-earthquake period an increase in hospital admissions for heart related diseases in the local health department of L’Aquila more than in the other local health departments of the Region was observed. The increase in cardiovascular diseases was statistically significant in the group C in patients of the ‘‘crater area’’. About admissions for cerebrovascular diseases no statistically significant changes were found, except for Ischemic Stroke and Transient Ischemic Attack (T.I.A.) in the group C in local health department of L’Aquila. Interestingly, an increase in Hypertensive Encephalopathy was reported in all the local health departments. Conclusions: In the Abruzzo Region the earthquake induced an increase in cardiovascular and cerebrovascular diseases. Our data indicate that after a natural disaster elderly people (over 65) must be closely monitored over a period of at least 3 months.

A usual abdominal pain in a young male? A. Spinella1, G.S. Pezzuto2, M.T. Mascia3, A. Luciani2 1

Azienda Ospedaliero-Universitaria Policlinico di Modena; Reumatologia, Pronto Soccorso e Medicina d’Urgenza; 3 Immunoreumatologia, Modena, Italy 2

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S320 Case presentation: A 17-year-old Italian boy was hospitalized from the Emergency Room in the Department of Medicine in September 2010. Clinical picture at the admission was an acute diffused abdominal pain associated with fever (up to 38.5C). Except for the abdomen diffusely tender with rebound tenderness, the physical examination was unremarkable. The pain was not associated with nausea or vomiting. He also denied diarrhoea, constipation, gastrointestinal bleeding or weight loss. Biochemistry exams revealed leucocytosis and elevated acute-phase reactants. Abdominal ultrasound and abdominal and thoracic X-ray were normal. A review of patient’s medical records showed two episodes of severe abdominal pain lasted 48 to 72 h with spontaneous recovery in the childhood. Similar episodes of abdominal pain mainly in right iliac fossa associated with fever (37–38.5C) happened over the previous 2 years. The patient presented to the Emergency Room complaining these symptoms since February 2009. In the suspicious of acute appendicitis the patient underwent to appendectomy in November 2009 and the surgical report was that of an acute inflammation of the appendix. However, the symptoms were persistent after the surgery too: the attacks of fleeting pain recurred about once a month. Considering the complexity of the case a computed tomography of the abdomen was also made during the hospitalization. The result of CT was that of moderate oedema in small intestine walls with elevated contrast enhancement. The following examination with colonoscopy revealed terminal ileum involvement with an aspect of bowel oedema and inflammation and cobblestone appearance. Final diagnosis was terminal ileitis as inflammatory bowel diseases (IBD). Therapy with mesalazine was started. Despite the treatment a new episode of abdominal pain and fever caused an admission in the Emergency Room in October 2010 too and other examinations were made. Double-contrast barium enema was totally unremarkable and not solving, in spite of previous diagnosis. Therefore, an empirical therapy with colchicine was started in the suspicious of Familial Mediterranean Fever (FMF). Subsequently the patient reported no more attacks and a subjective well-being. In December 2010 genetic testing was made with the result of heterozygous mutations Met680Ile and Glu148Gln for MEFV gene. A positive answer to colchicine represented an indication to treatment prosecution and a definitive confirmation of FMF diagnosis. Discussion and Conclusions: Familial Mediterranean Fever (FMF) represents a pathogenetic entity not always easy to identify. It belongs to the rare group of autoinflammatory diseases. Its hard identification depends on the complicated differential diagnosis in respect to other diseases much more frequent in clinical practice. This case report aims to show how this entity is often unrecognized compared with other diagnostic hypothesis. In particular FMF often appears with clinical presentations not univocal to be explained. In 95% of all patients occur abdominal attacks, with all signs of peritonitis (inflammation of abdominal lining), and acute abdominal pain like appendicitis in the absence of alvus alterations. The similar presentation of the two clinical entities often leads to an unnecessary appendectomy. It was observed that the frequency of appendectomy found in FMF was far above the reported rate in the general population (40 vs. 12-25%) and the rate of non-inflamed appendectomies was extremely high (80 vs. 20%) 1. Macroscopic aspect of our case was that of a dilated appendix with serositis, therefore consistent with acute appendicitis indeed. For this reason misdiagnosis is a great risk especially for mixed entities. The peculiar and confounding factor was the endoscopic aspect similar to terminal ileitis. Inflamed mucosa of terminal ileum with oedema, lymphoplasmacellular infiltrates and cobblestone appearance is usually consistent with IBD. On the contrary FMF usually involves peritoneum and other serosal membranes with the aspect of sterile sierositis, while inflammatory bowel involvement is unusual. It is possible in our patient an overlap pathology. Although in small cohort, disease-causing MEFV mutations and FMF disease rate were

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 increased among patients with IBD. Therefore it is possible that mutations in the MEFV gene could be an additional susceptibility genetic factor in order to establish unexpected and overlapped clinical presentations in the following diseases: IBD, Behc¸et’s disease, Rheumatoid arthritis. However, in our patient, the positive answer to colchicine was essential. Reference 1. Lidar M, Doron A, Kedem R, Yosepovich A, Langevitz P, Livneh A. ‘‘Appendectomy in familial Mediterranean fever: clinical, genetic and pathological findings’’. Clin Exp Rheumatol. 2008 Jul-Aug; 26(4): 568-73

Thyrotoxic hypokalemic periodic paralysis (THPP): a challange for the internal medicine physician F. Stella*§, L. Gottardo*, S. Pianetti*, M. Busetto*, A. Semplicini*§ * Medicina Interna 1, Ospedale SS. Giovanni e Paolo di Venezia; § Dipartimento di Medicina Clinica e Sperimentale, Universita` di Padova, Italy Thyrotoxic hypokalemic periodic paralysis (THPP) is an emergency showing up with sudden onset of acute muscle hypo-asthenia associated with hypokalemia, due to sudden intracellular potassium shift. It develops in 2–3% of thyrotoxic Asian patients. It is often undiagnosed in Western countries because of subclinical thyrotoxicosis at onset. Polymorphism of the CACNA1S gene (coding for a calcium channel) has been demonstrated in Asiatic THPP patients; the genetic pattern in Western patients is unknown. Standard treatment includes b-blockers and thyrostatic drugs. Hypokalemia should not be treated with high potassium doses due to the risk of hyperkalemic rebound We report the clinical outline in a 43 year old Caucasian man presenting at ED with onset of tetraparesis. EKG and blood gas analysis were unremarkable, but serum potassium was 1,9 mEq/L. Clinical examination revealed only tetraparesis affecting the lower limbs more than the upper. Slow potassium infusion was administered. On day 3, because of the evidence of high T3 and T4 levels with suppressed TSH. b-blocking and thyrostatic therapy was administered with complete regression of all the neurological signs. This clinical case, the third reported in an asymptomatic hyperthyroid Caucasian, underlines the importance of studying thyroid function in case of hyokalemic paralysis.

A case of Takotsubo Cardiomyopathy M. Suppa, E. Contu, F. Cavicchi, C. Petroni. E. Magnanelli, S. Negri, E. Migliozzi, E. Baldini, M. Colzi, D. Curcio, A. Coppola, M.G. Scarpellini Dipartimento di Emergenza Universita` degli Studi ‘‘Sapienza’’, Roma, Italy Case report: A 75 year-old woman presented to the emergency room 2 hours after acute onset of chest pain Symptoms started because she have a sleeping night for hip pain for arthrosis She past medical story was significant for hypertension, mitral valvuloplastic, gastritis; she been taking digoxin, ace-inhibitor, beta blocker. On arrival blood pressure was 120/90 mmHg and heart rate was 80 beats/min. On cardiac auscultation no murmurs, rubs or gallops were appreciated Respiratory crackles were heard in left lung field. The electrocardiogram showed sinus rhythm deep T wave in the leads V2 to V6.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 A chest X ray showed result of median sternotomy; accentuation of broncho vascular plot, cardiac profiles within the upper range. Emergent coronary angiography revealed normal coronary arteries. Left ventriculography showed distal anterior, apical and distal inferior akinesis with hyperkinesis of the remaining walls. Peak serum troponin T was mildly elevated at 0,34 ng/ml, the serum creatinine kinase remained within normal limits with subfractions elevated at 7,7 ng/ml. Over next days she showed a marked clinical improvement. Discussion: Takotsubo cardiomyopathy was first recognized and described in the Japanese literature in 1990 by Satoh who propose the term takotsubo, a Japanese for octopus trap, cardiomyopathy for its appearance of narrow and rounded bottom on the end-systolic left ventriculography. This syndrome has also been called left ventricular apical ballooning syndrome and several case have been reported in the United States and Europe Clinical manifestation is characterized by reversible balloon-like myopathy ventricular apical wall motion abnormality with hypercontraction of basal segment, minimal evidence of epicardial coronary artery obstruction, limited myocardial enzyme release relative to the extent of wall motion abnormalities, an induction by physical or emotional stress in most cases. The prognosis of takotsubo cardiomyopathy tend to be benign. In their case series reported an in hospital mortality rate of 1% Prompt recognition of this syndrome and aggressive management with pharmacologic agents are important to favorable prognosis of this syndrome.

A strange case of anemia M. Suppa, E. Magnanelli, E. Migliozzi, S. Negri, F. Cavicchi, E. Contu, C. Petroni, M. Colzi, A. Coppola, M.G. Scarpellini Dipartimento di Emergenza Universita` degli Studi ‘‘Sapienza’’, Roma, Italy Case report: A 57 year-old man, an agonistic runner, is admitted at the emergency room for onset of dyspnea and low fever from about a week and dark urine. Remote pathological anamnesis: hypertension treated with the angiotensin receptor blockers and diuretics, dislipidemia; recent pathological anamnesis: mitral valvuloplastic made with technique of quadrangular resection of posterior leaflet and implantation of Cosgrove band no. 30. At discharge from the surgery ward, the CBC shows: RBC 3.5/mmc, Hb 10 g/dL, Ht 30.2%, LDH 746 U/L, WBC 14560/mmc, Neutrophils 84%, Lymphocytes 9.4%, PTT 1.08 s, INR 1.34, AT-III 75 mg/dl, Fibrinogen 560 mg/dl, BUN 24 mg/dl, Creatinine-kinase 1224 U/L, CK-MB 52.8 U/L, Myoglobin 376 mg/ml, GOT 47 U/L, Total Bilirubin 0,94 mg/dl, Direct Bilirubin 0,32 mg/dl, hypoalbuminemia, T-troponin 0,44 ng/ml. On physical examination the patient appears dyspnoic (respiratory rate: 28/min), pale, with systolic murmur 3/6 at the centrum and Oxygen Saturation 86% in normal air, blood pressure about 140/90. Subsequent CBC shows: RBC 1,92/mmc, Hb 5,9 g/dl, LDH 2614 U/l, Neutrophils 70,3%, Lymphocytes 19,8%, Total Bilirubin 1,91 mg/dl, Direct Bilirubin 0,59 mg/dl, Fibrinogen 554 mg/dl, GOT 147 U/l, Ferritin 316 ng/ml, negative Coombs test. Urinalysis shows ‘‘cloudy appearance, proteinuria and haemoglobinuria; in the sediment: Red Blood Cells (10 pcm), Leucocytes (20 pcm), numerous bacteria, numerous urate crystals, some hyaline casts and some amorphous urate’’. In the meanwhile blood cultures are performed which highlight a positivity for Staphylococcus Warneri and then the infectious disease doctor suggests a specific antibiotic therapy. Due to his severe anemia, the patient undergoes the transfusion of two blood bags after which the Hb is 10,4 g/dl and RBC are 3,5/mmc. Renal and bladder ultrasonography shows kidneys echotexture and size within normal limits,

S321 with preservated cortico-medullary ratio and absence of patterns related to gallstone concretions; no evidence of bilateral calico-pielical expansion; the bladder is free of wall and intraluminal alterations; no evidence of free fluid in the explored peritoneal recesses; Douglas’ recess free from pathological evidence.’’The ECG shows: sinusal rhythm, PR into normal range, signs of left ventricular hypertrophy. The chest X-ray shows ‘‘results of median sternotomy; episodes of impaired ventilation in the middle-basal left lung. Accentuation of bronchovascular plot, mainly in hilo-parailar and in middle-basal in both lungs. Accentuated hilums. Cardiac profiles within the upper range. Left chostofrenic sinus less expanded’’. The transesophageal ultrasonography shows ‘‘dialated left ventricle, with normal parietal kinesis. Dilated left atrium. No shunt in the interatrial septum. No thrombosis phenomena in both atrium. Severe mitralic failure (++++), with regurgitation in the left pulmonar veins, because of the disfunction of the posterior leaflet, due to the detachment of the prosthetic ring in the omolateral portion. Normal aorta in the ascending, arcum and descending tract, with minimal parietal thickening. Normal pulmonar artery’’. The patient was hospitalized again in the CCH ward, where he undergoes the transfusion of three blood bags; due to suspected bacterial endocarditis, serial blood cultures and empirical antibiotic therapy with gentamicin and vancomycin were performed; vancomycin was suspended for the appearance of erythematous rash on the chest. Then the patient undergoes the valve replacement with St. Jude mechanical implant no. 31. On the fourth postoperative day, routine blood chemistry analysis shows the anemia in resolution phase (Hb 11.6 mg/dl, WBC 4.3/mm3) and a normal setclotting. A transthoracic ultrasonography shows ‘‘dilatation of the left ventricle, with normal parietal kinesis. Mild pericardial effusion, left atrial dilatation, mitral valve prosthesis with normal systolic and diastolic excursion’’. The patient is discharged in good hemodynamic stability; he then goes back to his normal competitive activity, and now he’s in good health. Discussion: It’s here described the case of a patient who underwent a mitralic valvuloplastic for severe mitralic failure due to cordal disease; after this surgery, he had an anemia due to the artificial chord dehiscence. The best surgery for the correction of mitral failure is represented by mitral valvuloplastic; in the 85–95% of cases the duration of the proper functioning of the repaired valve is equal to 10 years. In case of rheumatic disease alterations or myocardial ischaemia, this kind of surgery is not indicated because these conditions could be able to have an evolution and a recurrence too.

NGAL, malnutrition and kidney injury risk A. Tonzuso, G. Carpinteri, G. Fabio Martines, C. Pirri, F. Trovato, S. Toro, D. Catalano e Guglielmo Trovato MCAU e Diagnostica e Terapia Medica–Azienda OspedalieroUniversitaria ‘‘Policlinico-Vittorio Emanuele’’, Universita` di Catania, Catania, Italy Among the new biomarkers of acute kidney injury, NGAL (neutrophil gelatinase-associated lipocalin) seems one of the most useful even in the emergency room. Nonetheless, its predictive value for severe acute kidney injury (AKI) is still uncertain. The higher frequency of acute kidney injury in patients arriving in the emergency department is one of the main factors that lead to an increase of length of hospitalization and mortality and hence to more prolonged and higher health care costs. Although there are enough validated criteria for the definition of the stages of renal damage (AKIN classification, stages 1-3) or with the RIFLE criteria (that define five classes), there are no reliable criteria of predictability and risk. Despite NGAL thresholds’ predictor for subsequent acute kidney injury have been defined in

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S322 various disease, unfortunately studies that define the actual risk in the subset of baseline normal renal function values are still few. The aim of this study, is the assessment, in subjects without a previous history of chronic renal failure, the degree of risk of renal injury-failure associated with abnormal baseline NGAL. Patients and Methods: We studied 115 patients (M 64, D 51), mean age 74.71 ± 11.07 years that, at the time of presentation-triage in the emergency department, were classified as maximum or high priority for critical respiratory events and dyspnea. Patients with actual or previous chronic renal failure (GFR [ 90) before the current admission, patients with cancer, obesity (BMI [ 30), moderate to severe anemia (Hb \11 g/dl) and fever, body temperature [38.5C were excluded. All patients were followed with clinical monitoring, routine emergency blood tests, continuous blood pressure and ECG monitoring. Chest x-ray and echocardiograms were performed at the admission, and subsequently, whenever indicated. Baseline serum NGAL was assayed, and was thereafter checked at 6, 12, 24, 48 and 72 h. Statistical Analysis: the degree of risk (Odds ratio) for acute kidney injury was defined as a GFR decrease below 60; correlation analysis vs. GFR changes of NGAL and of BMI, BNP, age and serum albumin were performed individually. Results: The Odds Ratio demonstrates an increased risk of kidney injury in patients with higher NGAL (Odds ratio 6.085, 95% CI 1.282 to 28.883), lower BMI (odds ratio, 3.401; 95% CI 0.883 to 13.108) and serum albumin below the normal values, and in patients with higher BNP. A significant direct correlation between NGAL and GFR was observed as well. Conclusions: Considering our results NGAL is confirmed as a valuable biomarker for acute kidney injury in patients admitted to the emergency department. The additional information provided by our study concerns the significant prognostic power of concurrent measurements related to malnutrition, and notably low albumin and underweightness.

Poisoning with calcium channel blockers: a case report L. Vitiello, A. Petrocelli, N. Narducci, N. Tufano, P.G. Crocco, M. De Roberto, D. Caputo Department of Emergency, University hospital of Salerno, Salerno, Italy In March 2011, a 20-year-old man was admitted to our Emergency Department (ED) for general malaise and abdominal fullness. Soon after arrival, he developed haemodynamic shock. His parents reported which 2 h before accidental ingesting of nimodipine in undefined dose for headache. Physiological history was norm; not pollens, drugs and food allergy. Remote history was only positive for exantema disease. Vital signs were: temperature 36.5 degrees C, pulse 40 beats/min, respiratory rate 18–20 breaths/min, systolic blood pressure 60 mmHg and oxygen saturation (SpO2) 99% on room air. Diffuse abdominal pain and hypertympanism were shown on physical exam. The electrocardiogram (ECG) revealed junctional rhythm with a ventricular rate of 40 beats/min, QRS 0,08 s and QTc 0,34 s. Atropine 1 mg i.v. was given, which increased the heart rate to 50 beats/min. Haemodynamic

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 stability was achieved with fluids, dopamine, calcium gluconate and glucagon intravenously. Laboratory was normal. After one hour, the patient was noted to have a junctional rhythm with a rate of 50 beats/ min and blood pressure of 80/60 mmHg. No additional medications were given. On hospital day 1, the electrocardiogram showed sinus bradycardia with U wave and wide, tall and tended T waves in anterior leads able to increase cardiac sympathetic activity. Chest-X-ray, abdominal ultrasound, conventional Doppler echocardiography and ECG-Holter were negative. On hospital day 2, the patient converted spontaneously to a normal sinus rhythm and was discharged approximately 72 h after presentation to the ED. The incidence of poisoning with calcium channel blockers, accidental or intentional, has increased in recent years, associated with more frequent use. The cardiovascular manifestations of the calcium channel blockers are hypotension, rhythm and conduction disturbances. The toxicity by calcium channel blockers can lead to a wide variety of manifestations in the central nervous system, gastrointestinal system, endocrine-metabolic, hematologic and respiratory systems. There is a high clinical suspicion when the following factors are present: hypotension with bradycardia, mental state disturbances, lactic acidosis, hyperglycemia, sinus pauses and refractory shock. Treatment is based on general measures of intoxication support, decreasing the drug absorption and improvement of cardiac function. Initial management of critically ill patients consists of supporting airway, breathing and circulation. The bradyarrhythmias and the depression of cardiac contractility are corrected with the use of intravenous calcium, glucagon, atropine and pacemaker. However, maintenance of adequate circulation in poisoned patients often requires a multitude of simultaneous therapies including intravenous fluids, dopamine, dobutamine, norepinephrine (noradrenaline), calcium, glucagon, phosphodiesterase inhibitors, such as amrinone, 4-aminopyridine and calcium entry promoters, high-dose insulin, a relatively new therapy, and mechanical devices. A new inotropic drug, levosimendan, should be considered in severe CCB poisoning. Charcoal hemoperfusion can be useful in the overdose of sustained release preparations, but hemodialysis is unworthy of therapeutical interest. Calcium plays a pivotal role in cardiovascular function. The flow of calcium across cell membranes is necessary for cardiac automaticity, conduction and contraction, as well as maintenance of vascular tone. CCB directly block calcium flow through L-type calcium channels found in the heart, vasculature and pancreas. Interruption of calcium fluxes leads to decreased intracellular calcium producing cardiovascular dysfunction that, in the most severe situations, results in cardiovascular collapse. Diltiazem and especially verapamil tend to produce the most hypotension, bradycardia, conduction disturbances and deaths of the CCB. Nifedipine and other dihydropyridines are generally less lethal and tend to produce sinus tachycardia instead of bradycardia with fewer conduction disturbances. This 20-yearold patient was manifested bradycardia which is a very rare manifestation (\0,01%) after ingesting of nimodipine.

Monday, October 24th 2011 Cardiovascular Diseases Prevalence of atrial fibrillation in patients with AL amyloidosis: relationship with cardiac structure, cardiac biomarkers and prognosis A. Alogna1, F. Salinaro1, R. Mussinelli1, M. Boldrini1, A. Raimondi1, G. Palladini2, P. Russo2, P. Milani2, F. Musca1, G. Merlini2, S. Perlini1,2 1 Clinica Medica II e; 2Centro per lo Studio e la Cura delle Amiloidosi Sistemiche, Fondazione IRCCS Policlinico San Matteo di Pavia, Pavia, Italy

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Introduction and aim: Primary systemic (AL) amyloidosis is a clonal plasma cell disorder in which the N-terminal fragments of monoclonal light chains form fibrils that accumulate in various organs, ultimately leading to organ dysfunction and death, that is very frequently caused associated with cardiac involvement. Previous reports of the electrocardiographic (EKG) findings in cardiac primary systemic amyloidosis underscored the presence of abnormally low voltages and pseudoinfarction patterns. Conduction abnormalities are frequent, and QTc prolongation has been reported in 1/3 to 1/2 of patients. Since cardiac amyloidosis is characterized by severe left ventricular diastolic dysfunction, an impact on atrial structure and function is expected. This may lead to atrial dilatation and dysfunction, as well as to supraventricular arrhythmias, eventually causing atrial fibrillation (AF) with all the well-known sequelae on cardiac pump function and on the risk of thromboembolism. Since little is known on this aspect of cardiac AL amyloidosis, aim of the present study was to analyze the prevalence of atrial fibrillation in this clinical setting, and to assess its prognostic value. Methods: We enrolled 295 consecutive never-treated subjects, in whom a first diagnosis of primary AL amyloidosis was concluded between 2008 and 2009. Diagnosis and assessment of organ involvement were performed according to the International Society of Amyloidosis criteria. Cardiac involvement was present in 193 out of 295 AL patients. Standard 12-leads EKGs and cardiac echo-colorDoppler data were collected at diagnosis, and prognosis was evaluated after a median follow-up of 477 days. Results: When compared with patients without cardiac amyloidosis the presence of cardiac involvement was associated with a different electrocardiographic pattern (low voltages: 63.9%; pseudonecrosis: 52.2%), and with prolonged PQ, QRS and QT intervals (p \ 0.05 for all comparisons). Overt atrio-ventricular block was present in 24.8%, and bundle branch block was evident in 28% of patients with cardiac AL. None of the AL patients without cardiac involvement showed AF. Despite higher left atrial diameters and volumes, only 14 patients presented with atrial fibrillation (prevalence 8.7%; p = 0.0177). Such a prevalence is lower than expected when compared with the available literature data on patients with diastolic heart failure (ranging from 13 to 19%). Kaplan–Meier survival analysis revealed a significantly higher mortality in the AF group when compared with the sinus rhythm group (p = 0.0001). The same trend was also confirmed in the group with cardiac involvement (p = 0.006). The presence of AF in cardiac AL patients was significantly associated with left atrial diameter, area and volume, as well as with NT-proBNP levels (p \ 0.05 for all comparisons). No association was found between the presence of AF and the presence of peripheral low voltages, pseudonecrosis, left ventricular mass and wall thickness, or echo-derived indices of diastolic (dys)function. CARDIAC DEATH

(and of the consequent left atrial enlargement) and other patients with diastolic heart failure. However, the presence of AF at diagnosis is associated with a much worse prognosis, indicating a more extensive cardiac damage despite the lack of association with the extent of amyloid deposition, as indicated by the left ventricular mass and wall thickness.

Cardiovascular abnormalities are a common findings in Klinefelter syndrome M. Arcopinto*, A.M. Marra*, A. Salzano*, E. Bobbio*, D. Celentani*, E. Bossone**, F. Ferrara*, D. Pasquali***, A. Renzullo***, L. Sacca`*, A. Cittadini* *Dipartimento Medicina Interna, Scienze Cardiovascolari ed Immunologiche, Universita` di Napoli ‘‘Federico II’’; **Dipartimento Cardiologia e Cardiochirurgia, Ospedale Universitario ‘‘Scuola Medica Salernitana’’ Salerno; ***Endocrinologia SUN Context: Several epidemiological studies have demonstrated an increased mortality from cardiovascular causes in patients with Klinefelter syndrome (KS). Little information is available about cardiovascular abnormalities in Klinefelter syndrome. Objective: Aim of the current study was to assess the cardiac structure and function, vascular reactivity, carotid intima-media thickness (CIMT) and exercise response in KS subjects. Patients and Methods: Eighteen patients with KS aged from 19 to 48 years old and eighteen age-matched controls participated in the study. All the subjects received testosterone treatment at the time of the investigation and underwent a complete Doppler echocardiographic examination, a cardiopulmonary exercise test (CPET) as well as a vascular study including measures of CIMT and endothelial function with flow-mediated dilation of the brachial artery. Results: Patients with KS exhibited a wide array of cardiovascular abnormalities including increased CIMT, impaired CPET performance (peak VO2, ml/Kg/min, 24 ± 2 vs. 35 ± 2 in controls, p \ 0.001,), and chronotropic incompetence (KS 10/18 vs. controls 2/18, p \ 0.01), defined as heart rate (HR) at peak exercise below 85% of predicted maximum HR . Conclusions: Reduction of cardiopulmonary performance and increased CIMT suggest that cardiovascular abnormalities are common finding in KS and may represent the pathophysiological underpinnings of the increased risk of dying from heart disease.

Syncope and occupational risk: Relevance in the clinical judgement before return to work and new proposal for occupational risk stratification

100

F. Barbic, L. Angaroni*, M. Orlandi*, F. Dipaola**, G. Costantino*, M. Solbiati*, D. Borleri***, R. Borchini****, F. D’adda***, M. Borella*****, A. Galli******, F. Perego*, F. Casella*, G. Casazza#, P. Seghizzi, P.G. Duca#, R. Furlan#

80 p<0.0001

60

Intern. Med. ‘‘Bolognini’’, Seriate (BG); *’’L.Sacco’’, Milano; **’’Sesto S. Giovanni’’ (MI); Occup.Med.; ***’’Riuniti’’, Bergamo; ****’’Macchi’’, Varese; Emerg. Dpt.; *****Vimercate e; ****Legnano; Med. Statist. ‘‘L.Sacco’’, Milano; Italcementi Group (BG); #University of Milan, Italy

40 Atrial Fibrillation Absent Present

20 0 0

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600 Time

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Conclusion: In cardiac amyloidosis, AF prevalence is lower than expected when considering both the extent of diastolic dysfunction

Background: Syncope is a common event in the general population accounting for up to 3% of Emergency Department visits. Among them, potential workers, that are the patients aged 18–65 years, are usually stratified as low risk subjects and promptly discharged. Data

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from our laboratory suggest that the 6 month risk of syncope recurrence is as high as 11.3% in this population. Therefore, if discharged patients return to a job task characterized by a potential increased rate of accidents, the recurrence of low risk vasovagal syncope may easily become a life threatening event. A proper clinical management of a worker suffering from syncope before returning to his/her job may have a remarkable social impact by reducing accidents and social costs. Aims: To evaluate the relevance of syncope for occupational physicians in their assessment of a worker suitability to safely attend a high risk job; To test a new methodology for an occupational risk stratification. Methods: 81 occupational physicians (OP), enrolled during a workshop on syncope, fulfilled a questionnaire addressing the relevance of syncope in their clinical routine by a score 0 = no relevance to 4 = high relevance. In addition, 5 job tasks characterized by different levels of risk for safety (1: driving without passengers; 2: toxic products handling; 3: working closed to very hot surfaces or flames; 4: performing invasive medical tasks; 5: working as a blue collar in office) were identified. For each of the 5 job tasks, occupational physicians were asked to use a Visual Analogue Scale (VAS) to assess the potential damage for a worker suffering from a loss of consciousness. Damage (D): how severe might be the maximal damage produced by sincope for the worker? (0 = no damage; 10 = very severe damage or death). Probability (P): what is the probability that a maximal damage will occur if a worker is going to faint? (0 = no probability; 10 = very high probability or certainty). P 9 D furnishes a score suitable to estimate the potential damage associated to the specific job task. Results: 63% of enrolled OP were male, 53% had a clinical experience longer than 10 years, 65% worked outside the hospital. Most of them (72%) considered syncope as a relevant symptom in their decision making, 41% often and 33% very often actively asked for that symptom. The table below summarizes the mean values of D, P e P 9 D obtained using the VAS scale for the 5 job tasks considered. 1

2

3

4

5

D damage

8,18

8,06

8,37

5,28

1,70

P probability

5,15

4,84

5,63

3,66

1,47

P9D

43,18

40,83

48,38

24,91

3,27

Conclusions: Syncope was found to be a relevant symptom in the clinical routine of most of the OP. Occupational doctors should be involved in the multidisciplinary approach of patients suffering from syncope. Despite driving is commonly considered a high risk activity in patient with syncope, our results indicate that occupational physicians tend to weight other job tasks, such as # 3 (activity closed to very hot surfaces or flames), at higher risk compared to driving. D, P and P 9 D combined with syncope recurrence risk might facilitate the occupational risk stratification of workers suffering from syncope.

Severe hypertriglyceridemia identifies metabolic syndrome in female sex M. Bellan, M. Menegatti, L. Franzosi, E. Merlotti, A. Calciati, R. Rapetti, S. Fangazio, G.P. Fra, G.P. Carnevale Schianca, M. Pirisi Ospedale Maggiore della Carita`, Novara, Italy

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The diagnosis of Metabolic Syndrome, according to the National Cholesterol Education Program Adult Treatment Panel III (ATP III), requires the presence of at least three of the following criteria: hypertension, plasma fasting glucose [ 100 mg/dl, triglycerides [ 150 mg/dl, HDL \ 40 mg/dl (\50 in females) and waist circumference [ 102 cm (88 in females). Metabolic Syndrome identifies, in both sexes, patients with a high diabetes and cardiovascular risk. It is well known that the physiopathological background of this condition is based on insulin resistance; furthermore the presence of hypertriglyceridemia suggests an alteration in glucose homeostasis. Metabolic Syndrome, such as post-menopause and diabetes mellitus, suppresses the female advantage, with respect to male sex, about cardiovascular disease. In this retrospective study, lead on the patients attending our Dysmetabolic Disease Unit, we aimed to evaluate if any clinical/ metabolic difference could be shown between the two sexes, regarding the presence of severe hypertriglyceridemia. We revised 1,685 clinical reports of non-diabetic patients (916 females), considering only patients with triglyceridemia higher than 300 mg/dl. We have included 78 cases; each patient has been tested for: plasma glucose and insulin concentration at baseline and after a oral glucose tolerance test, insulin resistance, according to HOMA (glycemia 9 insulin concentration/22.5) and lipid profile. Comparing the two groups (53 men and 25 women), women showed a significantly higher values of plasma glucose after 120’, plasma insulin values at baseline and after 120’ and HOMA. The percentage of patients affected by hypertension was similar in the two groups, while we registered, in females, a very higher rate of patients affected by prediabetes (56 vs. 39.6%, v2 = 8.9, p \ 0.01) and Metabolic Syndrome (100 vs. 66.1%, v2 = 11.1, p \ 0.001). Our data show that severe hypertriglyceridemia is associated with a significantly worst glucose homeostasis in females compared to males; furthermore, it is very unlikely that a woman with hypertriglyceridemia is not affected by Metabolic Syndrome.

Higher mortality rate in patients hospitalized for acute pulmonary embolism during weekends B. Boari, M. Pala*, A. De Giorgi*, R. Tiseo*, I. Bagnaresi*, F. Fabbian*, R. Salmi, F. Dentali^, W. Ageno^, D. Imberti, M. Gallerani, R. Manfredini* Medicina Interna Ospedaliera; *Clinica Medica; Medicina Interna ad Alta Rotazione, Azienda Ospedaliera-Universitaria di Ferrara; ^Dipartimento di Medicina Clinica, Universita` di Insubria, Varese, Italy Background: A weekly variation in the occurrence of several acute cardiovascular and cerebrovascular diseases has been clearly demonstrated; in particular, Monday seems to be a critical day for occurrence of acute myocardial infarction (AMI), cardiac arrest, sudden death, transient ischaemic attack, and stroke (1–6). In contrast, admissions to hospital during weekends (WE) is associated with an increased rate of mortality in some acute medical conditions (7–9). The management of acute pulmonary embolism (PE) is often challenging and requires specific medical expertise, diagnostic techniques and therapeutic options that may not be available in all hospitals throughout the entire week. The aim of our study was to evaluate whether or not an association exists between WD or WE admission and mortality for patients hospitalized with acute PE. Methods: Using routinely collected hospital administrative data, we examined patients discharged with a diagnosis of PE from the

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 hospitals of the Emilia-Romagna Region in Italy (January 1999– December 2009). The criterion for inclusion in the statistical analysis was PE and pulmonary infarction as the primary diagnosis (415.1 ICD-9-CM). The analysis excluded patients who had the following codes: 415.11—Iatrogenic pulmonary embolism and infarction, 415.19—Other, 639.6—PE complicating abortion, 639.6—Complications of ectopic or molar pregnancies***, 673.0–673.8—PE complicating pregnancy, childbirth, or the puerperium. Only emergency admissions in which PE was indicated as the main discharge diagnosis were extracted from the database. Admission on WE was defined as admission during the period from midnight on Friday to midnight on Sunday. The nine Italian festive days (January 1, April 25, May 1, June 2, August 15, November 2, December 8, December 25 and 26), when occurring on weekdays, were considered as WE. All other times were defined as weekdays (WD). The risk of inhospital death was calculated for admissions at the weekend and compared to weekday admissions. In order to evaluate the association between potential risk factors and the risk of PE, we used logistic regression models, and logistic regression analysis was also used to calculate the in-hospital mortality risk for all considered subgroups. A multivariable logistic regression was performed to determine the odds of in-hospital mortality on WE versus WD admission. Odds ratios (OR) and their 95% confidence intervals were reported. The survival analysis of the subgroups of patients admitted on WD or WE was performed using Cox-regression analysis data. The analysis was limited to in-hospital mortality within 30 days of hospitalization. Results: Out of a total of 26,560 PEs, 6,788 (25.6%) had been admitted during weekends. PE admissions were most frequent on Mondays (15.8%) and less frequent on Saturdays and Sundays/holidays (12.8%) (p \ 0.001). WE admissions were associated with significantly higher rates of in-hospital mortality than WD admissions (28 vs. 24.8%) (p \ 0.001) (OR 1.144, 95% CI. 1.072-1.222, p \ 0.001). The risk of WE admission and in-hospital mortality was higher after adjusting for gender, hospital characteristics, and the Charlson comorbidity index. Conclusions: Hospitalization for PE on weekends seems to be associated with a significantly higher mortality rate than on weekdays. Further research is needed to investigate the reasons for this observed difference in mortality in order to try and implement future strategies that ensure an adequate level of care throughout the entire week. References 1. Gnecchi-Ruscone T et al. Morning and Monday: critical periods for the onset of acute myocardial infarction. Eur Heart J. 1994;15:882–7 2. Peckova M et al. Weekly and seasonal variation in the incidence of cardiac arrests. Am Heart J. 1999;137:512–5 3. Arntz HR et al. Diurnal, weekly and seasonal variation of sudden death. Population-based analysis of 24,061 consecutive cases. Eur Heart J. 2000;21:315–20 4. Manfredini R et al. Temporal patterns of hospital admissions for transient ischemic attack: A retrospective population-based study in the Emilia-Romagna Region of Italy. Clin Appl Thromb Hemost. 2010;16:153–60 5. Manfredini R et al. Monday preference in onset of ischemic stroke. Am J Med. 2001;111:401–3 6. Manfredini R et al. Seasonal and weekly patterns of hospital admissions for nonfatal and fatal myocardial infarction. Am J Emerg Med. 2009;27:1097–103 7. Kostis WJ et al. Weekend versus weekday admission and mortality from myocardial infarction. N Engl J Med. 2007;356:1099–109 8. Saposnik G et al. Weekends: a dangerous time for having a stroke? Stroke. 2007;38:1211–5 9. Manfredini R et al. Day-of-week variability in the occurrence and outcome of aortic diseases: does it exist? Am J Emerg Med. 2008;26:363–6

S325 First-degree AV blocks and intraventricular conduction delays in AL amyloidosis: prevalence and prognostic value M. Boldrini1, F. Salinaro1, R. Mussinelli1, A. Alogna1, A. Raimondi1, G. Palladini2, A. Foli2, P. Milani2, F. Musca1, G. Merlini2, S. Perlini1,2 1 Clinica Medica II e; 2Centro per lo Studio e la Cura delle Amiloidosi Sistemiche, Fondazione IRCCS Policlinico San Matteo di Pavia, Pavia, Italy

Introduction and Aim: Amyloidoses include several different diseases in which misfolded proteins form insoluble amyloid fibrils that infiltrate virtually every organ system in the body. In the western countries, the most common form is AL amyloidosis, in which fibrils are composed mainly by the N-terminus of a monoclonal immunoglobulin light-chain, with an incidence of approximately 1 case per 100000 person–years. In AL patients, cardiac involvement is not only frequent but it is also the most common cause of death. Despite a high prevalence of conduction abnormalities that may be easily identified by the standard surface electrocardiogram (EKG), the clinical features and management of documented conduction system disease have been infrequently reported. Moreover, no adequate method for predicting sudden death is still available in amyloid heart disease. Aim of the present study was to evaluate the prevalence of atrioventricular block (AVB) and intraventricular blocks (IVB) in patients with cardiac AL amyloidosis, and to verify whether these findings do have prognostic implications, particularly in relation to the risk of subsequent sudden death. Methods: We enrolled all consecutive never-treated subjects undergoing extensive multiteam evaluation at the Pavia Amyloidosis Research and Treatment Center, in whom a first diagnosis of primary AL amyloidosis was concluded between 2008 and 2009. Diagnosis and assessment of organ involvement at baseline were made according to the International Society of Amyloidosis criteria. The study population included 295 consecutive patients, who were divided into two groups depending on the presence (n = 193) or absence (n = 102) of cardiac involvement. Standard 12-leads EKG and cardiac ecocolorDoppler data were collected at diagnosis, and prognosis was evaluated after a median follow up of 477 days.

CARDIAC DEATH 100 80 p=0.0295 60 40

AV or IV Block absent present

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Results: As expected, the presence of cardiac involvement was associated with a different electrocardiographic pattern (low voltages in 63.9%, pseudonecrosis in 52.2%, and strain pattern in 38.5% of patients, respectively). When compared with patients without cardiac amyloidosis, the presence of myocardial involvement was associated with prolonged PQ, QRS and QT intervals (p \ 0.05 for all). Overt AVB was present in 24.8%, and complete IVB was evident in 28% of cardiac AL patients, and the prevalence of atrio- and intra-ventricular conduction delays was significantly higher than in patients without

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S326 cardiac involvement (p = 0.0295 and p = 0.0306, respectively). Notably, none of the AVB patients had a higher than I degree AV block. After a median follow-up of 477 days, Kaplan–Meier survival analysis revealed a significantly higher mortality in the AVB group when compared with the ‘‘normal’’ PQ group (p = 0.0001). The same trend was also confirmed in the group with cardiac involvement (p = 0.0015). A significantly higher mortality was present also in the prolonged QRS group (p = 0.0111), but this result was not confirmed in the group with cardiac involvement. In the group of patients with heart involvement, the presence of AVB was significantly associated (p \ 0.05) with higher cardiac wall thickness and high values of NTproBNP, but not with troponin levels. In the same group, also IVB was associated with higher indexed left ventricular mass and wall thickness (p \ 0.05 for both), but not with NTproBNP and troponin I levels. Conclusion: The presence of any kind of conduction abnormalities as evident in a conventional 12-lead EKG should not be overlooked in the diagnostic work-up of patients with AL amyloidosis. Conduction abnormalities are not only more prevalent in cardiac AL patients, but they also have a prognostic role in predicting cardiac death. Such a prognostic stratification may be performed by a simple and cheap 12-lead EKG. Identification of any conduction abnormalities (starting from the ‘‘benign’’ I degree AV block) should therefore prompt a more accurate cardiological support during patients’ follow-up.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 catheterization and the history of iodine contrast allergy, a chest CT (without contrast agent) was performed. Interestingly, it showed a significant dilation of the main pulmonary artery (36 mm) and of the right pulmonary artery (32 mm), with caliber of the left pulmonary artery within normal values (24 mm), in the absence of other significant findings. In view of the clinical data and especially of the patient’s functional class (WHO II-III), after having obtained informed consent, sildenafil 20 mg TID was started. After 4 months the functional class has surprisingly improved (WHO I-II) despite an only slight reduction of PASP (43 mmHg). Conclusions: The case presented remembers us: 1) the importance of clinical Guidelines to define the broad spectrum of disease characteristics; in fact, despite the few cases reported of PH in patients with NF1, nowadays there is increasing awareness about this possible association; 2) the importance to clarify the precise etiopathogenetic mechanisms underlying PH in this specific subset of patients; in our case, in particular, the normal caliber of left pulmonary artery remains unexplained in front of the dilation of the main pulmonary trunk and of the right pulmonary artery; 3) that PH can occur late in the course of NF1 as reported by other Authors; 4) that response to specific PH therapy in NF1 has to be further investigated: in our case we obtained a significant improvement in functional capacity after some months of therapy with sildenafil, even if the very few cases described in literature at this moment showed limited benefits.

Pulmonary hypertension in type 1 neurofibromatosis Acute cardiogenic shock: don’t forget pheochromocytoma! S. Caravita*, V. Dadone**, M.B. Secchi*, A. Maggioni*, M. Gariboldi***, F. Dipaola****, S.C. Wu* *U.O.C. Medicina Interna; **U.O.C. Cardiologia; ***U.O.C. Radiologia, Ospedale Bassini; ****U.O.C. Medicina, Ospedale Sesto San Giovanni – Azienda Ospedaliera Istituti Clinici di Perfezionamento, Milano, Italy Introduction: Neurofibromatosis type 1 (NF1) or Von Recklinghausen disease is a genetic disorder transmitted as an autosomal dominant and fully penetrant trait. The signs and symptoms of this condition vary widely among the affected people. The disease is sometimes complicated with vasculopathies such as renovascular hypertension, myocardial infarction, cerebral infarction, ischemic bowel disease, rupture of cerebral aneurysm. Recently pulmonary arterial hypertension (PAH) has been reported in some patients with NF1, and International Guidelines on Pulmonary Hypertension have included NF1 associated pulmonary hypertension (PH) in Group 5 of the Classification, in which pulmonary hypertension is due to unclear and/or multifactorial mechanisms. We report here a case of von Recklinghausen disease in which PH was suspected in the course of pneumonia and confirmed thereafter. We also report the response to the initial specific therapy with sildenafil. Case report: A 75 years-old female with NF1 was hospitalized for pneumonia in another clinic. Her past medical history was also significant for arterial hypertension and COPD of mild degree. During the hospital stay a Doppler-echocardiogram estimated a pulmonary arterial systolic pressure (PASP) of 79 mmHg, compared with a previous an examination (3 years before), in which PAPS was reported as 53 mmHg. The patient was successfully treated for the pulmonary infection and was then referred to us for further definition of PH. Subsequent Doppler-echocardiogram performed at 1 and 3 months after the resolution of the pulmonary infection showed a stable reduction of estimated PASP, calculated as 49 mmHg, and dilation of the right atrium (with normal dimensions and function of the left heart chambers). These data, according to the current Guidelines, are indicative of likely PH. Considering the patient’s refusal to perform right heart

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S. Caravita*, S.C. Wu*, A. Maggioni*, L. Carassale**, S. Caporotundo**, M.B. Secchi*, M. Gariboldi***, B. Molteni**** *U.O.C. Medicina Interna; **U.O.C. Geriatria; ***U.O.C. Radiologia; ****U.O.C. Chirurgia, Ospedale Bassini, Azienda Ospedaliera Istituti Clinici di Perfezionamento, Milano, Italy Pheochromocytomas are rare tumors, with an often confusing array of clinical symptoms. Nevertheless there are some typical symptoms and signs which strongly suggest the clinical diagnosis of pheochromocytoma (PC). In particular, the great majority of patients have classic features: headache, palpitations, perspiration and pallor, almost all accompanied by arterial hypertension (AH). The condition is lifethreatening due to cardio-vascular complications, mainly stroke, arrhythmias and hemodynamic impairment of the heart. Unusual presentation including acute cardiogenic shock (CS), pulmonary edema (PE) and sudden death have likewise been reported. Here we present a case of reversible CS unexplained despite the diagnostic effort performed by the Intensive Care Staff, until a previously overlooked PC was discovered. Case report: A 56-year-old woman with previous diagnosis of AH (in discontinuous treatment with enalapril 20 mg/hydrochlorothiazide 12,5 mg) and of multiple sclerosis (undergone a recent course of therapy with mitoxantrone), was transported under emergency condition for persistent loss of consciousness occurred at home, to the local Hospital (H) and from here to the city main H by helicopter with the assistance of medical resuscitation staff: the diagnosis was anterior STEMI conditioning CS and PE. She had already undergone orotracheal intubation and mechanical ventilation before transport. Thrombolysis was judged inappropriate and acetylsalicylic acid and low-molecular-weight heparin were administered. Upon arrival, general conditions were extremely serious, with arterial pressure 60/40 mmHg during dopamine and crystalloid infusion, heart rate 125 beat per minute, O2 saturation 76% while breathing pure O2, GCS 3/15. The ECG showed significative ST-segment elevation in the anterior leads. Chest X-ray confirmed bilateral PE. Echo-cardiogram demonstrated severe depression of left ventricular (LV) contractility

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 (EF 20%) with diffuse wall hypokinesia. Blood examination showed: troponin I 28.19 ng/ml (normal values: \0.5), creatinine 1.6 mg/dl, K+ 2.6 mEq/L, Na+ 143 mEq/L, CK 822 U/L (26-170), CKMB 86 U/L (\13), AST 226 UI/L (13-41), ALT 91 U/L (9-63), LDH 1717 U/L (300-600), d-Dimer 1806 ng/ml (0-278). Emergency coronary angiography revealed patent coronary arteries. Intra-aortic balloon pump was introduced and maintained until the 3rd hospital day with progressive improvement of hemodynamics. On 10th day of hospital stay the patient was moved to Cardiology Ward. Here echocardiogram showed a complete normalization of LV EF. Comprehensive screening examination for the etiological definition of suspected infective myocarditis was performed. Abdomen ultrasound, performed for transitory reduction of Hb to 10.5 g/dl, revealed a mass measuring about 5 cm in diameter, interpreted as retroperitoneal hematoma. After 11 days the patient was discharged in good clinical condition. In the absence of a clear etiological diagnosis of the occurred event, the patient was given the advice to discontinue treatment with mitoxantrone for suspected cardiotoxicity. After 7 months the patient was admitted to our hospital for neuromotor rehabilitation and clinical reassessment; however an abdomen ultrasound performed after an episode of acute urinary retention revealed a left adrenal mass, confirmed by computed tomography and measuring 47 mm in diameter. Successive investigations were relevant for: urinary epinephrine 5 lg/L (0-22), norepinephrine 1415 lg/L (1285), vanilmandelic acid 25.3 mg/L (1.8-7); chromogranine 127 UI/L (0-20). After MIBG scintigraphy showing focal and intense accumulation of the radiotracer at the level of the left adrenal gland, the patient underwent surgical removal of the tumor without any complication and the histological examination confirmed the diagnosis of PC. Tumor cells stained positively chromogranin, neurofilaments, S100, NSE, synaptophysin. Conclusions: 1) even if acute cardiac failure due to highly elevated catecholamines is a rare cause of CS, the suspect of PC should always be kept in mind, especially when, as in the case presented, a clear etiopathogenesis can’t be found and when a retroperitoneal mass is incidentally discovered; 2) the postulated mitoxantrone cardiotoxicity in our case is unlikely, because of the very acute occurrence of LV dysfunction and its prompt and complete reversibility in few days; 3) it should be remembered that development of CS in PC may be due to a combination of several factors: firstly the well-known direct toxic effect of increased levels of catecholamines (as shown in autopsy studies of patients died from PC, with typical histologic characteristics), leading to impaired LV EF, secondly the subsequent development of hypotension or a coronary vasospasm, leading to impaired coronary flow.

Atherosclerosis and inflammation M.M. D’Elios, M. Benagiano, A. Amedei, C. Della Bella, E. Niccolai, D. Prisco Patologia Medica, University of Florence, Italy Observations in humans and animals led to the hypothesis that atherosclerotic plaques derive from specific cellular and molecular mechanisms that can be ascribed to an inflammatory disease of the arterial wall, whose lesions invariably consist of monocyte-derived macrophages and T lymphocytes. Activated macrophages and T cells would be responsible for in situ production of enzymes, growth factors, cytokines, and chemokines that further expand the process. If inflammation continues unabated, it results in an increased number of plaque-infiltrating macrophages and T cells, both of which emigrate from the blood and proliferate within the lesions, resulting in a remodeling of the arterial wall.

S327 A pathogenetic role for infections in atherosclerosis is suggested by the detection of pathogens in the arterial vessels and by the association between atherosclerosis and serological responses to different pathogens, such as cytomegalovirus, herpes simplex virus, Haemophilus influenzae, Chlamydia pneumoniae, and Helicobacter pylori, or between the extent of atherosclerosis and the infectious burden. However, the role of cell-mediated immunity and the functional status of pathogen-specific T cells within atherosclerotic lesions remain poorly characterized. We studied the antigen specificity and functional profile of in vivo activated T lymphocytes that infiltrate atherosclerotic plaques of thirty Helicobacter pylori-infected patients (15 males and 15 females; mean age 69.4 years) with or without anti-Chlamydia pneumoniae antibodies. In the lymphocytic infiltrates of human atherosclerotic lesions, we showed a significant (p \ 0.001) predominance of T cells producing gamma-interferon and other cytokines. We detected C. pneumoniae DNA and C. pneumoniae-specific T cells but not H. pylori-specific T cells in atherosclerotic plaques of anti-C. pneumoniae seropositive patients infected by H. pylori. Plaquederived T cell clones either specific for C. pneumoniae or with unknown specificity exhibited a production of interferon-gamma and other cytokines, helper function for tissue factor production by monocytes, proapoptotic activity, and perforin-mediated cytotoxicity. Thus, atherosclerosis, although multifactorial, can be regarded as an immuno-pathological condition, related to inflammation.

Heart failure: a new management approach in hemodynamic deterioration S. Dassi, G. D’Angelo, R. Turconi, A. Girola, S. Berra, E. Rovelli Heart Failure Unit, Garbagnate Hospital, Garbagnate Milanese, Italy With a prevalence of about 2% in the general population in Europe, reaching 10-20% in 70-80 years old, Heart Failure is a deep impact clinical syndrome of high cost for the national health system. Mortality from heart failure is around 10% per year. The prognosis nevertheless worsen after every re-hospitalization and about 50% of the patients die within 4 years from the diagnosis. With the hope to decrease the re-hospitalization rate of people with diagnosis of heart failure, we developed an integrated approach between hospital service and general practice, based on an openaccess heart failure out-patient clinic and a telemedicine service, that allowed to perform a specialist follow-up after hospital discharge. This system is addressed in particular to classes III-IV NYHA patients with a new-onset clinical deterioration. The patient is admitted if there is evidence of cardiovascular deterioration, like a new-onset arrythmia, evidence of cardiac ischemia, new-onset renal dysfunction, inadequate medical therapy or the need for a multidisciplinar approach to evaluate therapeutic management in patients with multiple comorbidity (for example COPD, renal failure and atrial fibrillation). Whether there is not a definite indication for hospitalization, we suggest instead a Day-Hospital: this has the aim to provide a specialist opinion and/or diagnostic techniques and treatments which are not normally available in general practice. During the day hospital, the patient is first of all evaluated by a nurse, that monitors all the cardiovascular variables and parameters. Then an internist will establish a personalized management plan based on the laboratory tests and the chest X-ray, ECG and echocardiogram results. Whether needed, he can ask for a specialist advice, for invasive diagnostic or therapeutic techniques (for example coronarography or

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S328 biopsy). The patient can be evaluated by a specialist, if necessary, like a cardiologist for a myocardial revascularization or a nephrologist for an ultrafiltration. Intravenous drugs can be used to improve clinical conditions quickly and in a safe environment. The Day-hospital admission aims to improve clinical conditions and restore haemodynamic balance, identifying exacerbations causes, optimizing medical therapy, avoiding adverse reactions, identifying revascularization candidates, promoting a correct selfmanagement to the patients and establishing a correct follow-up strategy. We expect to obtain both quality of life improvement and hospital source saving.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392

Basal

Medium

Apical

Bas- BasAp P Med P

MedAp P

Endocardial parameters Cycling Septum

Soccer

Basket

-14.96 ± 5.0 -15.40 ± 3.9 -19.83 ± 6.4 .02

NS.

.02

Lateral wall

-16.00 ± 5.5 -14.81 ± 4.8 -19.35 ± 5.6 NS.

NS.

.02

Septum

-14,71 ± 4.6 -17.43 ± 2.9 -20.78 ± 5.4 .001

.05

.03

Lateral wall

-16.94 ± 4.5 -18.55 ± 3.4 -18.66 ± 6.4 NS.

NS.

NS.

Septum

-15.44 ± 4.2 -16.30 ± 3.0 -20.59 ± 6.8 .01

NS.

\.01

Lateral wall

-17.97 ± 4.8 -18.74 ± 3.8 -18.74 ± 6.7 NS.

NS.

NS.

Epicardial parameters Cycling Septum

Soccer

Basket

11.69 ± 6.0 NS.

NS.

NS.

Lateral wall

-11.33 ± 3.4 -12.54 ± 3.4

-11.67 ± 5.6 -12.08 ± 4.2 -10.88 ± 4.8 NS.

NS.

NS.

Septum

-13.22 ± 4.1 -15.44 ± 3.0 -13.05 ± 4.6 NS.

NS.

NS.

Lateral wall

-13.27 ± 4.9 -14.66 ± 3.5 -10.96 ± 4.1 NS.

NS.

.01

Septum

-15.92 ± 4.3 -15.45 ± 2.8 -11.95 ± 3.8 .01

NS.

\.01

Lateral wall

-14.93 ± 7.0 -12.77 ± 7.9 -11.32 ± 3.6 NS.

NS.

NS

Left ventricle multi layer strain approach in adolescent athletes from different kinds of sport A. De Luca, L. Stefani, G. Predrizzetti, S. Pedri, G. Galanti. Sports Medicine Center, University of Florence, Italy Background: Regular training induces in athletes morphological and functional myocardial modifications, generally called ‘‘athletes heart’’, that are more evident in adults than in adolescents. In addition to the 2D standard echo parameters, the evaluation of the myocardial contractility is currently possible by deformation parameters (strain, rotation and twist). This study investigates the role of rotation and twist parameters with the objective of better characterizing the heart performance in trained adolescent athletes from different kind of sports. Eventually, early verify any possible impact due to the regular sport activity not revealed by the standard parameters. Methods: 50 adolescents competitive athletes aged 17.6±0.5 years (16 cyclists, 17 soccer players and 17 basket players), regularly trained at least three times a week for at least 9 months a year, were evaluated either by to 2D echocardiography or by a special software multi-layer approach (ESAOTE-Italy) to calculate Left Ventricle (LV) endocardial and epicardial rotation, twist, circumferential strain (CS) and longitudinal strain (LS). The data were compared by ANOVA test. Results: All the values found were within the normal range despite the LV Cardiac Mass index (CMi), the epi-CS, epi-LS, epicardial apex rotation and the Endo/Epi twist were significantly higher in cyclists only. A physiological difference of the Endo/Epi basal circumferential strain and twist values, as expression of physiological heart contractility, have been found in all the groups. A weak but not significant relationship between the Endo and Epi twist values and CMi was also reported in cyclists. Conclusions: The results are suggestive for a relationship between the progressive increase of apical LV twist and CMi. This aspect is particularly evident in adolescent practising endurance sports as cycling where the CMi is higher. The range of the values is however substantially comparable to adults. Multilayer approach completes the LV performance evaluation in adolescents athletes with an high CMi confirming normal function in them. Further studies will be necessary to compare the results with a sedentary group.

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Rosuvastatin dose-dependently reduces circulating biomarkers of vascular endothelial cells and platelet activation: the QUASAR study G. Desideri, D. Mastroiacovo, M. Pinelli, D. Grassi, G.L. Turco, G. Bafile, M. D’Elia, L. Scalisi, C. Di Girolamo, A. Camerota, G. De Blasis, A. Mezzetti, C. Ferri, F. Cipollone University of L’Aquila, Department of Internal Medicine and Public Health, University of L’Aquila, L’Aquila-Italy; Center of Excellence on Atherosclerosis, Hypertension and Dyslipidemia, University of Chieti G. d’Annunzio, Chieti; Vascular Surgery and Angiology Units, SS. Filippo and Nicola Hospital, Avezzano, Italy Current concept on atherosclerosis indicates that inflammation plays a key role in the cascade of events that eventually result in plaque erosion and fissuring. According to this hypothesis, the serum levels of acute-phase reactants are increased in patients with unstable angina and those at risk for the development of myocardial infarction or stroke. It is unknown, however, whether the serum level of acute-phase reactants truly reflects plaque inflammation or whether it reflects a state of hypercoagulability by systemic inflammation. Several clinical trials have shown repeatedly that lipid lowering can strongly reduce coronary events and mortality rates. The substantial degree of clinical benefit appears out of proportion to the relatively modest improvement of the degree of stenosis produced by similar lipid-lowering regimens in angiographic studies. These disparities suggest that hypolipidemic treatment may somehow ‘‘stabilize’’ atherosclerotic plaques in a qualitative manner independent of lesion size itself assessed by angiography. However, no studies have yet addressed if this protective effect is directly related to the intensity of LDL reduction, and therefore might be obtained at greater extend with the newest, most efficacious, rosuvastatin. Starting from these evidences we designed the qualitative analysis of plaque stability after rosuvastatin therapy in asymptomatic patients enlisted to undergo carotid andarterectomy (QUASAR study), a prospective, single center, randomized, parallel group study assessing and comparing the effects of different rosuvastatin regimens on the

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 microRNAs’ expression profile in atherosclerotic plaques and whether or not the greater reduction in LDL cholesterol as achieved by rosuvastatin produces a stronger reduction in circulating indices of inflammation. Here we are presenting data on the effects of rosuvastatin on soluble indexes of atherosclerotic inflammation. A group of 70 (male and female) hypercholesterolemic subject (Fredrickson Ila) with LDL-cholesterol [100 mg/dL, ‘‘high risk’’ according to internationally accepted criteria, enlisted to undergo endarterectomy for extracranial high-grade ICA stenosis, were randomized to either step 1 AHA diet plus rosuvastatin 10 mg/day, or step 1 AHA diet plus rosuvastatin 40 mg/day, for 8-10 weeks until the endarterectomy. Circulating levels of soluble vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, E-selectin and P-Selectin, as biomarker of proatherogenic activation of vascular endothelial cells and platelets were measured. Eleven patients were lost during the follow-up. All soluble biomarkers significantly decreased after rosuvastin treatment, being this effects significantly (p \ 0.01) more evident in patients assigned to high-dose rosuvastatin (Figure). As expected, the reduction in LDL cholesterol was more evident in patients assigned to the higher dose of rosuvastin (-51 vs. -41%, p \ 0.01). In the whole study population, a slight correlation was found between changes in LDL cholesterol and changes in circulating soluble VCAM-1 (r = 0.246, p \ 0.01) and P-selectin (r = 0.231, p \ 0.01). Taken together, our preliminary data indicate that rosuvastatin dose-dependently reduced pro-atherogenic activation of vascular endothelial cells and platelets. These effects seems to be only partially related to the reduction of LDL cholesterol levels. The QUASAR study was supported by a grant from AstraZeneca.

Autonomic profile in patients with diabetes mellitus and diastolic dysfunction A. Di Stefano, L. Borgognoni, L. Gasperini, A. Papa, A. Notturni, M. Villiva`, T. Villani, A. Paris, A. Fiorentini, L. Tubani Sapienza Universita` di Roma, Policlinico Umberto I, Dipartimento di Medicina Clinica, Roma, Italy Introduction: Diabetic cardiomyopathy has been defined as ventricular dysfunction that occurs in diabetic patients independent of a recognized cause (coronary heart disease, hypertension) A variety of derangements may contribute to ventricular dysfunction in such patients, these include autonomic neuropathy.

S329 Left ventricular diastolic dysfunction is considered a precursor of diabetic cardiomyopathy, while diabetic cardiovascular autonomic neuropathy is associated with an increased risk of mortality. This study evaluates the prevalence of LV diastolic dysfunction in a group of type 2 diabetes mellitus normotensive patients without signs of cardiovascular disease and the correlation with cardiovascular autonomic neuropathy Materials and Methods: Were enrolled 20 patients suffering from type 2 diabetes. Were excluded from the study: hypertensive patients, patients suffering from diseases of autonomic activity; taking drugs that act on autonomic nervous system; who developed macro- and micro-vascular complications. For each of the subjects enrolled was performed a 24 h electrocardiographic dynamic monitoring with analysis of HRV and standard 2D and Doppler Echocardiography. Results: In our study group 70% had diastolic dysfunction, so patients were divided in two subgroups: diabetic with diastolic dysfunction (DDD) and diabetic without diastolic dysfunction. (nDDD) Both were matched with a control group of similar age and sex. In time domain we observed a reduced global autonomic activity (SDNN) in both groups compared with controls, while there was no statistically significant difference between DDD and nDDD groups. (SDNN 24 h:DDD 110 ± 39,95; nDDD 127,37 ± 26,83; controls 169,11 ± 28,94) In addition parasympathetic activity (RMSSD) was reduced in both groups, particularly in DDD (RMMSD night DDD 32,72 ± 13,23; nDDD 36,23 ± 7,24; controls.54,05 ± 16,63) In Frequency domain has been highlighted a sympathetic hyperactivity (LF) more markedly in DDD than in nDDD not statistically significative vs control group. (LF 24 h DDD 52,24 ± 11,24; nDDD 47,05 ± 12,15; controls 57,53 ± 6,13) Analysis of parasympathetic activity (HF) showed a significant reduction in nocturnal values in DDD than nDDD and control group. (HF night DDD 41,64 ± 7,58; nDDD 51,08 ± 9,10; controls 59,25 ± 8,63) Conclusion: We have shown in our study group of normotensive diabetic patients a high prevalence of diastolic dysfunction. Autonomic activity assessed by Heart Rate Variability analysis showed in the time domain an evident impairment in the sub-groups studied compared with controls; while in the frequency domain we have shown a constant sympathetic hyperactivity in the two subgroups of patients with loss of circadian rhythm, this hyperactivity is more increased in patients with diastolic dysfunction. An interesting observation is also most marked reduction of the parasympathetic component in patients with diastolic dysfunction even compared to diabetics without diastolic dysfunction. Therefore, the presence of diastolic dysfunction is associated with greater impairment of autonomic activity affecting especially the parasympathetic component. requires a larger series in order to clarify which correlation exists between impaired parasympathetic component and diastolic dysfunction.

Cardiovascular risk factors and carotid stenosis predict cerebral haemodynamic impairment in Alzheimer’s Disease L. Falsetti1, G. Viticchi2, M. Bartolini2, L. Provinciali2 and M. Silvestrini2 1

Medicina Interna Generale e Subintensiva Azienda OspedalieroUniversitaria ‘‘Ospedali Riuniti’’, Ancona; 2Clinica di Neurologia, Dipartimento di Neuroscienze, Universita` Politecnica delle Marche, Italy

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S330 Abstract: Alzheimer’s Disease (AD) is the most common form of progressive dementia among internistic patients. Many hypotheses have been postulated for AD pathogenesis, and there is a growing but conflicting evidence about a vascular theory (1,3). Recently, we found a significant correlation between extracranial carotid atherosclerosis, intracranial vascular reactivity and mini-mental state examination (MMSE) impairment over a 12-months observation in a cohort of 442 AD patients (2). Aims: Aim of this study was to evaluate the correlation between intracranial vascular reactivity index (breath-holding index, BHI), extracranial carotid atherosclerotic involvement and classical cardiovascular risk factors, as demographic characteristics, smoking, hypertension, diabetes and dyslipidemia in a cohort of patients affected by clinically defined AD. Patients and Methods: We enrolled 745 consecutive patients followed by the dementia ward of our University Hospital (A.O.U. Ospedali Riuniti, Ancona). Each patient underwent a standardized interview about clinical history, neuropsycological evaluation, extracranial echo-color Doppler ultrasound and transcranial doppler (TCD), testing BHI for each side. We synthesized each classical risk factor and sex into a dichotomous variable; the number of risk factors affecting a single patient were collected into an ordinal variable (ranging from 0 risk factors to 4 risk factors); extracranial echo-color Doppler result was expressed into an ordinal variable, ranging from ‘‘no stenosis’’ to ‘‘bilateral haemodynamic stenosis’’. Only hemodynamically significant ([60% of the internal carotid lumen) stenoses were considered. MMSE scores, corrected for age and sex, were collected as continuous variables. Breath-holding index, calculated by dividing the percent increase in mean flow velocity occurring during breath-holding by the length of time (in seconds) subjects hold their breath after a normal inspiration, was synthesized both as a dichotomous variable (\0.69, pathologic, [0.69, normal) (3) and as an ordinal variable (normal, monolateral pathologic and bilateral pathologic). Statistical analysis was conducted with two ordinal regression models, one considering BHI as dichotomous, the other considering BHI as ordinal. Both models included the classical risk factors, the synthetic variable for the number of risk factors and the ordinal variable for extracranial echo-color Doppler results. Results have been weighted by MMSE, age and sex. Ordinal regression was calculated with SPSS 13.0 for Windows systems. Probability of each event was calculated as 1/[1 + (ea-bx)], being a the level threshold and bx the factor level. Results: The probability of a normal BHI in AD patients decreased proportionally with the increase of the number of vascular risk factors, from 95% in patients with no risk factor to 21% of patients with four risk factors (Fig. 1, p \ 0.05). Extracranial echo-color Doppler ultrasound could also predict a pathological BHI: the probability of a normal BHI decreased from 73% among patients without hemodynamically significant stenosis to 21% in patients with bilateral stenosis (Fig. 2, p \ 0.05). Each vascular risk factor was also associated with an increase of the risk of developing a pathological (monolateral or bilateral) BHI (p \ 0.05). Discussion: AD is a complex disease, and its pathogenesis, still uncleared, could be related to microvascular alterations in a favourable genetic background. Hypertension, diabetes, smoking and dyslipidemia have already been associated to AD and its progression (1). Both BHI and extracranial vessels involvement can predict a worse outcome at 12 months in MMSE, independently from specific treatment and risk factors presence (2). BHI is a suitable index for cerebral hemodynamics status, and its alteration could express the final pathway of vascular derangement in AD. Classical risk factors and extracranial haemodynamic impairment could act on intracranial circulation initiating and maintaining the cascade of events responsible of AD progression.

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Fig. 1 Predictive value of Risk Factors over BHI

Fig. 2 Predictive value of Carotid stenosis over BHI References 1. Querfurth HW, LaFerla FM. Alzheimer’s disease. N Engl J Med. 2010 Jan 28;362(4):329–44 2. Silvestrini M, Viticchi G, Falsetti L, et al. The role of carotid atherosclerosis in AD progression. J Alzheimer’s Dis (in press) 3. Silvestrini M et al. Cerebrovascular reactivity and cognitive decline in patients with AD. Stroke. 2006 Apr;37(4):1010–5

CHA2DS2-VASc and the risk of early AF relapse: another reason for rate control and anticoagulation L. Falsetti1, G. Rinaldi, A. Gentile, V. Catozzo, A. Balloni, W. Capeci, N. Tarquinio, M.S. Del Prete, G. Filippi, G. Ciotti and F. Pellegrini Dipartimento di Medicina Interna ASUR ZT7 Ancona, Osp. ‘‘SS. Benvenuto e Rocco’’ Osimo; 1Medicina Interna, Malattie ImmunoAllergiche e Res, Medicina d’Urgenza, Ospedale Torrette, Ancona, Italy Background: Atrial fibrillation (AF) is the most frequent cardiac arrhythmia observed in Internal Medicine departments. CHA2DS2VASc1 is a clinical score which summarizes the coexistence of cardiopathy, hypertension, ageing, diabetes, previous stroke, cardiovascular pathologies and sex, used in predicting the cardioembolic risk, thus representing a tool to guide the anticoagulant therapy. Aims: To evaluate if this ruler could predict early relapses of AF after an electric or pharmacologic procedure of sinus rhythm (SR) restoration. Patients and Methods: We retrospectively evaluated 220 consecutive patients admitted to our Internal Medicine Department for AF undergoing to electric or pharmacologic SR restoration. For each patient we evaluated the full history and the drugs used. Cardiovascular risk factors, presence of cardiac valve pathologies, neoplasms, current use of statins, ACE-inhibitors, angiotensin receptor blockers, loop diuretics, amiodarone and warfarin were also investigated and

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 synthesized as binary variables. CHA2DS2-VASc was calculated and used as an ordinal variable. Absence of early relapse of AF, defined as maintenance of sinus rhythm 48 h after SR restoration was defined as a binary variable. We evaluated the correlation between absence of early relapses of AF and CHA2DS2-VASc with an ordinal regression model, including hypothyroidism, cardiac valve pathologies, neoplasms and each single drug as covariates. Model fitting test resulted significant (p \ 0.0001), while Pearson and Deviance test resulted non-significant, indicating a significantly predictive model. Analysis was conducted with SPSS 13.0 for Windows systems. Results: 18 patients with spontaneous recover of SR were excluded from analysis. A final sample of 202 patients was considered. A higher predicted probability of absence of early relapses of AF was related to lower CHA2DS2-VASc values: patients without early relapses of AF had a five-fold increase (OR = 5.1; 95%CI: 3.82-6.79; p \ 0.05) of having a normal CHA2DS2-VASc score. The probability of sinus rhythm maintenance lessened significantly along with the increase of CHA2DS2-VASc score: higher classes were strongly related to a high probability of early relapses. Discussion: Non-valvular AF is a complex disease, related to electrical and mechanical remodeling of atrial myocardium. CHA2DS2VASc score, already used to assess the risk of thromboembolic events, summarizes many of the factors involved in mechanical remodeling. This index can predict the likelihood of early relapses of AF after electrical or pharmacological attempts of restoration of SR. Since restoration of SR is not a risk-free procedure, CHA2DS2-VASc could help the physician to decide both for the antithrombotic therapy and a rate-control approach in high-risk categories.

S331 Renal failure of type-2 cardio-renal syndrome is due to renal hypoperfusion secondary to heart failure and is mediated by an imbalance between vasoconstrictors and vasodilators. The decrease in glomerular filtration rate does not correlate with left ventricular ejection fraction. Aim of this study was to evaluate, by Doppler sonography, renal hemodynamic alterations in heart failure. Thirty patients (age: 51 ± 15yrs) with dilated cardiomyopathy (DCM) and 20 normal subjects (C) were studied. Cardiomyopathy was essential in 36.6%, post-ischemic in 36.6%, alcoholic in 16.7%, post-myocarditis in 10% of patients. All patients were hemodynamically stable. In each patient, Doppler-echocardiography and renal Doppler sonography (measurement of renal interlobar arterial pulsatility index) were performed the same day, together BUN, creatinine, NT-proBNP measurements. Patients with DCM had normal kidneys (morphology and volume) and LVEF was 26±6.8%. PI-K was increased compared to C (1.74 ± 0.71 vs. 0.95 ± 0.19, p \ 0.001) and also renal function was impaired (creatinine 128.5 ± 84 vs. 70 ± 30 lmol/L, p \ 0.01, BUN 11.6 ± 5.8 vs. 7 ± 1.5 mmol/L, p \ 0.01). Prevalence of renal failure was 36.6% (NYHA 1-2: 23%, NYHA 3-4: 52.9%) while prevalence of increased PI-K was 83.3% (NYHA 1-2: 69.2%, NYHA 3-4: 94.1%). PI-K was increased already in mild heart failure (NYHA 1-2) (PI-K: 1.37 ± 0.3 p \ 0,01), but more so in patients with more severe heart dysfunction (NYHA 3 e 4) (PI-K: 2,1 ± 0,8 p \ 0.01) without significant relationships with LVEF or right atrial pressure. There were no differences in creatinine or BUN among patients with different severity of heart dysfunction (creatinine 105 ± 23 vs. 140 ± 104 lmol/L, urea 10.3 ± 5.7 vs. 12.3 ± 6 mmol/L). NTproBNP was increased in patients with DCM (6249.61 ± 3.963 ng/L) and did not correlate with LVEF, PI-K, renal function, right atrial pressure. In conclusion, in patients with chronic heart failure renal vasoconstriction can be demonstrated by Doppler-sonography in the early stage, when renal function is still normal, and increases with the worsening of heart failure. Renal Doppler resistance indices may be used for early diagnosis of type-2 cardiorenal syndrome and for prevention of acute, diuretic-induced, renal failure.

The management of heart failure in a new dedicated outpatient clinic G. Gigantino*, N. Tufano**, S. De Angelis**, S. Minichiello**, E. Casoria**, P. Predotti***, A. Pipolo***, A. Lambiase***, and A. Gigantino***

Fig. 1 Risk of early AF recurrence among CHA2DS2-VASc subgroups Reference Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest. 2010 Feb;137(2):263–72. Epub 2009 Sep 17. PubMed PMID: 19762550

Evaluation by Doppler sonography or renal vasoconstriction in type-2 cardiorenal syndrome G. Silvia, P. Paola, T. Silvia, B. Paola, B. Giancarlo, B. Massimo, S. Cristiano, S. David Department of Clinical and Experimental Medicine, Clinica Medica 5, University of Padova; Institute of Cardiology, University of Padova, Italy

*Scuola di Specializzazione in Cardiologia, Seconda Universita` degli Studi di Napoli; **Dipartimento di Emergenza e Accettazione, Azienda Ospedaliera Universitaria di Salerno; ***Dipartimento Cuore, Azienda Ospedaliera Universitaria di Salerno, Salerno, Italy Introduction: Heart failure (HF) management is characterized by very high healthcare costs, mainly related to frequent hospitalizations. Guidelines1 recommend programmes which provide structured followup delivered by cardiologists and specialized nurses. Nevertheless these programmes are frequently insufficient, leading to inadequate support and suboptimal treatment2,3. Aim: to retrospectively analyze successes and failures during our two-years experience of a new single dedicated to HF outpatient clinic in Salerno, led by cardiologists and specialized nurses. Methods: All data regarding clinical and anthropometric characteristics, used medications and NHYA functional class, number and cause of hospitalizations, deaths and abandonment of a follow-up performed from january 2009 to december 2010 were reported. Patients who left the follow-up we have recalled to administer them a five-items questionnaire regarding reasons of abandonment and degree of satisfaction for cares received.

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S332 Results: 144 patients aged 67.05±11 years, 75% male we studied. Of these, 42% were in NHYA functional class III-IV at time of enrolment. Etiology was: 56% coronary artery disease, 23% hypertension, 10.4% valvular and 10.4% idiopathic. In a mean follow-up of 8.1 months, mean visit number was 3.9. Seventeen patients (5.9% for year) are died. Twenty-five patients (17%) abandoned follow-up. Most of these left the follow-up soon after enrolment. Indeed, this phenomenon has been accentuated in the first 8 month of follow-up. On addiction, abandonment was related to male sex (p = 0.031) but not to others anthropometric and clinical features (age, NHYA functional class, etiology, medications employed). Recalled patients declared their abandonment to be because of poor satisfaction for care or choice of other cares. Nevertheless, the most of these patients think that the follow-up has been beneficial for their health, and declared their availability to come back in our center, if called. But we were not able to find out more than a half of patients lost. On the other hand, proportion of patients with low functional class (NHYA I-II) significantly increased from 58 to 70% during this period. Moreover, number of all causes hospitalizations/patient/year decreased from 1.43 before enrolment to 0.89 during follow-up. Similarly, cardiac cause and HF acute decompensation related hospitalizations respectively decreased from 1.20 to 0.70 and from 0.74 to 0.52 (p \ 0.001). Discussion: During a two-years follow-up in a single dedicated to HF outpatient clinic, our patients experience sensitive improvement in clinic functional parameters, in frequency of acute decompensations and need of in hospital admission. Nevertheless a too high percentage of these patients has abandonned the follow-up. This Phenomenon was more accentuated in male sex and characterized the first months, but perhaps could be mitigated through a more efficient organization of our centre and/or involvement of other territorial institutions, in order to improve satisfaction degree and communication tools with our patients. Conclusions: Need a more structured and comprehensive strategy in order to improve loyalty of our patients, and consequently clinical outcomes. References 1. ESC Guidelines. Eur Heart J 2008;29:2388–442 2. Progr Cardiovasc Nusr 2000;15:97–103 3. Eur J Heart Fail 2005;7:5–17

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 After cardioversion, all pts were divided into 2 groups: a) 25 pts in sinus rhythm (SR), b) 8 pts with permanent AF (pAF). No significative difference was found in hs-CRP levels between the groups (Table 1).

hs- CRP

SR 25 pts

pAF 8 pts

P

3.5 ± 3.8 mg/L

3.1 ± 2.9 mg/L

0.779

In addition to antiarrhythmic therapy, fifteen pts/25 were treated after cardioversion with omega-3 fatty acids, 1 g daily, (Omega3+) by their private physicians. In this subgroup, only 1/15 had permanent AF, while, in the remaining 10 pts (Omega3-), 7 experienced permanent AF. Follow-up 10 months (Table 2).

Omega3+ (15 pts)

Omega3- (10 pts)

P

hs- CRP

1.31 ± 1. mg/L

3.8 ± 2.5 mg/L

0.017

AF+

1

7

0.05

Our pool of pts is too small to consent us any sure conclusion. According to this modest experience, omega-3 fatty acids can maintain sinus rhythm in a majority of non-valvular pts with previous persistent AF, and after 10 months of this treatment hs-CRP values diminished, but it is uncertain if this may be the only explanation. Perhaps, their action may be also due to an enforcement of cellular membranes resistance.

Usefulness of contrast-enhanced ultrasound in the detection of unstable carotid plaque R. Ignarra, C. Acampora, R. Mazzeo, C. Muzj, A. Pinto, L. Romano A.O.R.N. ‘‘A. Cardarelli’’, Napoli, Italy

hs-C reactive protein levels in patients with atrial fibrillation: any chance for omega-3 fatty acids? G. Iannucci1, P. Franciosa2, A. Ciccaglioni2, G. Boccacci1, F. Marolda1, G. Baciarello2 1

Dipartimento di Medicina Interna e Specialita` Mediche; Dipartimento di Scienze Cardiovascolari, Respiratorie, Nefrologiche, Geriatriche, Universita` Sapienza, Roma, Italy

2

Inflammation has been recently associated with atrial fibrillation (AF) and hs- C reactive protein (hs-CRP) has been identified as a marker of unsuccessful attempts of cardioversion, according to some authors. Our group proposed since 2002 the use of omega-3 fatty acids to maintain sinus rhythm in AF patients (pts). Aim of the present study was to evaluate if those acids might influence the evenience of a successful cardioversion, also considering the hs-CRP levels before the procedure. Thirty-three non valvular patients were enrolled, age 69 ± 9 years, 23 men, with persistent AF but no experience of previous perycarditis, tyreotossicosis, or other known inflammatory diseases. Each pt underwent standard ECG, hs-CRP dosage, TEE and then electrical cardioversion by means of biphasic wave, on the same day.

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Purpose: Cerebrovascular diseases (e.g stroke, transient ischemic attack) are one of the most frequent public health problem and these pathological disorders are a major cause of death and disability. These situations can be determined by an embolus detached from an unstable plaque of the carotid artery. Therefore, it is very important to identify early the unstable plaque in the carotid artery and establish an appropriate treatment to reduce the incidence of stroke. Many imaging modalities (e.g MRI, CT, US) were used to try to outline the typical features of carotid artery unstable plaque. Contrast-enhanced ultrasound (CEUS) of carotid arteries allows the direct and real-time visualization of the neovascularization of carotid artery plaque and of the presence of the adventitial network of vasa vasorum. Indeed, it permits a better assessment of the presence luminal irregularities (e.g atherosclerotic ulcers) and a better resolution of the intima-media complex thickness (c-IMT). The aim of our study is to demonstrate the usefulness of contrast-enhanced ultrasound of carotid artery in the detection of unstable plaque in the carotid artery. Contrast-enhanced ultrasound allows to identify sonographic features of unstable plaque in order to distinguish the unstable plaques (which causes the clinical event, in the carotid artery ipsilateral to the cerebral lesion) from the stable plaques (clinically silent, in the carotid artery contralateral to cerebral lesion).

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Materials and Methods: We reviewed carotid artery B-mode ultrasound, color Doppler ultrasound and pulsed Doppler spectral analysis examinations and contrast-enhanced ultrasound of 20 patients with recent ischemic stroke, patients with transient ischemic attack, amaurosis fugax, carotid artery bruit. Inclusion criteria were at least one carotid artery atherosclerotic plaque thicker than 2.0 mm. All patients underwent CT and/or MRI of the brain. The area and the side of the affected cerebral hemisphere on CT and/or MRI images are defined. Patients who presented with hemorrhagic stroke on CT and/ or MRI images were excluded. Ultrasound examinations were performed using an ultrasound machine equipped with a 7-L linear probe (frequency: 6-9 MHz). Results: In all 20 patients, the neovascularization of carotid artery plaque was most prominent in the same side of the cerebral hemisphere affected by ischemic brain injury on CT images, compared to contralateral brain. The administration of ultrasound contrast medium allowed us to better assess the neovascularization of carotid artery plaque, the presence of parietal irregularities (e.g atherosclerotic ulcers), the adventitial network of vasa vasorum and the c-IMT of the carotid artery wall. Discussion: Cerebrovascular disease is one of the leading causes of death and morbidity. The carotid artery plaques are frequent in stroke patients and the presence of carotid artery plaques is correlated with an increased risk of stroke. Therefore, it is important to use a noninvasive imaging method to identify in particular the presence of unstable (‘‘vulnerable’’) plaques, which are more probably subject to rupture. Ultrasonography is the examination of first instance in patients with carotid artery disease. On B-mode US images, echolucent plaques correspond to histologic features of plaque instability. More echolucent lesions have a higher degree of neovascularization. The use of ultrasound contrast agent allows a better definition of the near wall, which is considered a reliable marker of atherosclerosis. The neovascularization of carotid artery plaque may be quantized to identify patients at risk for stroke. After administration of contrast-enhanced ultrasound, the degree of neovascularization in atherosclerotic carotid artery plaques is correlated with the histologic density of neovessels. The ultrasound contrast medium allows the identification of neovascularization associated with atherosclerosis (e.g periadventitial vasa vasorum network and intraplaque neovascularization), which is the most specific marker of unstable carotid artery plaque Contrast-enhanced ultrasonography of the carotid arteries is a promising technique to detect unstable carotid artery plaques, in order to identify patients at risk for cardiovascular disease monitoring their evolution and response to therapy. Conclusion: In conclusion, cerebrovascular diseases (e.g stroke, transient ischemic attack) are a major cause of death and disability. The presence of intraplaque neovascularization and hyperplastic network of vasa vasorum were considered as predictors of unstable lesions in cerebrovascular and/or cardiovascular patients. Contrast-enhanced carotid ultrasound (CEUS) of carotid arteries allows the identification of a unstable carotid artery plaque and of its neovascularization related to atherosclerosis. Contrast-enhanced carotid ultrasound also allows a better sonographic definition of the carotid artery plaque, particularly of parietal irregularities, such as ulcers and it improves the sonographic resolution of the arterial walls with a more detailed study of intima-media complex thickness, especially at the near wall. in order to establish an appropriate treatment to reduce the incidence of stroke. Prevalence of pro-thrombotic genetic polymorphisms in infective endocarditis D. Iossa, R. Molaro, R. Casillo, C. Caianiello, I. Mattucci, D. Pinto, F. Agrusta, U. Malgeri, R. Andini, A. Senese, R. Albisinni, E. Ragone, R. Utili, E. Durante-Mangoni Cattedra di Medicina Interna, II Universita` di Napoli, AO Monaldi, Napoli, Italy

S333 Background: The pathogenesis of infective endocarditis (IE) comprises a two-step process: the initial formation of a non-bacterial clot is followed by bacterial seeding on the clot during bacteremia. The risk factors for non-bacterial clot formation are unknown. Inherited thrombophilias are common causes of thrombosis and may be overrepresented in heart disease patients. However, no study has evaluated the potential role of the major inherited thrombophilias in the pathogenesis of IE. Objective: To assess the prevalence and clinical significance of three major genetic polymorphisms associated with thrombophilia in patients with infective endocarditis (IE). Methods: We studied 157 Caucasian patients admitted to our centre because of definite IE. As controls, we studied 125 Caucasian blood donors from the same geographical area. All patients underwent blood cultures and echocardiography ([90% transesophageal). Genomic DNA was extracted with a spin-column method and subjected to PCR–RFLP analysis to seek for the following polymorphisms: factor V G1691A (FV Leiden), prothrombin 3’UTR G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T. Results: Patient median age was 60 years (17-87), 73% were males. 108 (69%) had left- and 49 (31%) right-sided IE. 97% of patients showed intracardiac vegetations with a median length of 14 mm. Blood cultures grew gram-positive cocci in most cases. The allelic frequencies in IE patients and controls were as follows: FV Leiden 4% vs 0% (p = 0.063); prothrombin 2.8% vs 2% (p = 0.96); MTHFR 43% vs 31% (p = 0.05). Prevalences did not significantly differ according to the heart side involved (left, arterial flow vs right, venous flow) or type of IE (valvular vs device). Overall, the prevalence of these inherited thrombophilias was neither higher in patients with stroke or embolic complications nor in those carrying larger vegetations. Conclusion: Our preliminary data seem to suggest that IE patients could be more likely than healthy controls to carry genetic polymorphisms associated to thrombophilia. Whether these inherited factors play a pathogenic role in the initiation and progression of IE remains unclear and warrants further study.

FGF-23 As a new marker of subclinical atherosclerosis in ra patients A. Koverech, L. Ferri, A. Negro, A. Biscotti D’agostino, A. Sebastianelli, E. Alessi, M. Iannotta, M. Trappolini, M. Proietta, F. Del Porto Universita` ‘‘Sapienza’’ Roma, Ospedale Sant’Andrea, II Facolta` di Medicina e Psicologia, Dipartimento di Scienze Cliniche e Molecolari, Roma, Italy Background: Atherosclerosis (ATS) is a multifactorial disease in which genetic, environmental and immune factors trigger and maintain inflammation inside the arterial wall. It is well known that in patients with active rheumatoid arthritis (RA) cytokine release and inflammation are early and represent the predisposing substrate accelerating ATS, so that RA is considered an additional risk factor for ATS. Moreover in RA patients increased values of common carotid artery intima-media thickness (cIMT), an ultrasonographic marker of subclinical ATS, have been observed, primarily related to the disease duration and inflammation. Recently it has been suggested that some mediators of bone metabolism are involved in the pathogenesis of ATS. In particular high phosphorus and parathormone (PTH) values as well as low vitamine D3 levels have been associated with increased cardiovascular risk. Among regulatory mediators of calcium/phosphorus metabolism, fibroblast growth factor (FGF)-23, which exerts phosphaturic actions also by inhibiting vitamin D hydroxylation, has been associated with cardiovascular events both in patients with impaired renal function and in those with normal renal

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S334 function. The aim of this study was therefore to evaluate i) FGF-23 levels in 20 patients with RA (Group RA) ii) FGF levels in the same 20 RA patients divided into two groups on the basis of carotid ultrasound: patients with evidence of atherosclerotic plaque (group A) and patients without evidence of atherosclerotic plaque (group B) iii) whether FGF-23 levels are related to carotid athrosclerosis in RA patients. Patients and Methods: Twenty consecutive RA patients newly diagnosed on the basis of the ACR criteria have been selected among those attending to our outpatient clinic; 20 healthy subjects matched for age and sex have been used as control group (Controls). Only in RA patients disease activity score (DAS) was calculated on the basis of ACR criteria. Each patient and control was evaluated for the presence of traditional cardiovascular risk factors such as diabetes mellitus, blood pressure, total cholesterol (t-chol), HDL-cholesterol (HDL), LDL-cholesterol (LDL) and triglycerides (Try), cigarette smoking and BMI. C-reactive protein (C-RP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), anti-cyclic citrullinated peptide (aCCP), calcium (Ca), phosphorus (P), PTH, calciuria, phosphaturia, D3 vitamin and FGF-23 levels were also assessed. Moreover in all patients and cIMT was evaluated by ultrasound. On the basis of carotid ultrasound the RA group was divided in two subgroup: with evidence of carotid ATS (group A) and without evidence of carotid ATS (group B). Statistics: results have been expressed as mean ± standard deviation. T-student test has been used to perform statistic analysis. P \ 0.005 has been considered significant. Results: Results obtained from the comparison between group RA and controls showed in the group RA a significant increase of both right and left IMT (p [ 0.001 both RcIMT and LcIMT), ESR (p \ 0.0001), C-RP (p \ 0.0001) and FGF-23 levels (p \ 0.002), whereas no significant differences were observed in the other parameters under evaluation. Results obtained from the comparison between group A and B showed in group A significant increase of t-chol, LDL values (p 0.028 and p 0.047 respectively) and fibrinogen (p \ 0.001) levels. Moreover in group A a significant raise of DAS (p \ 0.007), ESR (p 0.019), C-RP (0.014) and FGF-23 levels were documented, whereas no significant differences were observed regarding the other parameters under evaluation. Conclusions: Result of our study confirm that RA represent an additional risk factor for carotid atherosclerosis both by inflammatory pathways and by worsening traditional cardiovascular risk factors. Moreover our results suggest that FGF-23 may be considered a marker of subclinical carotid atherosclerosis in RA patients.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 accounting for 0.7%-2.6% of all ICU admissions for acute coronary syndrome. Its pathophysiology is frequently related to psycho-physical acute stress, but epicardial multivessel coronary damage, alterations of the coronary microvessels, neurogenic stunning, catecholaminergic cardiotoxicity are believed to play an etiologic role. Excessive response of the adrenoreceptors is thought to be the responsible for heart dysfunction. Indeed, increase in serum catecholamines and highest sympathetic innervation density of the heart apical region has been documented by some studies. Risk factors such as diabetes and hypertension are not higher than those found in the general population. Unlike the acute coronary syndrome, the symptoms of the Takotsubo cardiomyopathy were lasting from 6 a.m to 6 p.m. The therapy of this syndrome consists in treating its complications like heart failure and cardiogenic shock. Anticoagulants and anti-ischemic therapy is also indicated.

Fig. 1 EKG of an Takotsubo cardiomyopathic patient

A cardiologic emergency I. Kushta, S. Lucci, S. Lucia, M. Muscaritoli, F. Rossi Fanelli Department of Clinical Medicine, Sapienza University, Rome, Italy Case report: A 56-year-old woman was admitted to our ICU for the suspection of endocranial hemorrhage. A CT scan was performed and found no parenchymal alterations nor endocranial hemorrhage. During the stay at the ICU the patient complained of chest pain with back irradiation. An EKG was perform showing an ST elevation in SII, V2V6 and T inversion. An aortic angiography was performed, given the back irradiation, to exclude aortic dissection, but no flapping or fake lumen was observed. The patient was then underwent coronary angiography. Coronary arteries were normal. A ventriculography was then performed showing an apical discinesia and a basal hypercynesia. The picture was suggestive of Takotsubo cardiomyopathy. Discussion: Takotsubo cardiomyopathy is a rare (incidence 6%, female: male ratio of 6-12:1) and usually reversible syndrome characterized by acute regional systolic dysfunction of the left ventricle,

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Fig. 2 Ventricolography of an Takotsubo cardiomyopathic patient showing the typical ‘‘takotsubo’’ shape

Effect of acute lung exposure to carbon nanotubes on the cardiac autonomic regulation: experimental studies in conscious rats. J.M. Legramante*, S. Sacco*, P. Crobeddu*, A. Pietroiusti*, A. Magrini*, F. Valentini*, G. Palleschi*, G. Galante, G. Raimondi** *Tor Vergata, Univerita` di Roma; ** Sapienza, Universita` di Roma, Roma, Italy

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 There is strong evidence that episodic high levels of airborne particulate matter (PM) are associated with stroke, heart attacks, heart arrhythmias, and sudden death; these events may be precipitated, at least in part, by alterations in the autonomic input to the heart, which can be displayed by a partial or total loss in spontaneous heart rate variability (HRV). Indeed, decreased HRV is highly predictive for increased risk of arrythmias and sudden cardiac death, especially in subjects with ischemic heart disease. Aim of the study was to test the hypothesis that single wall carbon nanotubes (SWCNT) pulmonary exposure acutely affect the autonomic cardiovascular regulation in conscious rats. Materials and methods: We studied 16 Wystar-Kyoto rats in which a telemetry transmitter for continuous AP and HR recordings was surgically implanted. SWCNT dispersed in phosphate buffer saline (PBS) or PBS alone were randomly administered intratracheally. Immediately before, and 24 h after each instillation a 10 min AP recording was performed. The sequence analysis was performed to evaluate the baroreflex function. Rats were randomly divided into two groups: control rats (n = 7) and SWCNT instilled rats (n = 9). Results: In the control group PBS instillation did not induce any significant changes in the occurrence (8.3 ± 0.68% vs 8.1 ± 0.34% for baroreflex and 4.1 ± 0.51% vs 4.5 ± 1.0% for nonbaroreflex) and in the sensitivity (4.1 ± 0.96 vs 6.1 ± 2.06 ms/mmHg for baroreflex and 4.1 ± 0.95 vs 5.2 ± 1.44 ms/mmHg for nonbaroreflex) both of baroreflex and nonbaroreflex sequences. At variance the SWCNT exposure induced a significant reduction of BRS (3.5 ± 0.6 vs 2.6 ± 0.40 ms/mmHg) and of the sensitivity of nonbaroreflex sequences (3.4 ± 0.48 vs 2.7 ± 0.31 ms/mmHg) without significant changes in the occurrence of both baroreflex (7.5 ± 0.47% vs 7.4 ± 0.38%) and nonbaroreflex sequences (3.9 ± 0.24% vs 4.2 ± 0.38%). These data might suggest that the autonomic cardiovascular regulation is affected by acute SWCNT exposure by acting both on the negative feedback mechanisms of baroreflex origin and mainly vagally mediated and on the feedforward mechanisms more likely mediated by the sympathetic nervous system Our results show that SWCNT pulmonary exposure might affect the cardiovascular autonomic regulation thus contributing to cardiac and arrhythmic events. In conclusion the results of the present study show that SWCNT pulmonary exposure might affect also the cardiovascular system and in particular the acute exposure to nanomaterials might alter the physiological autonomic regulation thus contributing to cardiac and arrhythmic events as reported in response to PM and UF particles exposure.

Plasma levels of matrix metalloproteinases and their inhibitors in hypertension: a systematic review and meta-analysis C. Marchesi1, F. Dentali1, E. Nicolini1, A.M. Maresca1, M.H. Tayebjee2,5, M. Franz3, L. Guasti1, A. Venco1, E.L. Schiffrin4, G.Y.H. Lip5, A.M. Grandi1 1 Department of Clinical Medicine, University of Insubria, Varese, Italy; 2Department of Cardiology, Leeds Teaching Hospitals NHS Trust, UK; 3University Hospital Jena, Germany; 4Department of Clinical Medicine, SMBD-JGH, McGill University, Montreal, Canada; 5University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK

Background: The remodeling of the extracellular matrix is controlled by the matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs). Hypertension is a major cause of cardiovascular (CV) remodeling. The aim of this meta-analysis is to elucidate the behaviour of plasma MMP and TIMP levels in hypertension and their relationship to CV remodeling.

S335 Methods: MEDLINE and EMBASE databases were searched up to June 2010. Studies were considered eligible if they provided values of plasma MMPs and TIMPs in hypertensive subjects. Given the high variability of the plasma biomarker values among studies, the standardized mean difference (SMD) was calculated. Results: Thirteen studies provided data of plasma TIMP-1 and three of TIMP-2. For plasma TIMP-1, the SMD between 901 hypertensives and 395 normotensives was 1.36 units (95% CI 0.41-2.31, P \ 0.01). For TIMP-2, the SMD between 274 hypertensives and 165 normotensives was 0.3 units (95% CI 0.1-0.51, P \ 0.01). The heterogeneity was high for TIMP-1 and low for TIMP-2. Three studies investigated whether plasma TIMP-1 predicted left ventricular (LV) remodeling: the SMD between 92 hypertensives with and 88 hypertensives without LV hypertrophy was 5.81 units (95% CI 0.92-10.69, P \ 0.05). The heterogeneity was high. Differences in plasma MMP-1, -2 or -9 between hypertensives and normotensives were not significant. Conclusions: These results suggest that whereas MMPs do not appear to be biomarkers of hypertension and cardiac hypertrophy, plasma TIMPs are. If these results are confirmed in prospective clinical studies, they could provide new tools to stratify CV risk in hypertensive patients.

Homocysteine blood level association with cerebrovascular events S. Mazzuca, S. Giancotti, C. Pintaudi, G. Muccari, V. Nestico`, M.T. Polistena, R. Cimino S. O. C. Internal Medicine, Az. Osp Pugliese, Ciaccio, Catanzaro, Italy Background: Recently in scientific literature the role of homocysteine (Hcy) in cerebrovascular events has been widely discussed. It has been found that hyper-homocysteinemia is directly toxic to endothelium as it activates the growth of smooth muscle cells in vascular wall and suppresses the development of endothelial cells contributing to endothelial dysfunction. Objectives: We estimated the relationship between hyper-homocysteinemia and acute cerebrovascular events and we investigated if Hcy was an independent and serious risk factor for stroke in patients hospitalized in our division Methods: We recluted 61 non diabetic consecutive patients with TIA or stroke hospitalized in our division in 2010. In all patients (22 female and 39 male, mean age 57,2 ± 12,8) were determined plasma Hcy level. In all patients national institute health stroke scale (NIHSS) was calculated for estimated the neurological deficit. The patients’ assessment included clinical examination, systolic blood pressure, Ankle-Brachial Index, Body mass index, total cholesterol, LDL Cholesterol, HDL cholesterol, PCR, microalbuminuria, creatininemia. The patients were also submitted to a tomography or magnetic resonance of brain and CCA-IMT was used as an indicator of atherosclerotic process, Information on mortality and residual disability following cerebrovascular events is based on information on the clinical outcome collected at discharge from the hospital and after follow-up visits that were performed at 3 and 6 months. Multiple regression analysis was used for statistical elaboration. Results: After the follow-ups at 6 month 9 patients (14,7%) died during the acute phase (Group A),of note 6 deaths were caused by an underlying condition (cancer), 7 patients (11,4%) were moderately or severely impaired at the end of follow-up (Group B), 45 patients (73,9%) had a complete recovery (Group L). Comparing 16 patients (Group A +B)) vs 45 patients (Group L) we revealed: systolic blood pressure 155.8 ± 20.1 mmHg (A + B)) vs 123.3 ± 20.4 (L) p \ 0,32; Body mass index 25.2 ± 3.3 (A) vs 23.4 ± 2.6 (U) pNS; Age 59.6 ± 6.5 (A + B) vs 51.8 ± 4.9 years (L) p \ 0,001; male sex: 12 vs 4 female sex (A + B), p\0,05; total cholesterol 233±28 (A+B) vs190±30 mg/dl (L)\p0,32; LDL Cholesterol 130 ± 30 (A + B) vs 129 ± 31 (U) pNS;

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S336 HDL cholesterol 39 ± 14 (Group A + B) vs 43 ± 15 (L) p 0,32. It was found that 16 patients (Group A + B) had 28,5% higher plasma Hcy level than patients (Group L): 19,4 ± 3,7 vs 8,01 ± 2,6 mcmol/l respectively. Serum Hcy level was associated with progression of disease (r = 0,32), patients’ functional status (r = 0,37),degree of vessel involvement (r = 0,46). After adjustment for age and sex, at the regression analysis a direct correlation was observed between Hcy and national institute health stroke scale (p \ 0,05). Conclusion: Hyper-homocysteinemia in an independent risk factor for cerebrovascular events and it is associated with an increased death during acute phase of stroke.

Urinary sepsis with fever in a patient with a family history of polycystic kidney and liver disease, arterial hypertension, ischemic encephalopathy and chronic renal insufficiency G. Meduri1, C. Carery1, A. Caserta1, A. Scordo1, F. Demetrio1, P. Lipari1, I. Tarzia1, A. Nucera1, A. Stellitano2, E. Stellitano1 Ospedale Tiberio Evoli, Melito Porto Salvo ASP 5 RC; 2Dipartimento Medicina Interna, AOU Policlinico G. Martino, Messina, Italy 1

Anamnesis : S.T.Age: 63 years old; Sex: female Father died, affected by polycystic kidney disease. Blood paternal uncle with polycystic kidney disease. 29-year-old daughter with polycystic kidney disease. In 1996 diagnosis of polycystic kidney disease. Arterial hypertension. In 2010 total right mastectomy for infiltrating ductal carcinoma. For about 3 years chronic renal insufficiency. For a few days fever, shivering, pain in the right lumbar region. E.O. pale pink skin and mucous membranes, not swollen lymph nodes, results following left mastectomy. Torax: negative Heart: Rs 70b/m (Sinus rythm: 70 beats per minute) visible but not palpable itto. Abdomen: globular and tractable. Manouvre of Giordano: positive on the left side ++-. E.O. Neurologic examination: normal T 39 PA 140/80 Ematochimic examinations: G.B. 16,39 9 10^3/ll; N 84,6% L 7,1% G.R.4,630 9 10^6/ll HB 14,3 g/dl,PLT 183 9 10^3/ll. Urea test, creatinin test, potassium test, calcium test, PCR test, Uric acid test, rheuma test Lab tests: Urine culture test, positive for Escherichia Coli strain. Instrumental examinations: ECT abdomen: Liver imaging shows numerous cyst-like areas. In the bilateral renal loggia there are numerous anechoic areas expression of polycystic backs. RX Torax: negative ECG: Sinus rhythm 80 beats per minute. BBdx Conclusion: in accordance with the recent international literature the clinical case shows the genetic factors in the etiopathogenesis of polycystic kidney disease as well as the implications of arterial hypertension in particular and the high risk of cardiovascular implications in general.

Serum paraoxonase (pon1) activities are reduced in metabolic syndrome and may modulate the related risk of coronary artery disease R. Micaglio1, N. Martinelli1, D. Girelli1, P. Guarini1, L. Consoli1, E. Grison1, S. Friso1, F. Pizzolo1, E. Trabetti2, P.F. Pignatti2, R. Corrocher1, O. Olivieri1 Department of Medicine, University of Verona, Italy; 2Department of Sciences of Life and Reproduction, University of Verona, Verona, Italy

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Background: Oxidative stress is thought to play a pivotal role in metabolic syndrome (MS). Low levels of high-density lipoprotein (HDL) are one of the most characteristic element in the cluster of MS. The antioxidant ability of HDLs is in part attributable to serum paraoxonase (PON1). Methods: PON1 activity versus different substrates, i.e. paraoxon, phenylacetate, 5-thiobutyl butyrolactone (TBBL) and 7-O-diethyl phosphoryl 3-cyano 4-methyl 7-hydroxycoumarin (DEPCyMC), have been analyzed in 293 subjects with or without MS clinical definition and with or without angiographically proven coronary artery disease (CAD). Results: All PON1 activities were lower in MS and there was a significant decreasing trend of PON1 activities by increasing the number of MS abnormalities. The strongest association was found for DEPCyMCase activity, which is considered a surrogate marker of PON1 concentration (20.60 ± 6.05 in MS vs. 23.8±5.6 mU/ml in noMS, P = 1.58 9 10-5). Such association was independent from HDL and apolipoprotein A-I levels. Interestingly, subjects with low HDL levels but without MS had a higher DEPCyMCase activity than subjects with equally low HDL levels and with MS, and similar with that of subjects with high HDL levels and without MS. On the other hand subjects with high HDL levels but with MS tended to have a lower DEPCyMCase activity. Finally, in a adjusted regression model subjects with MS and concomitant low levels of DEPCyMCase activity – the lowest tertile – presented a marked increase of CAD risk (OR 4.34 with 95%CI 1.44-13.1), while subjects with MS but with an high DEPCyMCase activity—the highest tertile—did not present a significant increase of CAD risk (OR 1.45 with 95%CI 0.47-4.46). Conclusions: our results suggest that low PON1 concentrations are characteristic in MS and may modulate the MS-related CAD risk.

Cardiovascular remodeling in patients with abdominal adiposity: correlation with central arterial blood pressure and aortic stiffness C. Mongiardi, A.M. Maresca, C. Marchesi, L. Merletti, F. Annoni, V. Vacirca, E. Nicolini, A. Bertolini, A.M. Grandi, A. Venco Department of Clinical Medicine, University of Insubria, Varese, Italy Background: Previous studies demonstrated that obesity is associated with cardiovascular (CV) remodeling. Little evidence is available regarding the relation between central arterial blood pressure (BP) and cardiovascular remodeling in patients with abdominal obesity. The aim of the study was to evaluate the correlation between left ventricle (LV) morpho-functional characteristics, carotid intimamedia thickness (IMT), central arterial BP and aortic stiffness in overweight/obese patients. Methods: We consecutively enrolled 54 patients without active smoke, CV disease and diabetes, never treated with-anti hypertensive drugs or statins. Among them: 34 patients showed body mass index (BMI) C25 kg/m2 and abdominal circumference (AC) [102 cm for men and[88 for women; 20 patients showed BMI\25 kg/m2 and AC \102 cm for men and \88 for women (BMI: 30.2 ± 3.7 vs. 22.7 ± 1.2 kg/m2, P \ 0.001; AC: 103.6 ± 8.9 vs 86 ± 4.6 cm, P \ 0.001). Each patient underwent: ambulatory 24 h BP monitoring, echocardiographic examination, carotid ultrasonography, tonometry and measurement of the carotid-femoral pulse wave velocity (PWV). Results: The two groups did not differ for age (46 ± 6 vs. 45 ± 7 years, ns), sex, systolic and diastolic 24 h BP. Serum PCR values were higher in the overweight/obese group (3 ± 2.3 vs. 1.2 ± 0.9 mg/dL, P \ 0.001). LV mass index was higher in the

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 overweight/obese group (37.7 ± 7.3 vs. 31.2 ± 6.8 g/h2.7, P \ 0.006). There was no significant difference between the two groups regarding relative wall thickness, end-diastolic LV diameter and ejection fraction. As for diastolic function, the overweight/obese group showed lower E’/A’ ratio (interventricular septum, Tissue Doppler Imaging, TDI) (0.72 ± 0.2 vs. 0.91 ± 0.31, P \ 0.04), higher E/E’ ratio (7.5 ± 1.6 vs. 5.9 ± 1, P \ 0.001) and E/Em ratio (lateral wall, TDI) (4.90 ± 0.91 vs. 4 ± 0.8, P \ 0.003). Carotid IMT was greater in the overweight/obese group (0.74 ± 0.13 vs. 0.66 ± 0.16 mm, P \ 0.05). There was no difference in the carotid-femoral PWV between the two groups (7.3 ± 2.7 vs. 6.5 ± 1.15 m/s, ns). The systolic aortic BP was higher (124 ± 12 vs. 110 ± 1.10 mmHg, P \ 0.001) in the overweight/obese group. There was a positive correlation between the aortic central BP and the PWV with the LV mass (r = 0.306, P = 0.02, r = 0.49 P = 0.001) and the carotid IMT (r = 0.271, P \ 0.04, r = 0.457, P \ 0.001). Conclusions: In overweight/obese patients with abdominal obesity, CV remodeling appear to be significantly influenced by central BP and arterial stiffness.

Early increase in renal resistive index in hypertensive patients with diabetes mellitus and normal arterial stiffness G. Pacciani, V. Maestripieri, N. Zaffarana, I. Tassinari, M.C. Cavallini, A. Berni, E. Ciani, M. Bernetti, R. Abbate, L. Poggesi, M. Boddi Dipartimento di Area Critica Medico-Chirurgica, Universita` di Firenze, AOU Careggi, Firenze, Italy Background: Renal resistive index (RRI) detected by Doppler ultrasound is influenced by intra- and extra-renal factors. Increased RRI in patients with normal renal function detects tubulo-interstitial damage, which may be present before glomerular damage. Arterial wall stiffness evaluated by estimation of pulse wave velocity (PWV) is one of the most significant extra-renal factors. Both RRI and PWV are significantly higher in patients with hypertension and diabetes mellitus (DM) than in age-matched control subjects. However, the role of intra- and extra-renal factors in determining the RRI increase is still under debate. This study was aimed to evaluate whether high RRI values of patients with hypertension and DM reflect tubulo-interstitial damage or increased arterial stiffness. Methods: We studied hypertensive patients between 45 and 75 years, in chronic antihypertensive therapy, with or without DM, with conserved renal function (creatinine clearance [60 mL/min). RRI [(peak systolic velocity – end-diastolic velocity]/peak systolic velocity) was calculated by the analysis of the Doppler flow wave obtained at the renal interlobar arteries and considered pathologic when C0.70 or [95% of upper confidence limit expected for age decade. Results: We evaluated 21 patients (58 ± 8 years, 15 M/6F). Ten were affected by DM. Patients with DM were older (62 ± 8 vs. 54 ± 4 years, P=0.01) and had significantly higher RRI values (0.69 ± 0.05 vs. 0.65 ± 0.07, P \ 0.05) and prevalence of pathologic RRI (6/10 vs. 2/11, P \ 0.05), compared to patients without DM. There was no significant difference in PWV values between hypertensive patients with or without DM (approximately 8 m/sec). DM resulted a significant independent predictor for pathologic RRI (crude O.R. 6.8; CI 95% 1.2-49.2; P \ 0.05), even after adjustment for age (O.R. 8.1; CI 95% 1.1-85.8, P \ 0.05) and PWV (O.R. 5.1; CI 95% 1.1-40.0; P \ 0.05). Conclusions: In our hypertensive patients with DM, increased RRI values may reflect a reduction in intra-renal compliance due to tubulointerstitial damage, rather than an increase in systemic arterial stiffness.

S337 Angiogenic, Arteriogenic, and Vasculogenic properties of SHH M. Palladino***, I. Gatto*, V. Neri***, M. Silver**, S. Straino***, R.C. Smith**, F. Crea****, A. Tritarelli****, E. Gaetani*, M. Capogrossi***, R. Pola*** *Medicine Dept, A. Gemelli University Hospital, Rome, Italy; **Medicine Dept, St Elizabeth’s Medical Center, Boston, MA; ***Vascular Pathology, IDI, Rome, Italy; ****Cardiovascular Medicine Dept, A. Gemelli University Hospital, Rome, Italy Background: Sonic hedgehog (Shh) is a morphogen regulating epithelial-mesenchymal interactions during embryogenesis. In post-natal life, Shh is a potent indirect angiogenic agent, able to upregulate different families of angiogenic growth factors. Furthermore, Shh gene transfer enhances the contribution of bone marrow (BM)-derived endothelial progenitor cells to myocardial neovascularization. Aim of the Study: In this study, we tested the beneficial potentials of Shh gene therapy in an experimental model of peripheral limb ischemia. Methods: Unilateral hindlimb ischemia was induced in 1-year-old C57BL/6J mice, by excising the femoral artery, from its proximal origin as a branch of the external iliac artery till the bifurcation into saphenous and popliteal arteries. Immediately after induction of ischemia, some mice were treated with a plasmid encoding the human Shh gene (phShh), while other mice were treated with the empty plasmid and used as controls. The phShh gene (or the empty plasmid) was administered by intramuscular injection, at the dose of 200 lg, directly into the ischemic hindlimb. Blood flow was measured in ischemic and contralateral hindlimbs by laser Doppler perfusion imaging at days 0, 7, 14, 21, and 28 after ischemia. At day 28, mice were sacrificed and adductor muscles were analyzed for capillary and arteriole density. An additional set of 1-year-old C57BL/6J mice were used to study the effects of phShh therapy on the mobilization of bone marrow (BM)-derived endothelial progenitors in the course of ischemia. Mice were underwent hindlimb ischemia as described above and then received treatment with 200 lg of phShh or empty plasmid. Mice were sacrificed at day 2, 4, and 7 after induction of ischemia and peripheral blood samples were obtained. FACS analyses were used to detect CD45-/ Sca-1+/Flk-1+ cells. We also used a BM transplantation model to test the effects of phShh gene therapy on the homing of BM-derived endothelial progenitor cells in the setting of hindlimb ischemia. We also measured local expression levels of VEGF165, Ang-1, and SDF-1a s in mice treated with 200 lg phShh or empty plasmid 7 days after ischemia, to determine if Shh treatment increases the expression of these prototypical angiogenic, arteriogenic, and vasculogenic agents. Results: At day 28 after ischemia, blood perfusion ratio between the ischemic and the contralateral leg was 0.97 ± 0.01 in Shh-treated mice and 0.68 ± 0.03 in control animals (p = 0.008). Capillary and arteriole density were significantly higher in the phShh-treated muscles compared to controls (p = 0.02; p = 0.03, respectively). Treatment with phShh also significant increased the number of circulating CD45-/Sca-1+/Flk-1+ cells, compared to control (p \ 0.05). In the BM transplantation model, the number of progenitor cells derived from the BM that had incorporated into new vessels in the setting of the ischemic hindlimb was significantly higher in phShhtreated animals than in empty plasmid-treated mice (p = 0.000002). Finally, the expression levels of VEGF165, Ang-1, and SDF-1a was significantly higher in animals treated with phShh than in mice treated with control (p = 0.00001; p = 0.00054; p = 0.00003, respectively). Conclusions: The current standard of care for ischemic diseases relies on direct revascularization, either by endovascular techniques or open surgical approaches. Early preclinical studies and phase I clinical trials achieved promising results with growth factors administered as recombinant proteins or single-agent gene therapies. In this study, we show that a plasmid containing the human Shh gene induces simultaneous activation of angiogenic, arteriogenic, and vasculogenic mechanisms, with beneficial effects in a model of peripheral artery disease.

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S338 Evaluation of vascular homeostasis and inflammation markers in HIV-1 infected patients on effective haart after 3 months from switching to abacavir/lamivudine fixed dose D. Pastori, A. Esposito*, L. Perri, R. Carnevale, S. Di Santo, L. Loffredo, C. Fimiani*, A. Fantauzzi*, R. Cangemi, S. Basili, I. Mezzaroma* Dipartimento di Medicina interna e specialita´ Mediche; *Dipartimento di Medicina clinica, ‘‘Sapienza’’, Universita` di Roma, Roma, Italy Background: Increasing evidences suggest that HIV-1 positive subjects have a significant increased cardiovascular risk. A key role is played by HIV-1 infection itself, immune activation and chronic inflammation. Furthermore, alterations in lipid and glucose metabolism associated with antiretrovirals drugs are described. The DAD Study showed a significant increase of myocardial infarction risk in patients on ABC, characterized by a rapid onset of ischemic damage and not linked to the treatment length. Pathogenetic mechanisms of vascular damages are still unclear. Better understanding of drug actions would allow a more accurate selection of patients to be treated with ABC, as it is usually done with HLA-B5701 screening. Objectives: To determine the role of Abacavir/Lamivudine (ABC/ 3TC) on vascular homeostasis and cardiovascular risk compared to Zidovudine/Lamivudine (ZDV/3TC) or Tenofovir/Emtricitabine (TDF/FTC). Evaluated parameters (baseline and after 3 months): echocardiographic parametres, Ankle-Brachial Index (ABI), IntimaMedia Thickness (IMT), Flow-Mediated Dilation (FMD), Reactive Oxidant Species (ROS), PAC-1, glucose, total cholesterol, LDL and HDL, triglycerides, ESR, CRP, fibrinogen and D-dimers, HLA-DR and CD38 on CD4+ and CD8+ T lymphocyte. Results: 15 patients on TDF/FTC (Group 1) and 15 patients on ZDV/ 3TC (Group 2) were evaluated. 10 per group reached 3 months. At baseline both groups showed no statistically demographic and metabolic differences. Activation and inflammatory markers, oxidative stress and platelet activation were similar. Only CRP showed a significant difference (2810 g/l in Group 1 vs 1190 g/l in Group 2). After 3 months Group 1 showed no differences in all evaluated parameters. In Group 2, ABI had a significant change, rising from values of potential pathological status to normal (right ABI: 1,34±0,12 vs 1,17±0,16 p = 0,002; left ABI: 1,36±0,06 vs 1,10 ± 0,16 p = 0,03). Values of FMD improved in both group although not statistically significantly. All other parameters remained unchanged. Both groups showed an increase in total cholesterol and LDL. No changes in CD4+ T cells occurred, whereas a decrease of activation markers on CD4+ T cells was present in both groups. No echocardiographic abnormalities occurred. Conclusions: These results indicate some preliminary observations. 1) The ABC pro-inflammatory effect seems unconfirmed in the short term. 2) FMD tends to increase after the switch in both groups, suggesting a favourable effect of ABC/3TC on endothelial function; also IMT tends to decrease in both groups, whereas ABI shows a significant improvement after switch in ZDV/3TC patients. The data, needing to be confirmed, indicate a positive effect on vascular homeostasis after switching to ABC/3TC also in subjects previously on TDF/FTC.

Atherosclerosis: what therapy? P. Mario Sergio Department of Internal Medicine and Medical Specialities I University of Rome Sapienza, Rome, Italy Background: Atherosclerosis is the leading cause of death and disability in the developed world. It interests a large and medium-sized

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 muscular arteries and it is characterized by endothelial disfunction, vascular inflammation, piling up of lipids, cholesterol, calcium, and cellular debris into the intima of the vessel wall. The final result is the plaque formation, vascular remodeling, acute and chronic luminal obstruction, abnormalities of blood flow, and diminished oxygen distribution to target organs. Physiopathology: The pathophysiological aspects of this process remain poorly recognized and incompletely understood. Several theories have been proposed and, at the present moment, the ‘‘response-to-injury’’ theory is universally accepted. Vascular inflammation is caused by endothelial injury that in its turn elicits a fibroproliferative response. The most probable causes of the endothelial injury are the oxidized low-density lipoprotein cholesterol (LDL); infectious agents; toxins, e.g. the byproducts of cigarette smoking; hyperglycemia, and hyperhomocysteinemia. Because of the endothelial injury circulating monocytes penetrate through the injured intima of the vessel wall, turning into tissue macrophages that act as scavenger cells, taking up LDL cholesterol and forming the characteristic foam cell, a typical element of early atherosclerotic lesion. Oxidized and small-dense LDLs cause, in various degrees, toxic effects and disfunctions of the endothelial cells tight associated with atherosclerosis. These events led to impaired endothelium-dependent dilation and paradoxical vasoconstriction as a result of direct inactivation of nitric oxide mediated by the excessive production of free radicals, and reduced transcription of nitric oxide synthase messenger RNA. The reduction of nitric oxide determines a thrombophilic state and potentiates the proliferative stage of plaque maturation. Also, the oxidized-LDLs prime inflammatory processes with recruitment of monocytes/macrophages and elicits the production, by vascular wall cells, of chemoattractant cytokines such as monocyte chemoattractant. Contemporaneous low levels of high density lipoproteins (HDLs) implicate a reduction of reverse cholesterol transport from the arterial wall, specifically from lipid-laden macrophages, with excess lipid accumulation in the vessel wall and reduced inhibition of the LDLs oxidation. Therefore the first atherosclerotic lesion can progress towards fibrous, fibroatheromasic and finally towards fibrocalcific plaque and eventually undergo possible complications in various phases. Several growth factors, e. g. platelet-derived and insulin like factors, thrombin, and angiotensin II, produced by activated platelets, macrophages, and dysfunctional endothelial cells, are potent mitogens and characterize early atherogenesis, vascular flogosis, and plateletrich thrombosis in the site of the endothelial lesion. During the evolution of atherosclerotic plaque, the entry and egress of lipoproteins and leukocytes have a complex balance. However the cell proliferation and cell death, extracellular matrix production and remodeling, and finally calcification and neovascularization contribute to lesion formation. The process of atherosclerosis begins in childhood with the development of fatty streaks and progresses in the adult, more commonly among men than women. Multiple risk factors are identified and play a role in the pathogenesis of atherosclerotic lesions. They are divided into modifiable and non-modifiable risk factors. Important modifiable factors are: hyperlipidemia, hypertension, diabetes mellitus, cigarette smoking, obesity. New risk factors seem to play an incompletely cleared role-see the C-reactive protein and fibrinogen level, or the lipoprotein (a). However the results of prospective studies have been discordant and have not proved the relationship between this new factors and atherogenesis. Therapy: In the first step the life style of the patients can be modified: a proper dietetic regimen should be recommended and, in patients with obesity or overweight, the weight loss. Likewise, mainly in sedentary subjects, a suitable physical activity should be indicated with the orders of the weekly protocols. Both primary and secondary prevention of atherosclerosis determine a significance ratio costeffectiveness. In consideration of complex and multifactorial physiopathological aspects of atherosclerosis, a rationally valid therapeutic approach to this syndrome should be based on global risk factor

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 intervention, including the medical treatment of hypertension, diabetes mellitus, and cigarette smoking. The treatment with antiplatelet agents and antioxidant therapies, the amino acid supplementation, the administration of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, has been able to prevent or, at least, slow the progression of atherosclerosis in several studies. It is particularly important to reduce the circulating lipid levels using, in the first step, HMG-CoA reductase inhibitors alone or in combination with ezetimibe. Derivatives and nutritional agents, e.g. omega-3polyunsaturated fatty acid can be used after nicotinic acid. Colestipol and bile acid sequestrants have less importance. The fibric acids derivatives have an incompletely understood role. We have very convincing evidences that the reduction of serum cholesterol and the treatment of dyslipidemia can reduce the risk of coronary heart disease and overall mortality. Moreover in diabetic patients the strict glicemic control is beneficial especially in retarding the progression of microangiopathy, on the contrary it is difficult to confirm its effects in the prevention of macroangiopathy. In hypertensive patients pharmacological therapy can be able to reduce the incidence of stroke and, in a smaller measure, atherosclerotic cardiovascular disease. All the major class of anti-hypertensive drugs are used, but at the present moment the best evidences regarding, for example, the reduction of the carotid intima-media thickness are for the calcium antagonists and angiotensin II receptor antagonists. ACE-inhibitors and beta-blockers are more efficacious than diuretic, but not differences have been reported as regards the placebo.

The management of hypertensive crises P. Mario Sergio Department of Internal Medicine and Medical Specialities I University of Rome Sapienza, Rome, Italy Introduction: The critical elevation of blood pressure (BP) obliges to start a suitable and rapid treatment to prevent serious damages to target organ (brain, heart, kidney, and arteries). Abrupt falls in pressure should be avoided, and the goal of immediate therapy is to reduce diastolic pressure only to approximately 110 mm Hg, specially in elderly people and in patients with known cerebrovasculopathy. The hypertensive crises (HC) are differentiated into hypertensive emergencies (HE) and hypertensive urgencies (HU). The HE are characterized by the evidence of symptoms of the organ damage, therefore it is necessary an admission to an intensive care unit and to start a therapy with parenteral anti-hypertensive drugs. On the contrary the HU can be treated with oral therapy, since symptoms of organ damage in progress are absent. The reduction of the blood pressure can be obtained more gradually over 12 to 24-48 h also in ambulatory system. Our aim is to report the current opinions on the management of HC and to identify the best therapy at the state of the current knowledges. Therapy of HU: First step is to reduce gradually BP and minimize the risk of organ hypoperfusion. Several oral agents can be particularly appropriate to treat HU in an Emergency Department. Captopril, an angiotensin converting enzyme inhibitor, is well tolerated and able to reduce within 15 to 30 min BP when it is administered sublingually at a dose of 25 mg, which can be repeated after 1 to 2 h. The hypotensive response can be enhanced by the contemporary administration of a Henle loop diuretic, such as furosemide. Contraindications are: renal artery stenosis; adverse effects: acute renal failure, angioedema. Clonidine stimulates a2-adrenergic receptors in the brain and inhibits the efferent sympathetic activity with decreasing of systemic vascular resistances; its onset of action is rapid, within 30-60 min after oral administration, with maximal effect in 2-4 h. A loading dose of 0.1-0.2 mg can be followed by administration of 0.1 m hourly for several hours until a suitable BP level is

S339 reached or a maximum dose of 0.7 mg has been given. It is contraindicated in CHF, 2nd or 3rd degree heart block; its adverse effects are drowsiness, sedation, tachycardia, dry mouth. Labetalol is an agent with combined a-b adrenergic block and it is orally efficacious and good tolerated in a dose of 200-400 mg, eventually repeated every 2-3 h. The pharmacological effects clear within 2-4 h; the maximal dose is 1200 mg. It is contraindicated in asthma, COPD, bradycardia; its adverse effects are: bronchoconstriction, bradycardia etc. Nifedipine: it is a dihydropyridine calcium-channel antagonist, most studied for a rapid control of BP elevation. Up to few years ago it has been the most frequently used agent for acute BP lowering in hospitalised patients. The risks of serious adverse effects, mainly with sublingual administration, such as retinal ischemia, acute coronary events or ischemic stroke, induce to avoid the administration of nifedipine short-acting because of a possible rapid uncontrolled BP reduction. Even so this practice is still extensively diffused. Nitroglycerin: it is the agent of choice in unstable angina and immediate treatment of pain during acute myocardial infarction; moreover it is still used for the treatment of left ventricular insufficiency and pulmonary edema: it is rapidly absorbed sublingually at the dose of 0.30.6 mg; the onset of action is within 5 min. It is contraindicated in aortic stenosis and its more common side effects are: headache, hypotension etc. Losartan: it is an highly selective antagonist of the angiotensin II-receptors. An oral dose of 50 mg PO seems to produce better results than lower doses. The onset of action is within 1 h and it protracts for 12-24 h. It is contraindicated in pregnancy (2nd 3rd trimesters); possible allergic adverse effects are rare. Other oral agents such as methyldopa, valsartan, phenoxybenzamine, and direct vasodilators, including minoxidil and hydralazine, has not been studied, but seem to have a little or any role in HC. Therapy of HE: The major HE are the following: Hypertensive encephalopathy; Hypertensive left ventricular failure; Hypertension with myocardial infarction or unstable angina; Hypertension and aortic dissection; Severe hypertension associated with subarachnoid hemorrhage or cerebrovascular accident; Crisis associated with pheochromocytoma; Use of recreational drugs, such as amphetamines, LSD, cocaine or ecstasy; Hypertension peri operatively; Severe pre-eclampsia or eclampsia. The ideal agent should be a fast acting, rapidly reversible, and titratable drug, if possible, without significant side effects. Diazoxide and nitroprussiate are traditional drugs for the use in EC but because of the side effects and severe toxicity are used only when other intravenous agents are not available, in specific clinical circumstances and in patients with a normal renal and hepatic function. Nitroglycerin can be also used IV; its indications has been described above. Labetalol IV is administered at the dose of 20 mg over 10 min; among b-blockers esmolol (a selective blocker of b1 receptors) is interesting both for the rapid onset of action and for brief half-life. Loading dose is 25-500 (50-1000) lg/kg IV infused over 1-3 min (maintenance infusion lg/kg: 50 lg/kg/min with increases, if necessary, up to 300 lg/kg/min and particularly in severe postoperative hypertension). Enalaprilat (in Italy it is available Quinaprilat) can be used at an initial dose of 0.625-1.25 mg IV with initial effects within 15 min. Nicardipine is used at an initial dose of 2 mg IV, then 4 mg/h. Trimethaphan is used now only in aortic dissection. Clevidipine (not available in Italy) has recently be approved for intravenous use in treating severe hypertension. Hydralazine is indicated particularly in eclampsia. Phentolamin, an adrenergic inhibitor has special indications in cathecolamine excess at a dose of 5-15 mg IV. Urapidil, an a1-receptor blocker, 5-HT1Areceptor agonist, used at a dose of 12.5-25 mg IV, is particularly effective in the treatment of pulmonary edema. Finally Fenoldopam, a dopaminergic receptor agonist used at an initial dose of 0.05-0.1 lg/kg per min, seems to be quite safe and good tolerated: it is indicated in patients with renal insufficiency. The use of diuretics (generally furosemide) is somewhat controversial and should be established in relation to clinical conditions.

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Prognostic value of the extent of mitral annulus longitudinal excursion in all amyloidosis

NOX2-Mediated arterial dysfunction in smokers: effect of dark chocolate

S. Perlini1,2, F. Salinaro1, F. Musca1, R. Mussinelli1, M. Boldrini1, A. Alogna1, A. Raimondi1, P. Milani2, P. Russo2, G. Palladini2, G. Merlini2

L. Perri, R. Carnevale, E. Catasca, T. Augelletti, R. Cangemi, F. Albanese, M.M. Palumbo, C. Piccheri, C. Nocella, P. Pignatelli, L. Loffredo

Clinica Medica II, Dipartimento di Medicina Interna e; 2Centro per lo Studio e la Cura delle Amiloidosi Sistemiche, Fondazione IRCCS Policlinico San Matteo, Universita` d Pavia, Pavia, Italy

1

Introduction and Aim: Systemic amyloidoses are characterized by extracellular deposition of insoluble fibrils in various tissues. Clinical presentation is variable, depending on the extension of deposits and on the extent of organ dysfunction, and it often manifests as a systemic disease. In AL amyloidosis, the amyloidogenic protein is an immunoglobulin light chain or a fragment of an Ig light chain that is synthesized by clonal plasma cells in bone marrow. Cardiac involvement is not only frequent but it is also the most common cause of death. Despite extensive cardiac involvement, global systolic function is preserved until the later stages of the disease, characterizing a picture of diastolic heart failure with normal ejection fraction. In contrast, there is a profound diastolic dysfunction. Since regional systolic function may be easily measured by longitudinal excursion of the mitral annulus, aim of the present study was to assess this parameter in AL amyloidosis and to evaluate its prognostic value. Methods: We enrolled 295 consecutive never-treated subjects, in whom a first diagnosis of primary AL amyloidosis was concluded between 2008 and 2009, according to the International Society of Amyloidosis criteria. The cohort was divided into two groups depending on the presence (n = 193) or the absence (n = 102) of cardiac involvement. Cardiac echo-color Doppler data were evaluated at diagnosis, and longitudinal excursion of the mitral annulus at the septum (MAPSE) and lateral wall (LAPSE) was assessed by M-Mode in the apical four-chamber view. Prognosis was assessed after a median follow up of 477 days. Results: Cardiac amyloidosis was associated with marked diastolic dysfunction and preserved ejection fraction. When compared with patients without myocardial involvement, cardiac AL patients showed a marked depression of both MAPSE and LAPSE (7.2 ± 2.3 vs. 12.3 ± 2.1 mm, and 9.5 ± 1.9 vs. 14.7 ± 2.2 mm, respectively; p \ 0.01 for both). After receptor-operated curve analysis to identify the best cut off value for the diagnosis of cardiac involvement, survival analyses were performed. After a median follow-up of 477 days, Kaplan–Meier survival analysis revealed a significantly higher mortality in the groups with depressed MAPSE and LAPSE (p \ 0.001 for both).

CARDIAC DEATH

Dipartimento di Medicina Interna e Specialita` Mediche, ‘‘Sapienza’’ Universita` di Roma, Roma, Italy Arterial dysfunction is a hallmark of early atherosclerosis. Nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, one of the most important cellular sources of reactive oxygen species, may be implicated in artery dysfunction. Cocoa exerts beneficial cardiovascular effects but the mechanism is still unclear. The goal of the present study was to investigate whether the beneficial antioxidant effect of dark chocolate can induce an improvement of endothelial function by oxidative stress reduction mediated by NOX2, the catalytic core of NADPH oxidase. We investigated whether in smokers dark chocolate elicits artery dilatation via down-regulation of NOX2. Flow mediated dilation (FMD), oxidative stress, as assessed by urinary isoprostanes excretion, nitric oxide (NO) generation, as assessed by serum levels of nitrite/nitrate (NOX), and NOX2 activity as assessed by blood levels of soluble NOX2-dp (sNOX2-dp) and serum epicatechin were studied in 20 smokers and 20 healthy subjects (HS). Patients were randomly allocated to 40 g dark chocolate ([85% cocoa) or 40 g of milk chocolate (B35% cocoa), in a single-blind, crossover design. FMD, urinary isoprostanes, NOX and sNOX2-dp were assessed at baseline and 2 hours after ingestion of chocolate. At baseline smokers had lower FMD and NOX and higher sNOX2-dp compared to HS (p \ 0.05). After dark chocolate intake, urinary isoprostanes and sNOX2-dp significantly decreased (from 33.25 ± 5.0 to 23.65 ± 3.9 pg/ml, p \ 0.001, and from 315.4 ± 20.4 to 278.65 ± 27.2 pg/mg creatinine, p \ 0.001, respectively) and FMD and NOX significantly increased in smokers (from 3.8 ± 3.1 to 7.9 ± 4.3%, p \ 0.001, and from 13.38 ± 4.7 to 20.09 ± 6.4 lM, p = 0.001, respectively) but not in HS. No changes of the above mentioned variables were observed after milk chocolate in smokers. Multiple linear regression analysis showed that in smokers the only independent predictive variable associated with D of FMD was D of sNOX2-dp (SE = 0.117; standardized coefficient b = -0.356; p = 0.02). Serum epicatechin increased in either group only after dark chocolate assumption reaching values higher than 0.1 lM (from 0.43 ± 0.35 nM to 118.2 ± 53.1 nM, p \ 0.001 and from 0.45 ± 0.35 nM to 120.9 ± 54.2 nM, p \ 0.001 respectively). Platelets from smokers, but not from HS, showed lower p47phox translocation to platelet membrane and higher NOX when incubated with 0.1-10 lM epicatechin. This study provides evidence that the beneficial effects of cocoa on endothelial function are most likely due to a decrease of NOX2-generated oxidative stress.

CARDIAC DEATH

100

Survival probability (%)

100

80 60 40

p<0.001

p<0.001

60

P. Pesce1, S. Gaiani1, M. Sandri3, T. Zaglia3, M. Mongillo3, C. Sarais2, D. Sacerdoti1

40

MAPSE < 9 mm MAPSE > 9 mm

20

Echocardiographic evaluation of an hypertrophic cardiomyopathy mice model

80

20

0

LAPSE < 11,2 mm LAPSE > 11,2 mm

1

0 0

200

400

600 Time

800

1000

1200

0

200

400

600 Time

800

1000

1200

Conclusion: Despite preserved ejection fraction, regional systolic function is depressed in cardiac AL amyloidosis. This abnormality can be identified by the simple M-Mode analysis of longitudinal excursion of the mitral annulus, that can be easily performed in any echocardiographic laboratory. Notably, the extent of longitudinal systolic dysfunction has a profound impact on patients’ prognosis.

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Department of Clinical and Experimental Medicine, University of Padova; 2Department of Cardiological, Thoracic and Vascular Science, University of Padova; 3Venetian Institute of Molecular Medicine, Padova, Italy Background and Aim: Atrogin-1 (AT-1), an ubiquitin-ligase involved in protein degradation in skeletal and cardiac muscle cells, is central in mechanisms of hypertrophic responses. AT-1 knock out mice (ATko) are transgenic animals lacking AT-1. They show a

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reduced rate of muscle atrophy after denervation. This model is used to study muscle atrophy related to diabetes, starvation and denervation, myopathies due to alteration of autophagy, cardiac hypertrophy signalling pathways. These mice develop right and left ventricular hypertrophy at anatomopathological analysis. It is not known whether it is possible to show cardiac abnormalities in vivo, by echocardiography. This was the aim of the study. Materials and Methods: 16-month-old ATko (n = 7) and wild-type (n = 5) mice underwent transthoracic echocardiography (Visualsonics Vevo 2100 with 30 mHz linear probe). Atria length (Atria L) and antero-posterior diameter (Atria AP), inter-ventricular septum (IVS) and left ventricular posterior wall (LVPW) thicknesses, left ventricle internal diameter (LVID) and maximal left ventricular length (LV length) were measured in systole (s) and in diastole (d) from the long axis B-mode image, according to standard procedures. LV mass (LV Mass) and LV corrected mass (LV Mass cor) were calculated using a corrected cube formula. Systolic and diastolic left ventricular volumes were calculated according to the Simpson’s method (Simp), Stroke volume (SV), cardiac output (CO) and ejection fraction (EF), were determined using the parameters of LV end diastolic and LV endsystolic volumes. Data were expressed as mean ± SD and analyzed by Student’s t-test. Results: All results are shown in the Table

Wild-type (n = 5)

ATko (n = 7)

p (t-test)

LVPW d (mm)

0.85 ± 0.2

1.23 ± 0.2

\0.01

LVPW s (mm)

1 ± 0.2

1.5 ± 0.5

\0.01

Length d (mm) Lenght s (mm)

7.3 ± 0.5 6.3 ± 0.7

5.7±0.3 5.1 ± 0.6

\0.001 \0.01

LV mass (mg)

133 ± 23

169 ± 38

n.s.

LV mass corr (mg)

107 ± 19

133 ± 31

n.s.

Atria AP(mm)

2.1 ± 0.3

4.3 ± 0.4

\0.01 \0.01

Atria L (mm)

2.9 ± 1.4

5.5 ± 0.4

CO (ml\min)

11.5 ± 3.2

15.7 ± 11

n.s.

55 ± 12

60.5 ± 11

n.s.

EF %

Conclusions: 16 month-old AT1-KO mice show a ventricular hypertrophic cardiomyopathy with atrial dilatation and without systolic dysfunction at echocardiography. These alterations resemble anatomo-pathological findings.

An insidious rash vasculitis-like masked the presence of atrial myxoma G.A. Piccillo*, G. Caravaglios**, G. Failla**, A. Milazzotto***, A. De Luca***, E.G.M. Mondati****, P. Caponnetto****, R. Polosa****, G. Gasbarrini***** Department of Emergency Medicine*; Division of Neurology**; Division of Cardiology*** of Cannizzaro Hospital, Catania; Department of Internal Medicine, University of Catania****; President of the Italian Association in Experimental Medicine***** Introduction: An atrial myxoma is a benign tumor found in the heart, commonly in the upper left or right side. It grows on the atrial septum

of the heart. Myxomas are the most common type of primary heart tumor. The tumor is derived from multipotential mesenchymal cells and may cause a ball valve-type obstruction. About 75% of myxomas occur in the left atrium of the heart, usually beginning in the wall that divides the two upper chambers of the heart. The rest are in the right atrium. Right atrial myxomas are sometimes associated with tricuspid stenosis and atrial fibrillation. Myxomas are more common in women. About 10% of myxomas are passed down through families (inherited). Such tumors are called familial myxomas. They tend to occur in more than one part of the heart at a time, and often cause symptoms at a younger age than other myxomas. Symptoms may occur at any time, but most often they accompany a change of body position. Symptoms may include shortness of breath with activity platypnoea, difficulty breathing in the upright position with relief in the supine position, Paroxysmal nocturnal dyspnea, breathing difficulty when asleep dizziness, fainting, palpitations, sensation of feeling your heart beat, chest pain or tightness, sudden death (in which case the disease is an autopsy finding!). The symptoms and signs of left atrial myxomas often mimic mitral stenosis. General symptoms may also be present, such as cough, fever cachexia, involuntary weight loss, general discomfort, joint pain, blueness of skin, especially the fingers (Raynaud’s phenomenon). These general symptoms may also mimic those of infective endocarditis. Despite being the most common benign intracardiacac tumour, with an excellent prognosis after surgical exicition the incidence of atrial myxoma is unknown but surely it represents a very rare report in Emergency Medicine. Case report: Here we report a case of 62 year-old woman admitted to our Department for sudden onset of rash erythematous to legs suggesting a skin vasculitis. All the laboratory tests resulted normal and also the antibodies screening test resulted negative. The rash disappeared rapidly so that we discharged our patient in healthiness. Normal resulted one more time laboratory data and EKG. But six months later she was readmitted to Hospital due to onset of transient hemianopsia and dysarthria complicated with right occipital frontal headache. The neurological evaluation seemed negative normal but brain TC scan revealed two hypodense left frontal and occipital lesions although the carotid ultrasound was normal. Our patient started treatment on antithrombotics and our second hypothesis was a case of cerebral ischemic attack. Before our second patient’s discharge, she was submitted to echocardiography which pointed out the presence of a left atrial mass highly suggesting a myxoma, conditioning, probably, cerebral and peripheral embolization. For this reason the patient was transferred to Cardiosurgery Division and submitted to excision of the atrial mass and luckily the histology and immunehistochemical examen confirmed it treated of a myxoma. Now, after six months of follow up our patient is still in healthy. Discussion: Diagnosis is suspected when is possible detect with stethoscope. A ‘‘tumor plop’’ (a sound related to movement of the tumor), abnormal heart sounds, or murmur may be heard. These sounds may change when the patient changes position. Right atrial myxomas rarely produce symptoms until they have grown to be at least 13 cm (about 5 inches) wide. Tests may include echocardiogram and Doppler study, Chest x-ray, CT scan of chest, heart MRI, left heart angiography, right heart angiography, EKG may show atrial fibrillation, blood tests may show anemia and leukocytosis. The ESR is usually increased. The treatment consists in tumor surgically remotion and in some cases in consensual mitral valve replacement. Myxomas may come back if surgery did not remove all of the tumor cells. Although a myxoma is not cancer, complications are common. Untreated, a myxoma can lead to an embolism since tumor cells breaking off and traveling with the bloodstream, which can block blood flow. Myxoma fragments can move to the brain, eye or limbs. If the tumor grows inside the heart, it can block blood flow through the mitral valve and cause symptoms of mitral stenosis. This may require emergency surgery to prevent sudden death. We ever must consider when the patients present with unexplained systemic symptoms and

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S342 signs of embolisation the possible cardiac origin. Although atrial myxoma is rare, when there is the consistent suspect of the disease, it is necessary to obtain cardiac imaging to disclose the possible origin of embolisation.

Serum levels of vitamin D in patients with grade 1 essential hypertension L. Polidoro, L. Petrazzi, V. De Santis, R. Scipioni, R. Del Pinto, D. Carnevale, G. Properzi, C. Ferri Division and School of Internal Medicine, University of L’Aquila, San Salvatore Hospital, L’Aquila, Italy Background: Hypovitaminosis D is common in the Italian population, probably due to insufficient exposure to ultraviolet B rays. Vitamin D regulates approximately 3% of the human genome and many observational studies support the hypothesis that it is also involved in the pathogenesis of cardiovascular disease and hypertension. In particular, vitamin D contributes to the determinism of blood pressure by its ability to inhibit the renin-angiotensin-aldosterone system, to protect the vessel wall and obviously to contribute to the calcium homeostasis. On this basis, the aim of our study was to evaluate serum levels of vitamin D in patients with recently diagnosed grade 1 essential hypertension. Methods: We selected 35 patients (26 M and 9 F) with grade 1 essential hypertension and 35 age- and sex-matched normal controls. All patients were evaluated for anthropometric parameters, lipid profile, fasting glucose and insulin concentrations, and serum levels of vitamin D by standard laboratory methods. Results: The group of patients (mean age ± SD: 47 ± 10.30 years) with grade 1 essential hypertension (mean sitting SBP ± SD = 141.64 ± 11.53 mmHg – mean sitting DBP ± SD = 91.85 ± 9.47 mmHg) had mean serum levels of vitamin D at the lower limits of the normal range and lower than the control group (34.97 ± 7.41 versus 50.10 ± 6.25 ng/ml, respectively, p = 0.007). Inverse correlations were found in the hypertensive group between serum levels of vitamin D and BMI (r -0.538, p = 0.02), fasting insulin levels (r -0.698, p = 0.007) and the index of insulin resistance HOMA-IR (r -0.678, p = 0.0139). No correlations were found in normal subjects. Discussion: Our study shows that relatively young, recently diagnosed patients with grade 1 essential hypertension had decreased serum levels of vitamin D. This finding suggests that vitamin D is involved in the development of hypertension and its supplementation might be considered in these patients. Both of these hypotheses are markedly reinforced by the finding that patients with hypertension also manifest with inverse correlations between vitamin D levels and BMI, fasting insulin levels and HOMA-IR.

Association of fatty liver and carotid lesions with metabolic syndrome: A population based study (SLMS) S. Pretolani, V. Arienti, F. Lorenzini, L. Baldini, G. Giuliani Piccari, C. Dellacasa1, M.C. Baldacci2, M.R. Gatto3, I. Marini3 1 Medicina Interna A e Laboratorio Analisi, Ospedale Maggiore Bologna, CINECA; 2Bologna, Assessorato Salute Comune San Lazzaro; 3Dipartimento Scienze Odontostomatologiche, Universita` di Bologna, Bologna, Italy

To determine the prevalence of MS and its association with fatty liver and carotid lesions in the general population of San Lazzaro di Savena, a 30,000 inhabitants town in the neighbourhood of the Bologna.

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Methods: a sample (2611 subjects with a confidence of 99% and a 2.5% precision) of the whole adult population (age 20-89) was randomly selected from the Registry Office of San Lazzaro di Savena, using as strata sex, age and level of education (elementary, middle, high, university degree) as a surrogate of level of income. Population was informed of the study by media advertisement and meetings with local general practitioners. From October 2008 the selected subjects were recruited by letter and phone call and were invited to present on appointment at the local Health District. During this visit each subject underwent to: anthropometric measurements, blood pressure evaluation, administration of a questionnaire on lifestyle habits (semiquantitative measures of diet components, alcohol intake and physical activity) and family/personal history of diseases; blood and urine samples for biochemical tests, liver and carotid ultrasound for the evaluation of fatty liver (score 0-3, Hamaguchi 2007), presence of plaques and evaluation of intima-media thickness (IMT, Mannheim Consensus 2006). Presence of MS was defined according to NCEP-III (2001). Statistical analyses were performed by using v2 and Mann– Whitney U test as appropriate. RESULTS: We report here the results on the first 1156 recruited subjects. The response rate was 77% with a F/M ratio of 57/43%. The prevalence of MS was 11% in males (55/ 489) and 9% in females (61/667) and increased significantly with age (M :v2 14.4, p = 0.025; F: 29.8 p = 0.0001). Fatty liver was found in 245/489M (50%) and in 219/667 F (33%) and its score was associated with MS (v2 34.8 in M, 59.9 in F, p = 0.0001). The MS prevalence was higher (15%) when carotid plaque was present either on right or left side (v2 8.668, p = 0.003). The c-IMT was significantly higher either on left (1.13 ± 0.03 vs 0.99 ± 0.01) or right side 1.08 ± 0.03 vs. 0.96 ± 0.0) when MS was found (Mann–Whitney test p = 0.0001). Conclusions: a) the prevalence of MS in the general population of San Lazzaro di Savena increases with age and is associated with fatty liver and carotid lesions in both sexes; b) the large proportion of subjects with fatty liver and carotid lesions (particularly C-IMT values) may represent a determinant for the high risk of developing cardio-cerebrovascular diseases in this geographic area.

Role of Platelets in NOX2 activation mediated by TNFa in patients with heart failure M. Proietti, R. Carnevale, S. Bartimoccia, C. Calabrese, M. Del Ben, R. Russo, P. Pignatelli, M. Schillizzi, S. Basili, E. Catasca, R. Cangemi Divisione I Clinica Medica, ‘‘Sapienza’’ University of Rome, Rome, Italy Background: Tumor Necrosis Factor alpha (TNF a) may contribute to the deterioration of cardiovascular function in heart failure (HF) through various mechanisms, including the generation of reactive oxygen species (ROS). NADPH oxidase is the major source of ROS in the vascular system, but the interplay between TNFa and NADPH oxidase activation is elusive. As platelets possess the enzyme NADPH oxidase, they represent an important tool to investigate the interplay between NADPH oxidase and TNFa in patients with HF. Methods and Results: Serum NOX2, the catalytic core of NADPH oxidase, and plasma TNFa were measured in 120 HF patients and in 60 healthy subjects (HS). Compared with healthy subjects, HF patients had higher blood levels of NOX2 and TNFa with a progressive increase from NYHA I to NYHA IV classes. NOX2 blood levels were independently associated with TNFa in HF patients. An in vitro study, performed on platelets from a subgroup of HF patients, showed that TNFa, at concentrations commonly found in HF patients peripheral circulation, activated platelet NOX2. Thus, TNFa increased ROS production, reduced the expression of NOX2 on platelet surface and increased the extracellular levels of NOX2. These

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 phenomena were inhibited by the NOX2 specific blocking peptide gp91ds-tat. Conclusions: The study provides evidence that circulating NOX2, as well as the activation of NOX2 on platelets, is increased in HF likely as a consequence of the underlying inflammatory process.

S343 On December 5th 2010 the patient arrives at the Emergency Room (E.R.), suffering from syncope with head injury and intense dyspnea. In the Emergency Room (E.R.) the following tests are carried out: • •

Anoxia-reoxygenation enhances platelet TXA2 production via ROS-generated NOX2: effect in patients undergoing elective percutaneous coronary intervention

•

V. Raparelli, P. Pignatelli, G. Tanzilli*, E. Mangieri*, R. Carnevale, C. Nocella, E. Catasca, S. Di Santo, D. Pastori, P. Ferroni**, S. Basili

•

Divisione I Clinica Medica, ‘‘Sapienza’’ University of Rome *Department of the Heart and Great Vessels ‘‘Attilio Reale’’; ‘‘Sapienza’’ University of Rome; **Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Roma, Italy Objective: Platelets undergoing anoxia-reoxygenation (AR) simultaneously increase reactive oxidant species (ROS) and Thromboxane (Tx) B2. Our aim was to assess if there is an interplay between activation of NOX2, the catalytic sub-unit of NADPH oxidase, and platelet TxB2 in vitro and in vivo. Methods and Results: Platelets that underwent AR had enhanced ROS. This was associated with NOX2 activation and was inhibited by incubation with NOX2 blocking peptide. AR was associated with TxB2 and isoprostanes production, which were inhibited by NOX2 blocking peptide, vitamin C and the inhibitor of PLA2. Platelet incubation with 100 lM aspirin fully prevented ARinduced TxA2 but did not affect isoprostane production. We included fifty-six aspirin-treated patients undergoing elective percutaneous coronary intervention (PCI), who were randomly allocated to receive either placebo or i.v. infusion of 1 g vitamin C. Blood TxB2, isoprostanes and soluble NOX2-derived peptide, a marker of systemic NADPH oxidase activation, significantly increased after 60’ and 120’ from PCI in placebo-treated but not in vitamin C-treated patients. Conclusion: AR is associated with over-production of platelet TxB2 and isoprostanes, which fineis dependent upon NOX2-dependent ROS generation. Low doses of aspirin are unable to prevent TxB2 formation in patients who undergo PCI.

A strange cerebrovascular accident M. Renis, A. Schiavo Medicina Interna, P.O. Cava de’ Tirreni, A.O.U. ‘‘S.G.di D. e R. d’A.’’, Salerno, Italy Introduction: An accurate evaluation of the clinical-anamnestic picture is always important; sometimes beyond the contrasting results of some instrumental investigation in order to come to a correct diagnosis rapidly. The authors present a case-report with clinical-instrumental peculiarities. Clinical case: A.E. female, 86 years old. Anamnesis: myocardial infarction in 2000, hypertension, chronic cerebral vasculopathy, carotid atherosclerosis. Two months earlier: not clearly defined ‘‘arteriopathy’’. Home treatment: ticlopidine, ACE-inhibitor, calcium channel blocker and statine.

•

A/B balance, with oxygen support at 12 lt/min: pH 7,25, pCO2: 35, pO2: 68, HCO3-: 15,3, Lact 7,6; Electrocardiogram: ‘‘Regular sinus rhythm, previous necrosis in antero-infero-septal seat’’; Altered haematochemical tests: WBC 17000 c/mmc, glycaemia 178 mg/dl, AST 94 U/L, ALT 48 U/L. Chest X-ray: ‘‘Shaded parenchymal thickness in the left upper area. Enlarged cardiac silhouette’’. TC cranium: ‘‘Ischemic results in the left parieto-occipital seat’’.

Clinically improved with steroid treatment, diuretic and oxygen giving, the patient is admitted into the Internal Medicine Division with the following diagnosis: ‘‘Cerebro-vascular accident. Dyspnea’’. A cortisone and antibiotic therapy is established for the probable bronchopneumonic process highlighted by X-ray; it’s required D-dimers dosage (9000 results); it’s then established a treatment with enoxaparin 6000 U twice/day and is also required a perfusive pulmonary scintigraphy. An echocardiogram is required (as in the meantime the troponin increases up to 1,66), which highlights: ‘‘Concentric Hypertrophy of the left ventricle wall, septo-apical apocinesia (Ejection Fraction: 40-45%); Left atrium and right sections in the limits, pericardium unharmed’’. A/B Balance in air environment shows: pH: 7,37, pCO2: 34, pO2: 45, HCO3-: 19,7, lact: 3. It is also diagnosed a monoclonal gammopathy: there is an anomalous peak of the protein electrophoresis in the gamma area which results monoclonal IgG-lambda at the serum-immunofixation. On December 9th 2010 the pulmonary scintigraphy is carried out. It highlights: ‘‘Right lung: large perfusive deficit, monoperfuse parenchyma in the lower side only; left lung: perfusive deficit at the apical and anterior segments of the superior lobe’’. In the following days a clinic-laboratorial improvement is registered. The patient is therefore discharged on December 22nd 2010 with the following diagnosis: ‘‘Pulmonary thromboembolism complicated by a grave respiratory failure, chronic cerebral vasculopathy, monoclonal gammopathy (diagnostic close examination in progress)’’. Discussion: The hospitalization diagnosis when admitted into the department is: ‘‘Cerebro-vascular accident. Dyspnea’’. Leukocytosis and chest X-ray would suggest a pneumonia. Furthermore the mixed acidosis (the respiratory compensation is below what expected), instead of the classic hypoxic hypocapnic respiratory alkalosis, the absence of dilatation of the right sections at the echocardiographic would not lead to think of a pulmonary thromboembolism. However a careful examination of the beginning symptoms (swoon + sudden and persistent dyspnea) and of the anamnesis (previous deep venous thrombosis?) immediately lead to the suspect of pulmonary thromboembolism, determined by perfusive scintigraphy. The persisting of the metabolic acidosis, after the first phase linked to the shock hyperlattatemy, can be explained by the presence of blood neoplasia. Conclusions: If not promptly recognised and treated, pulmonary thromboembolism can cause elevate mortality. It is a challenge for the doctor, in his daily practice, as symptomatology, objectivity and instrumental exams are non specific, especially in old patients. The above case shows how a cautious evaluation of the symptoms and the anamnesis has allowed, despite of a different diagnosis at the arrival and the apparent contradiction in the results of some instrumental exams, not to have an immediate diagnostic suspect and therefore a sure diagnosis, surely not simple, and to practise an adequate treatment for a pathology causing an elevate mortality.

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HCV infection is an independent risk factors of ischemic cerebral stroke L. Restivo, N. Iuliano, A. Santoro, V. Luiso, G. Li Vigni, A. Ciervo, L.E. Adinolfi Internal Medicine, Second University of Naples, Clinical Hospital of Marcianise, Italy The majority of ischemic cerebral events are due to cerebral embolism or decreased flow from atherosclerosis of the internal carotid artery, whereas emboli from the heart account for a minority of cases. Cross-sectional studies on the general population showed that the presence of anti-HCV antibodies and/or serum HCV core protein was independently associated with an increased risk of atherosclerosis. These data suggest a possible role of HCV in the development of atherosclerosis. Moreover, it has been demonstrated that HCV RNA sequences were present and replicate within carotid plaques. These findings support a local pro-atherogenic action of the virus and that HCV per se could contribute to the pathogenesis of arterial remodelling. Accordingly, we hypothesize that HCV is associated with ischemic stroke. Thus, the aim of this study was to evaluate the prevalence of HCV infection and associated factors in patients with ischemic cerebral stroke as compared with two, matched for age, control groups: patients with BPCO and patients with an age greater 65 years old with a pathologies different of hepatic diseases. All patients were consecutively admitted to our Unit of Internal Medicine over a period of 18 months. Ischemic stroke was diagnosed on clinical signs and with computer tomography (TC). Patients underwent to carotid doppler to estimate the degree of stenosis in the carotid vessels in the neck. The major risk factors for stroke were evaluated, in particular, hypertension, smoking, serum cholesterol, diabetes, cardiac arrhythmias, IMA. The presence of HCV-ab was assessed and in those positive HCV RNA was determined. Patients were evaluated to assess liver disease. Overall, 532 consecutive patients were included and screened for HCV-Ab: 112 with stroke, 200 with BPCO and 220 with pathologies other than liver diseases. The characteristics and the prevalence of HCV of the three groups are reported in the following Table.

Stroke

Number of patients 112

BPCO

Other non-hepatic diseases

200

220

p\

Age, median yrs (range)

75 (46 - 93) 76 (41 - 93) 78 (65 - 100)

Male sex

52%

70%

59%

Smoking

37%

67%

27%

Hypertension

90%

60%

61%

0.001

Diabetes Serum cholesterol (mg±sd)

63% 174 ± 53

41% 172 ± 53

52% 175 ± 48

0.05

0.05

Atrial fibrillation

27%

15%

16%

IMA

6.8%

5.8%

6.0%

HCV positivity

24.1%

8.5%

8.3%

0.001

An analysis of data of patients with stroke according to presence or absence of HCV showed that in HCV positive patients the male were prevalent (61%, HCV positive vs 49%, HCV negative), whereas there

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was no differences in age (76 yrs vs. 74 yrs), smoking (44% vs. 35%), hypertension (89% vs. 91%), Diabetes (72% vs. 60%), atrial fibrillation (22% vs. 29%), IMA (5.6% vs. 7.3%). There was no difference in inflammatory parameters (CRP and fibrinogen). Hepatic abnormal function tests were observed in 45% of patients HCV positive. HCV positive and HCV negative patients showed different values of serum ALT (64±63 vs 29± 32; p\0.004, respectively) and platelet count (165 ± 66 vs. 226 ± 79; p \ 0.003; respectively). Serum cholesterol levels were significantly lower in HCV positive patients than that observed in HCV negative (140 ± 50 vs. 186 ± 49; p \ 0.001; respectively); a similar trend was observed for serum triglycerides (109 ± 66 vs 138 ± 90; p \ 0,08; respectively). Multivariate analysis using logistic regression analysis showed that HCV was an independent factor associated with stroke (O.R.:1.77; 95% CI.:1.392.24; p \ 0.0001). Conclusions: The preliminary results of this study demonstrate that HCV positive patients have a risk two times higher to develop ischemic stroke despite infected patients had some favourable factors for atherosclerosis such as lower cholesterol levels and platelet counts. HCV plays a pathogenic role in the embolic stroke likely through its localization and replication within carotid plaques causing local inflammation and instability of vascular lesion. Supported by a grant of Regione Campania

Elevated VEGF-plasma levels in mild essential hypertension R. Ria, G. Ficarazzo, F. Stefanutti, G. Ranieri DIMO, Section of Internal Medicine, University of Bari Medical School, Bari, Italy Recent studies report that inflammation plays a pivotal role in the pathophysiology of essential hypertension. Vascular endothelial growth factor (VEGF) is currently discussed as a possible mediator of inflammation. VEGF is a multifunctional glycoprotein which is mitogenic for endothelial cells. It has high affinity with endothelial cells in the macro and microvascular vessels. It is the most important regulator of pathological or physiological angiogenesis and additionally leads to increased vascular permeability. Animal studies have revealed that locally delivery of VEGF after endothelial injury promotes endothelial regeneration, and accelerates the recovery of endothelium-dependent relaxation. Recent studies have claimed that essential hypertensive patients have increased serum VEGF levels. This increase is particularly significant in patients with vascular damage. To investigate the hypothesis that VEGF plays a role as inflammatory mediator in essential hypertension we performed the present study of young patients in a very early stage of hypertension. Fifty never treated patients with mild hypertension (33.5 ± 6.1 years) and 50 healthy controls (32.2 ± 7.1 years) were examined; serum levels of VEGF were measured via commercially available enzyme linked immunoassay (R & D System). Hypertensive showed increased plasma levels of VEGF (p \ 0.05).VEGF positively correlated with mean arterial pressure (r = 0.54, p \ 0.05). In this study, we observed increased plasma levels of VEGF among young patients with mild uncomplicated hypertension who were free of target organ damage. Furthermore a positive correlation between VEGF and mean arterial pressure could be detected. This study suggest that in mild hypertension, inflammatory pathway have already been activated. Our findings add to the general debate regarding the role of VEGF in cardiovascular disease.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Elevated VEGF levels in hypertensive patients support the concept of an abnormal angiogenesis in the pathophysiology of hypertension. In conclusion, the present study seems to suggest new insights into the pathophysiological mechanisms in essential hypertension linking inflammation and abnormal angiogenesis. The increased VEGF levels may be important in the early diagnosis of vascular damage in essential hypertension.

Follicle-stimulating hormone acutely affects vascular function in humans A. Ruvolo, C. Pirozzi, G.A. Lupoli, G. Fertuso, P. Chiola, G. Lupoli, L. Sacca’, R. Napoli Department of Internal Medicine and Cardiovascular Sciences, University Federico II, Naples, Italy Background: In women, menopause is associated with an increase in cardiovascular risk. Several mechanisms have been postulated to be responsible for such an increase, including reduction in estrogens and iron accumulation. However, during the transition from fertility to menopause, several hormonal changes occur that might be potentially involved in the waning of cardiovascular protection in women. Among these changes, the circulating levels of follicle-stimulating hormone (FSH) increase many fold. Endothelial function plays a pivotal role in the prevention of atherosclerosis and in maintaining a low cardiovascular risk. The few data available in vitro showed that the knockout of FSH receptor in rats is not associated with any change in endothelial function in isolated vascular rings. However, the effect of FSH on vascular function have never been studied in humans. Objective: To study the role of FSH in the regulation of vascular function in humans. Methods: In women, the administration of FSH is followed by perturbations of circulating ovarian hormones, making it impossible to isolate the effect of FSH. In contrast, in male, FSH administration is characterized by increase in spermatogenesis, but no changes in other hormones are detected. Therefore, in male subjects the effect of FSH on the vascular bed can be easily evaluated. We studied brachial endothelial mediated (FMD) and non-endothelial mediated (NMD) dilation in 16 healthy males before and at 6 and 24 h after the subcutaneous administration of 300 IU of recombinant FSH (rFSH) or placebo according to a double blind, placebo controlled protocol. Each subject studied underwent the two experiments (FSH or placebo) 4 weeks apart. Results: In the basal state, the 16 volunteers (age 28 ± 2, M ± SE) showed an FMD of 9.3 ± 0.70% and an NMD of 20 ± 2%. FSH administration induced a significant reduction of FMD both at 6 (6.7 ± 0.8%; p = 0.017) and 24 h after the injection (7.5 ± 0.5; p = 0.013, vs. basal). In contrast, NMD was unchanged by FSH administration. As expected, placebo injection did not induce any change in either FMD or NMD Conclusion: rFSH administration affects endothelial function in humans. The data suggest that FSH might play a role in the increase of cardiovascular risk associated with menopause.

Pseudoinfarction pattern in AL amyloidosis: only a diagnostic marker? F. Salinaro1, M. Boldrini1, R. Mussinelli1, A. Alogna1, A. Raimondi1, G. Palladini2, A. Foli2, P. Russo2, F. Musca1, G. Merlini2, S. Perlini1,2 1 Clinica Medica II e; 2Centro per lo Studio e la Cura delle Amiloidosi Sistemiche, Fondazione IRCCS Policlinico San Matteo di Pavia, Pavia, Italy

S345 Introduction and Aim: Amyloidoses are disorders of protein conformation and metabolism that result in tissue deposition of insoluble fibrils, organ dysfunction, and death. In primary systemic amyloidosis (AL), fibrils are composed mostly by the N-terminus of a monoclonal immunoglobulin light chain. Almost two-thirds of AL patients present cardiac amyloidosis at diagnosis, but virtually all eventually die of cardiac-related death. Therefore, cardiac involvement is by far the major prognostic determinant. The 12-leads electrocardiogram (EKG) reflects the generalized infiltrative nature of the disease, with low peripheral voltages, conduction abnormalities such as fascicular block or atrioventricular block of varying degree, and ‘‘pseudoinfarction’’ patterns in the anterior precordial and/or the inferior limb leads. The latter is defined as the presence of QS waves in at least two contiguous leads, in the absence of previous myocardial infarction. Since it represents an index of myocardial scar, as typically shown after myocardial infarction, we hypothesized that a ‘‘pseudoinfarction’’ pattern can identify patients with AL amyloidosis showing a higher extent of cardiac involvement. Aim of the present study was therefore to assess the diagnostic relevance of this simple EKG parameter, and to evaluate its prognostic power in AL patients. Methods: All never-treated subjects in whom a first diagnosis of primary AL amyloidosis was concluded between 2008 and 2010 were enrolled. Diagnosis and assessment of organ involvement were performed according to the International Society of Amyloidosis criteria. To avoid any possible interference of ischemic heart disease on the presence of pseudoinfarction pattern, patients with a positive history of coronary disease, or with regional abnormalities of cardiac wall motion at echocardiography, were excluded from the analysis. The study population included 295 consecutive patients, 193 with and 102 without cardiac involvement. Prognosis was assessed after a median follow up of 477 days.

CARDIAC DEATH 100 80 p<0.0001 60 40 Pseudoinfarction pattern Absent Present

20 0 0

200

400

600 Time

800

1000

1200

Results: Cardiac involvement was associated with a different EKG pattern, with a 63.9% proportion of low voltages, and 38.5% of strain pattern. When compared with non-cardiac AL patients, cardiac involvement was associated with prolonged PQ, QRS and QT intervals (all p \ 0.05), with a prevalence of overt atrio-ventricular block or of complete bundle branch block equal to 24.8% and 28%, respectively. Cardiac AL patients showed a 52.2% prevalence of a pseudoinfarction pattern (p \ 0.001 vs. non-cardiac AL patients), with QS waves in the inferior leads in 15%, in the antero-septal leads in 64%, and in both leads in 21% of patients. Kaplan–Meier survival analysis demonstrated a significantly higher mortality in the pseudoinfarction group when compared with the ‘‘no QS pattern’’ group (p\0.0001). The same trend was nearly preserved considering only patients with myocardial involvement (p = 0.07). In cardiac AL patients, the presence of a pseudoinfarction pattern was associated with a lower peripheral QRS score (p \ 0.001) and with a thicker interventricular septum (p = 0.036), but not with the presence of fragmented QRS, conduction abnormalities, or cardiac peptide serum levels (NT-proBNP and Troponin I).

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S346 Conclusion: Pseudoinfarction pattern has a relevant diagnostic and prognostic power and appears more correlated with heart structure parameters rather than indexes of heart dysfunction. When evaluating patients with AL amyloidosis or with a condition ‘‘at risk’’, such as a monoclonal gammopathy, the analysis of a simple EKG may be a clinically valuable tool. The presence of pseudonecrosis pattern should be integrated with the other EKG, echocardiographic and biochemical parameters that are the cornerstone for an early diagnosis of cardiac amyloid deposition.

Obesity is an independent risk factor for carotid stenosis in cardiac surgery patients A. Savino, L. Sirinelli, A. Berni, S. Berardino, De Antoniis Francesco, S. Del Pace, G.F. Gensini, M. Boddi Dipartimento di Area Critica Medico-Chirurgica, Universita` degli Studi di Firenze, Firenze, Italy Objectives: Reduction of perioperative complications in cardiac surgery occurred thanks to EuroSCORE system, a validated method for calculating predicted operative mortality of patients undergoing cardiac surgery. According to this score, the ultrasound evaluation of extracranial carotid arteries was recommended. This study was aimed at investigating whether in cardiac surgery patients the occurrence [50% carotid artery stenosis according to haemodynamic criteria could be associated to peculiar cardiovascular risk profile. Methods: Five-hundred-sixty-four patients who had been admitted to the Cardiologic Ward of the Department of Heart and Vessels, University of Florence, directed by Prof. Gian Franco Gensini between May 2008 and May 2009, performed ultrasound evaluation of extracranial carotid and vertebral vessels. The degree of stenosis was determined by the data from duplex ultrasound studies according to the Gray-Scale and duplex ultrasound criteria established by a consensus panel convened under the auspices of the Society of Radiology in Ultrasound in San Fransisco in 2002. In 141 patients we could retrospectively analyzed clinical, laboratory and instrumental preoperative data. Data of patients without carotid artery stenosis and with stenosis\50% (non stenotic patients, NSPs) were compared with those of patients with [50% stenosis (stenotic patients, SPs). Results: Fifty-three (9.4%) of the 564 carotid artery ultrasound exams showed[50% stenosis of carotid vessels and all were localized at internal carotid artery. Specifically, 25 (4.4%) showed[70% stenosis, while 28 patients (5%) had a 50-69% stenosis. Among the 141 patients selected from the whole population,[50% carotid stenosis occurred in the 28% and about the half showed [70%) carotid stenosis. SPs had a higher average age (76 ± 7 vs. 69 ± 10 years, p \ 0.001), lower GFR (60 ± 24 vs. 75 ± 32 mL/min, p \ 0.001) and higher prevalence of cardiovascular risk factors (dyslipidemia, arterial hypertension, type 2 diabetes mellitus, overweight/obesity, i.e. BMI [ 25 kg/m2), peripheral arterial disease (PAD) and of previous stroke, when compared to NSPs. Univariate analysis showed overweight/obesity (OR 9.27; IC 3.8522.30; p \ 0.001), PAD (OR 6.58; IC 2.48-17.43; p\0.001), previous stroke (OR 4.13; IC 1.33-12.82; p = 0.014), as stronger predictors of carotid stenosis [50%. The presence of one of the other cardiovascular risk factors or a GFR\50 mL/min was associated with a 2.5-3.5 times higher risk of carotid stenosis [50%. Multivariate analysis selected overweight/obesity along with age as strongest independent predictors of carotid stenosis after adjustment for other covariates. Conclusion: Overweight/obesity select a subgroup of cardiac surgery patients at high risk for hemodynamically significant carotid stenosis probably because in these patients many CV risk factors concur. Preoperative duplex ultrasound studies of the extracranial carotid arteries of these patients should be routinely performed.

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 One-hour post-load plasma glucose levels and diastolic function in essential hypertension A. Sciacqua, S. Miceli, L. Greco, F. Arturi, P. Naccarato, D. Mazzaferro, E.J. Tassone, L. Turano, G. Sesti, F. Perticone Department of Experimental and Clinical Medicine-University Magna Graecia of Catanzaro, Italy Impaired left ventricular relaxation, characterized by a reduced early and increased late diastolic flow, is an early sign of diastolic dysfunction (DD) that provides an independent prognostic information in the general population, as well as in different clinical settings. DD represents the first manifestation of myocardial involvement in diabetes and may also precede the clinical appearance of diabetes itself, so that DD is not exclusively a complication of diabetes but rather a coexisting condition. A plasma glucose value C155 mg/dl for the 1-hour post-load plasma glucose during an oral glucose tolerance test (OGTT) is able to identify subjects with normal glucose tolerance (NGT) at high-risk for type-2 diabetes (T2D). Moreover, 1-hour post-load plasma glucose value is strongly associated with subclinical organ damage, as carotid intimamedia thickness and reduced estimated glomerular filtration rate. Therefore, the aim of the study was to address the question if glucose tolerance status, and in particular 1-hour post-load plasma glucose levels, may affect diastolic function in a group of 161 never treated hypertensive Caucasian subjects. All patients underwent OGTT for the evaluation of glucose tolerance and standard echocardiography. Diastolic function was assessed by pulsed Doppler transmitral flow velocity and tissue Doppler imaging, according with diagnostic criteria proposed by the American Society of Echocardiography. Insulin sensitivity was assessed by Matsuda index. Among participants, 120 were NGT, 26 had impaired glucose tolerance (IGT) and 15 had T2D. NGT C155 had higher left atrium dimensions (18.7 ± 4.6 vs 15.8 ± 4.2 ml/m2; P\0.0001) and IVRT (120.5 ± 40.1 vs 107.5 ± 24.6 ms; P=0.037) than NGT\155. On the contrary, E/A ratio and all tissue Doppler parameters were significantly lower in NGT[155 than NGT\155 subjects. At multiple regression analysis, 1-h glucose resulted the major determinant of left atrium area, IVRT, septal e’, septal e’/a’ ratio, lateral e’ and lateral e’/a’ ratio, explaining respectively 25.6%, 18.2%, 15.2%, 25.2%, 18.3% and 14.8% of their variation. The main finding of this study is that 1-hour post load plasma glucose is associated with left ventricular DD. NGT C155 subjects had a significantly worse diastolic function compared to NGT\155 subjects and similar to IGT and T2D patients. These data allow to identify a new early predictor of subclinical organ damage and emphasize the importance to perform an OGTT in all subjects affected by essential hypertension. Therefore, in order to better stratify the global cardiovascular risk, is important to consider not only the 2-h but also 1-h post load plasma glucose value, which is more strongly associated with DD.

One-hour post-load plasma glucose levels and vascular stiffness in essential hypertension A. Sciacqua, M. Perticone, R. Maio, S. Miceli, G. Carullo, A. Pascale, F. Arturi, G. Sesti, F. Perticone Department of Experimental and Clinical Medicine-University Magna Graecia of Catanzaro, Italy Pulse wave velocity (PWV) is recognized as a surrogate end-point for cardiovascular (CV) morbidity and mortality. A plasma glucose value C155 mg/dl for the 1-hour post-load plasma glucose during an oral glucose tolerance test (OGTT) is able to identify subjects with normal glucose tolerance (NGT) at high-risk for type-2 diabetes (T2D). Moreover, 1-hour post-load plasma glucose value has been associated with carotid intima-media thickness (IMT) and renal dysfunction, that

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 represent subclinical organ damage and independent predictors for subsequent CV events. We addressed the question if 1-hour post-load plasma glucose levels, affects PWV and its central hemodynamic correlates, such as augmentation pressure (AP) and augmentation index (AI), in essential hypertension. For this aim, we enrolled 334 never-treated hypertensives, 203 men and 131 females (age mean ± SD=46.5 ± 9.1). All patients underwent oral glucose tolerance test (OGTT) and insulin sensitivity was assessed by Matsudaindex. PWV, AP and AI were obtained by a validated system TM (Sphygmocor ; AtCor Medical, Sydney, Australia) that employs high-fidelity applanation tonometry (Millar) and appropriate computer software for the analysis of pressure wave. Among participants, 249 were NGT, 64 had impaired glucose tolerance (IGT) and 21 had T2D. According to 1-hour post-load plasma glucose cut-off point of 155 mg/dl, we divided normotolerants in: NGT\155 (n=175) and NGTC155 (n=74). NGTC155 had a worse insulin sensitivity (Matsuda-index 58.7 ± 39.6 vs 94.0 ± 45.9; P\0.0001) and high hs-CRP (2.0 ± 1.5 vs 3.4 ± 1.9 mg/L; P\0.0001) than NGT\155 and similar to IGT and T2D. In addition, NGT C155 had a higher PWV and aortic hemodynamic parameters in comparison with NGT\155 and similar to IGT and diabetic patients. At multiple regression analysis, 1-h glucose resulted the major determinant of PWV, AP and AI in normotolerant, IGT and diabetic groups. In particular, 1-h glucose explained the 24.6% (P\0.0001), 6.7% (P=0.001), 26.7% (P\0.0001), 19.4% (P\0.0001) and 29.8% (P=0.011) of PWV variation, in whole study population, NGT\155, NGT[155, IGT and diabetic groups, respectively. The most clinically relevant information, from this study, is that there is a statistically significant and direct correlation between 1-h post-load plasma glucose and PWV in hypertensive patients, independently of other known risk cardiovascular factors. NGTC155 subjects, compared with NGT\155 subjects, have a higher PWV and its hemodynamic correlates similar to that of IGT and diabetic patients. In keeping with this, present data have allowed to identify a new early predictor of organ damage and emphasize the importance to perform an OGTT in all subjects with essential hypertension, paying attention not only to 2- h but also to 1-h post-load plasma glucose value, which is more strongly associated with arterial stiffness and other subclinical organ damage.

Horton’s disease. The importance of immediate diagnosis and treatment for better prognosis

S347 symptoms, the patient began to show a gradual improvement in overall clinical status. The case highlights the difficulty in making a rapid diagnosis of Horton’s disease and the efficacy of early steroid therapy in this vascular autoimmune disease that otherwise may result in irreversible functional and debilitating systemic damage.

Fig. 1

Fig. 2

M. Soldini*, D. Impallara, G. Cuozzo, F. Cerutti, F. Cruciani *Servizio distaccato di Medicina Interna e Cardiologia Dipartimento di Oftalmologia; Dipartimento di Oftalmologia Universita` ‘‘Sapienza’’, Roma, Italy

Initial signs of arterial occlusion with ischemic edema in the posterior pole and macular cherry-red in OD (Figure 1). Occlusion of the inferior-temporal branch superior-temporal and central retinal artery sparing the macular area in OS (Figure 2).

Giant cell arteritis (GCA) is a chronic and systemic inflammatory disease of the medium and large blood vessels. The early symptoms of this disease are nonspecific. The Authors describe a case of a 68 old patient suffering from Horton’s temporal arteritis or GCA, who came to our attention with a large and sudden visual loss due to occlusion of major retinal arteries, without other symptoms. The next day, for thorough investigations, the patient went to Day Hospital with a further worsening of the visual loss which required immediate admission to the ophthalmological ward that lasted 10 days. During the observation period it was hard to achieve an instant diagnosis due to the absence of clinical signs or diagnostic tests for Horton’s arteritis. Only after the third day of hospitalization when a corticosteroid therapy was undertaken for the appearance of significant systemic

References 1. Danesh-Meyer HV. Savino PJ. Giant cell arteritis. Curr Opin Ophthalmol. 2007 Nov;18(6):443–9 2. Fraser JA, Weyand CM, Newman NJ, Biousse V. The treatment of giant cell arteritis. Rev Neurol Dis. 2008 Summer;5(3):140–52 3. Kale N, Eggenberger E. Diagnosis and management of giant cell arteritis: a review. Curr Opin Ophthalmol. 2010 Nov;21(6):417–22 4. Schmidt WA, Moll A, Seifert A, Schicke B, Gromnica-Ihle E, Krause A. Prognosis of large-vessel giant cell arteritis. Rheumatology (Oxford). 2008 Sep;47(9):1406–8 5. Sciacca A, Di Giacomo V, Carmenini G. Le arteriopatie ad impronta flogistica. Edizioni Pozzi, Roma, 198 6. Soldini M, Gueli N, Toto A, Trua G, Carmenini G. L’interessamento cardiaco nella malattia di Horton. Ann Ital Med Int. 1987 JulSep;2(3):229–35.18

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S348 7. Vankalakunti M, Dharmanand BG, Chandra S, Pai SA. Giant cell arteritis: a clinical and pathological study. Natl Med J India. 2010 JanFeb;23(1):18-20

Statins for acute ischemic stroke A. Squizzato, E. Romualdi, F. Dentali, W. Ageno Research Center on Thromboembolic Disorders and Antithrombotic Therapies, Department of Clinical Medicine, University of Insubria, Varese, Italy Background: Statins have been claimed to be effective in the acute phase of ischemic stroke. The potential positive actions of statins during an acute cerebrovascular ischemic event are two-fold: a neuroprotective effect, limiting damage and improving recovery; and a preventative effect on early recurrence. Objectives: To quantify the potential benefits and harms of statins in the acute treatment of cerebrovascular ischemic events (both transient ischemic attacks (TIAs) and ischemic stroke). Search strategy: We searched the Cochrane Stroke Group’s Trials Register (November 2010); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 4); MEDLINE (1950 to November 2010); and EMBASE (1980 to November 2010). In an effort to identify further published, unpublished and ongoing trials we searched ongoing trials and research registers (November 2010), checked reference lists from relevant articles and contacted authors. Selection criteria: We included all randomized controlled trials (RCTs) comparing statins (any type and dosage) versus placebo or no treatment, administered within two weeks of the onset of acute ischemic stroke or TIA. Data collection and analysis: Two review authors independently selected studies for inclusion and extracted data. We assessed methodological quality and, when necessary, contacted study authors for additional data. We based quantitative analysis of outcome on the intention-to-treat principle. The primary outcomes were mortality from ischemic stroke and mortality from adverse drug effects, bleedings and infections. We estimated the overall treatment effect by the pooled odds ratio (OR) with 95% confidence interval (CI) using a fixed-effect model (Mantel–Haenszel). Main results: We included eight RCTs involving 625 participants. Only one study was judged as ‘low risk’ of bias. There were insufficient published data from the eight studies for all planned primary and secondary outcomes. No patients died from ischemic stroke or from adverse drug effects, bleeding or infections among the 444 participants in the six studies where these outcomes were reported. Statin treatment did not reduce all-cause mortality compared with placebo or no treatment (OR 1.51, 95% CI 0.60 to 3.81) in the 431 patients enrolled in seven studies. No cases of rhabdomyolysis (the breakdown of muscle fibres resulting in the release of muscle fibre contents (myoglobin) into the bloodstream) occurred in 274 patients enrolled in three studies. Authors’ conclusions: Insufficient data were available from randomized trials to establish if statins are safe and effective in cases of acute ischemic stroke and TIA.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Anamnesis: heart failure, chronic atrial fibrillation, hypertension. Domiciliary therapy: lanoxin 0.0625 mg, lasix 25 mg, fluxum 0.3 ml. Physical examination: Systolic heart murmur on aortic focus irradiated to the apex. Diffuse harsh breath. Laboratory tests: hyperglycaemia, hypertroponinemia (24.60 ng/ ml). We monitored troponin and myoglobin (as shown in table-1) and searched for ANA, ENA and Cytomegalovirus Antibodies (positive). Chest radiography: Increased pulmonary interstitial tissue. Cardiac silhouette enlargement. Chest computed tomography: Roundish opacity (26 mm) located in the postero-medial segment of the right lower lobe. Echocardiography: concentric hypertrophy of left ventriculus. Hypo-akinesia of the left ventriculus antero-lateral wall. Aortic, mitral and tricuspid regurgitation. ECG: atrial fibrillation. Non-ST elevation. During her stay in hospital the patient didn’t ever complain of chest pain, was treated with ASA i.v. and discharged with normal troponin value. Table 1

1st control 2nd control

Troponin ng/ml

Myoglobin ng/ml

n.v. (0.000-0.050)

n.v. (0.0-120.0)

24.60 50.00 a.m. 76.20 b.m.

rd

3 control

39.50

4th control

22.35

5th control

13.01

6th control

5.37

7th control

0.44

8th control

0.09

254.6

40.9

Table 2 Cytomegalovirus UA/ml

1st control 2

nd

control

IgG \ 0.4 (negative) [ 0.6 (positive)

IgM \ 15 (negative) [ 30 (positive)

73.40

31.20

72.40

37.30

Take back the ‘‘ultrasonograph ic stethoscope’’ Cytomegalovirus myocarditis with hypertroponinemia E. Stellitano, A. Nucera, B. Carerj, C. Caserta, F. Demetrio, P. Lipari, G. Meduri, A. Scordo, I. Tarzia, A. Stellitano*

N. Tarquinio, A. Balloni, W. Capeci, V. Catozzo, L. Falsetti1, A. Gentile, G. Rinaldi and F. Pellegrini

U.O. Medicina Interna P.O. Melito Porto Salvo (RC); *A.O.U. Policlinico ‘‘G Martino’’,U.O.C. Medicina Interna, Messime, Italy

Dipartimento di Medicina Interna ASUR ZT7 Ancona, Osp. ‘‘SS. Benvenuto e Rocco’’ Osimo 1Medicina Interna, Malattie ImmunoAllergiche e Res, Medicina d’Urgenza, Ospedale Torrette, Ancona, Italy

M.M. - female, 88 years old. Hospitalization because of fever, exhaustion, dyspnoea, feeling faint.

Background: Cardiovascular pathology represents one of the most prevalent disease in Internal Medicine departments; echocardiography

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 represents an essential method for its diagnosis and follow-up. Moreover, it is necessary for an internist to master ultrasonography in most of its various applications, being Internal Medicine departments in the center of the diagnostic process of most of the medical pathologies. Methods: For this reason our department programmed in the formative package of ASUR7, an echocardiography course; internists of different hospitals received yearly 92 h of theoretical-practical training. A certificate of attendance was released after overcoming a final examination. The course was done mainly bedside, focusing on the pathologies of the patients admitted to the Internal Medicine Department of the Osimo Hospital. Every session was guided by 3 expert tutors (one for patient) and 4 trainees for each tutor. Results: In two years 30 internists of our region (specialists coming from different hospitals or post graduate from the internal medicine school of the Marche Polytechnic University) got the ‘‘stethoscope of the third millennium’’ back in their hands. Conclusions: this experience can well represent not only the skill acquisition, but facilitates the Internist to holistic vision of patient and strengthens his diagnostic capacity.

Obesity and angiotensin type-1 receptors overexpression E.J. Tassone, I. Presta, D. Addesi, U. Gualtieri, F. Arturi, F. Perticone Department of Experimental and Clinical Medicine-University Magna Graecia of Catanzaro, Italy Obesity is an important risk factor for the development of multiple comorbidities and, above all, for the development of cardiovascular disease and type 2 diabetes (T2D). Obesity, especially the abdominal one, is associated with a pro-inflammatory condition. Adipokines may link obesity to its co-morbidities. In addition, renin-angiotensinaldosterone system (RAAS) may represent an important link between obesity and hypertension and T2D. In fact, there is evidence that angiotensin II (Ang II) could have an effect on glucose metabolism interfering with the insulin signaling cascade that leads to a reduced glucose uptake. The main effects of Ang II, such as vasoconstriction, aldosterone release, sodium and water reabsorption and blood pressure increase, are mediated by Ang II-type 1 receptors (AT1), even if their metabolic role remains unclear. In the present study we evaluated the differences existing between normotensive-normal weight (N-NW), hypertensive-normal weight (H-NW), normotensive-obese (N-OB) and hypertensive-obese (H-OB) subjects about the AT1 density (AT1d) on platelets, testing the hypothesis that the obesity is a condition in which the RAAS may be overexpressed. We enrolled 40 subjects, free from any pharmacological treatment, divided into 4 groups: N-NW, H-NW, N-OB and H-OB patients. BMI was calculated and the waist circumference (WC) was utilized as correlate of the distribution of visceral adipose tissue. Platelets were isolated and purified from venous blood samples and a binding assay with radiolabelled Ang II was performed to establish the amount of AT1 on platelets. AT1d progressively increases from N-NW group (5,2 9 103 cpm/100.000 PLT) to H-NW (6,2 9 103 cpm/100.000 PLT), N-OB (9,1 9 103 cpm/100.000 PLT) and H-OB (10,6 9 103 cpm/100.000 PLT) (p\0.0001). AT1d was significantly related with WC, BMI, insulin levels and estimated glomerular filtration rate. In a regression stepwise model, the only independent predictor of AT1d resulted the WC, that influences over 40% of its variation. Thus, we have observed that N-OB patients show the greatest AT1d than N-NW and the H-NM one. Of interest, the hypertensive condition, associated with obesity, increases only the 16% of AT1d. This evidence leads to suppose that the activation of RAAS, more evident in the obese subjects, is oriented to modify the insulin-sensitivity condition of

S349 these subjects, confirming the hypothesis that obesity is the major risk factor in the development of diabetes and cardiovascular events.

Autonomic cardiovascular effects of acute exposure to air pollution E. Tobaldini, M. Prado, E. Fiorelli, M. Pecis, S. Fossati, P. Carrer, N. Montano Department of Clinical Sciences, Internal Medicine II, L. Sacco Hospital, University of Milan, Milano, Italy In the last years, emerging literature has been focused on the link between air pollution exposure and cardiovascular morbidity and mortality. Indeed, some studies have shown that air pollution can worsen angina, exacerbate the exercise related ischemia in postmyocardial infarction patients, increase sudden cardiac deaths. The airborne particulate has been identified as a potential risk factor. However, despite this growing evidence, the etiopathogenetic mechanisms at the basis of this relation remain unclear. Aim of our study was to evaluate the effects of controlled exposure to air pollution on cardiac autonomic nervous system (ANS) through non-linear analysis of Heart Rate Variability (HRV) in a randomized, double blind and crossover study. We enrolled 6 healthy male subjects (age 25 ± 2.9, BMI 22,8 ± 3.3); all the subjects had a negative medical history for cardiovascular, respiratory or metabolic disease, they did not take any medication and they were non-smokers. The subjects went through two different randomized sessions: they underwent the inhalation of 1) filtered air mixture and 2) filtered air plus particulate mixture (PM 10, PM 2.5, PM 1.0 and PM 0.5), under a semi-closed oxygen tent. The mixtures have been furnished by SIAD (Societa` Italiana Acetilene e Derivati, Osio Sopra, Bergamo). During each session, we recorded ECG and respiration through a thoracic belt at baseline (T0), during 1 h exposure (T1) and two hours after the end of exposure (T2). HRV analysis was based on the assessment symbolic and entropy analyses on heart period and respiratory time series. Briefly, symbolic analysis is a non linear method based on the transformation of HRV series into a sequence of symbols (0, no variation and 1, variation), the construction of threebeats patterns, their grouping into families and finally the evaluation of the rates of occurrence of these families. Four families can be identified: 0 V%, marker of sympathetic modulation, 2UV%, marker of vagal modulation, 1 V% and 2LV%, of still unknown significance. The entropy measures quantify the complexity of a signal by the information analysis (larger the information, greater the complexity). We measured Conditional Entropy (CE), that quantifies the amount of information carried by a sample when the previous are known, i.e. smaller is the information and thus CE, the, higher the regularity and the predictability of the series. We extracted the time series of HRV and respiration, we chose time series of 250 ±50 beats length avoiding non-stationary segments and applied symbolic and entropy analysis to the selected samples. An ANOVA for repeated measure was used to assess statistical significance (p\0.05). The data showed no effects of the filtered air mixture on HRV in terms of symbolic and entropy measures during and after the exposition (T1 and T2) compared to T0. However, the inhalation of particulate induced significant changes in HRV at T2 with respect to T0. Symbolic analysis of heart period revealed a significant reduction of 2UV%, marker of parasympathetic modulation, from T0 to T2 (12,3 ± 5,4% vs 9.2 ± 3.9% respectively, p= 0.042). Conditional Entropy of the respiratory signals significantly increased from T0 to T2 (0.95 ± 0.15 vs 1.19 ± 0.16 respectively, p= 0.016). These results

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S350 were independent from respiratory frequency, that did not change after the exposition, as well as the carbon dioxide air levels, that remain constant during the experiments. These preliminary results suggested that the air particulate is able to acutely affect HRV, inducing a reduction of the parasympathetic modulation two hours after the exposure. In addition, the particulate seems to induce a modification of respiratory regulation, causing an increased complexity of respiratory control. In conclusion, these preliminary results suggest an acute effect of particulate on cardiac ANS, leading to the hypothesis that ANS could play an important role in the association between air pollution and increased cardiovascular risk.

Metabolic syndrome and target organ damage in an asymptomatic population at intermediate cardiovascular risk L.. Zocchi, F. Perego, F. Casella, M. Arquati, E. Renesto, G. Casazza, M. Cortellaro Department of Internal Medicine, Department of Clinical Science and Department of Medical Statistics and Biometry, ‘‘Luigi Sacco’’ Hospital, University of Milan, Milan, Italy Background: The value of the metabolic syndrome (MS) as a predictor of cardiovascular risk has been shown in a large number of observational studies. However it is not clear whether the metabolic syndrome is a distinct pathophysiologic entity or if it reflects an association of risk factors. It is still unclear which definition of MS is the best predictor of cardiovascular disease. Moreover the presence of subclinical target organ damage (TOD) in multiple vascular beds has been suggested as an indicator of overall atherosclerotic burden. Aims: to evaluate the association between MS and subclinical disease in multiple target organs and to evaluate which definition of MS better identifies TOD in asymptomatic people at intermediate cardiovascular risk. Methods: From March 2007 to July 2009 we examined 979 subjects at intermediate cardiovascular risk. We evaluated the presence of TOD in people with and without MS according to IDF and NCEP criteria. Considered variables in definition of MS were waist circumference, triglycerides, HDL cholesterol, systolic and diastolic blood pressure, and blood glucose. All the patients underwent assessment of common (non era misurata anche alla biforcazione e la ICA?) carotid intima-media thickness (cc-IMT), left ventricular mass index (LVMI), urine albumin to creatinine ratio (UACR), and anklebrachial index (ABI). Statistical analysis: Univariate and multiple logistic regression models were fitted to analyze the relations between MS and TOD. Results: in our population the NCEP criteria identified 338 individuals (34%), while IDF criteria identified 636 individuals (65%) as affected by MS; global concordance between IDF and NCEP was 65% (both positive 32%, n=316; both negative 33%, n=317). MS+ and MS- groups as defined by both criteria did not differ for baseline characteristics, except for variables included in the definitions of MS. Considering TODs, we found no correlation between having at least one TOD and being positive for MS with neither NCEP (MS- 63.1% Vs MS+ 66.5%; p=0.310) or IDF (MS- 60.8% Vs MS+ 66.0%; p=0.111) criteria. Considering specific TODs, increased UACR was significantly associated with MS diagnosed with both criteria (NCEP: MS- 12.2% Vs MS- 17.7%;p=0.017. IDF: MS- 10.6% Vs 16.0%;p=0.020), while only NCEP method identified subjects with cardiac damage (MS- 10.8% Vs MS+ 16.1%;p=0.020). There was no correlation between MS and TODs in other vascular beds. A multivariate logistic regression model was developed including age and sex to test the association between MS and TODs. MS diagnosed with NCEP and IDF criteria was associated with an 1,5-fold (CI=1.059 -

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 2.226; p\0.05) and a 1.6-fold increased UACR (CI=1.043 - 2.360; p\0.05) respectively. Only NCEP+ identified patients with a 1.6-fold increase of LVMI (CI=1.112 - 2.472; p\0.05). Still, we found no correlation between MS and having at least one TOD with both criteria. To test if MS predicted the presence of TODs better than the single risk factors included in the definition, we developed a second multivariate logistic regression model including age, sex, waist circumference, triglycerides, HDL cholesterol, blood pressure and blood glucose levels. According to NCEP or IDF criteria we observed no correlation between MS+ and having at least one TOD. Considering specific vascular districts, the observed associations with kidney and cardiac damage disappeared, due to the contribution of well known risk factors such as age, blood pressure and blood glucose levels. Conclusion: in an asymptomatic population at intermediate cardiovascular risk, MS+ diagnosed with NCEP or IDF criteria was significantly associated with glomerular endothelial dysfunction (UACR). On the contrary only NCEP+ identified patients with cardiac damage. However MS criteria did not predict the presence of TODs better than the classic risk factors included in the definitions.

Metabolism, diabetes and clinical nutrition Use of saxagliptin in diabetes mellitus type 2 patients A. Asti, A. D’Alessandro, C. Cristiano, G. D’Alessandro, G. Perrone, L. Viscardi, P. Bellis U.O.C. Medicina Interna P.O.’’S. Maria di Loreto Nuovo’’ A.S.L. NA/1, Napoli, Italy Saxagliptin is an oral hypoglycemic, specifically it is a DPP-4 inhibitor used in association with metformin, thiazolidinediones, and sulfonylurea in not compensated diabetes mellitus type 2 patients. We recruited 32 patients (15 M and 17 F), mean age 67,3 years (± 10,2), affected by diabetes mellitus type 2, already taking metformin, thiazolidinediones or sulfonylurea, however with glycated Hb[ 7,5% and FPG [ 140 mg/dl. We estimated some metabolic and anthropometric parameters at time 0’ and then we added saxaglyptin 5 mg/die. According the AIFA rules, we made the follow up after 4 months and we evaluated the same parameters. We have noticed a decrease of FPG, from 191 mg/dl to 160 mg/dl (p\ 0,0001), of glycate Hb, from 8,1% to 7,5% (p\0,0001), of weight, from 76,5 kg to 74,4 kg (p\0,0001), of BMI from 28 to 27,5 (p\0,0003), and of abdominal circumference, from 92,5 cm to 90,8 cm (p\0,0001). We also recorded a reduction of total cholesterol, from 198 mg/dl to 179 mg/dl (p\0,0001), of LDL cholesterol, from 122 mg/dl to 112 mg/dl (p\0,0002), and of triglycerides, from 178 mg/dl to 154 mg/dl (p\0,0003), without significant change of HDL cholesterol, transaminase and pancreatic amylase. There were not severe side effects, only a patient had a transient headache for the first 15 days and another patient had some episodes of morning nausea. Nobody suspended the therapy. Our results confirm the international literature date, saxaglyptin is effective in association with other oral hypoglycemic drugs in not compensated diabetes mellitus type 2 patients and it has a good impact on lipid pattern too.

Use of liraglutide in diabetes mellitus type 2 patients A. Asti, A. D’Alessandro, C. Cristiano, G. D’Alessandro, L. Viscardi, G. Maresca, P. Bellis U.O.C. Medicina Interna P.O.’’S. Maria di Loreto Nuovo’’ A.S.L. NA/1, Napoli, Italy

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Liraglutide is an analogous of the human GLP-1 used in not compensated diabetes mellitus type 2 patients already taking oral hypoglicemic. This drug reduces the hepatic gluconeogenesis and it induces the release of insulin from the pancreatic beta-cells, using a glucose-dependent mechanism. We studied 11 patients (5 M and 6 F), mean age 65,3 years (SD ± 10,9) in treatment with Metformin or Thiazolidinediones from 3,9 years (±2,6), who have a glycate Hb[7.5% and FPG\140 mg/dl. We detected some anthropometric and metabolic parameters at time 0’, then we added to background therapy liraglutide 0,6 mg/day before the lunch and after 7 days we increased the dose to 1,2 mg/day. According the AIFA rules, we made the follow-up after 4 months. The results have showed a decrease of FPG, from 207 mg/dl to 191 mg/dl (p\0.00019), of glycate Hb, from 8,9% to 7,7% (p=0.001), of weight, from 92 to 88,8 kg (p=0.0004), and of the abdominal circumference, from 102 to 98,5 (p=0.01). Moreover we detected a reduction of total cholesterol, from 210 mg/dl to 191 mg/dl (p=0,001), and of triglycerides, from 197 to 166 mg/dl (p=0,001), while the increase of HDL cholesterol and the reduction of LDL cholesterol were not significant. The changes of transaminase and amylase were not relevant too. In only one case we had to stop the therapy for persistent nausea and vomit. In other cases these symptoms had disappeared during the first 10 days of therapy. According our results liraglutide can be considered in the therapy of not compensated diabetes 2 patients in association with other oral hypoglycaemic, especially in obese patients.

Does intervention on glycemic control influence HDL cholesterol levels in type 2 diabetes? A pilot study G. Barbarossa, A. Renzi, L. D’erasmo, C. Favoccia, A. Gallo, S. Morano, M. SantillI, A. MontalI, D. PergolinI, A. Gatti, E. Ciociola, M. Rossetti, M. Fallarino, A. Carnovale, E. Mandosi, M. Arca, S. Filetti, M. Maranghi Dipartimento di Medicina Interna e Specialita` Mediche- Policlinico Umberto I, Universita` di Roma Sapienza, Roma, Italy Background and Aims: HDL cholesterol (HDL-C) levels are strongly and inversely associated with coronary heart disease. Low HDL-C is the hallmark of atherogenic dyslipidemia in type 2 diabetic patients. To date, an optimal treatment able to both raise HDL-C levels and enhance its atheroprotective functions is still lacking. Previous studies have shown an inverse relationship between HDL-C levels and glycemic control. The aim of our study is to assess if the achievement of a better glycemic control could lead to an improvement in HDL-C levels in patients with type 2 diabetes not on lipid lowering therapy. Materials and Methods: Seventy-three diabetic patients with no medical history of cardiovascular events were studied: 36 subjects with HbA1c = [7% (cases) and 37 subjects with HbA1c levels\ 7% (controls). In the case-group a six months intervention with insulin or metformin or sulfonylurea was started in order to reduce HbA1c values. Anthropometric parameters, glycemic and lipid levels were measured at baseline and after 6 months for all patients. Changes between 6 months and baseline values were measured for all variables analyzed. Data are expressed as median and interquartile ranges. Wilcoxon-Mann–Whitney test and Spearman correlation analysis were performed to compare groups and to correlate HbA1c and HDL-C changes. A p value of\0.05 was considered significant. Results: After 6 months HbA1c was significantly improved in cases but not in controls (HbA1c change - 0.6 (-1.7-0.0) in cases vs - 0.1(-0.2-0.3) in controls; p \ 0.001). No significant changes in BMI, total cholesterol, triglycerides and HDL-C levels were observed between the two groups. A significant

S351 inverse correlation between HbA1c and HDL-C changes was found in cases but not in controls (rho - 0.331; p = 0.049 in cases and rho 0.93; p= 0.58 in controls). Furthermore, by stratifying the diabetic population according to HbA1c improvement, we found a significant inverse correlation between HbA1c and HDL-C changes in casepatients with improved glycemic control (rho - 0.45; p = 0.024). Conclusion: In our population changes in HbA1c and HDL-C were inversely correlated in patients with poor glycemic control. Further studied are needed in order to understand if improvement of HbA1c could have a positive effect on HDL-C levels and functions.

Incretin axis and alpha cell function in metabolic syndrome S. Calanna, F. Urbano, Di Pino Antonino, Privitera Graziella, Tomaselli Tania, Zagami Rose Maria, A.M. Rabuazzo, F. Purrello Dipartimento di Biomedicina Clinica e Molecolare di Catania, Catania, Italy Objective: In type 2 diabetes the incretin plasma levels and/or biological activity have been shown to be reduced and plasma glucagon (the major hyperglycemic hormone) concentrations are higher and fail to decrease appropriately in response to meals. These alterations are present even in pre- diabetic conditions, like impaired glucose tolerance state. The present study was undertaken to investigate the entero-insular axis and the alpha cell function in subjects with metabolic syndrome, a condition at high risk for diabetes. Research design and Methods: Using oral glucose tolerance test (OGTT) we studied incretin levels and alpha cell function in 96 obese subjects with normal fasting glucose, with (n=29) and without MS (n=67) Results: Normotolerant MS+ individuals showed, in comparison to MS-, higher GIP levels at 30’ (321 ± 47 vs 220 ± 21, p=0,03), at 60’(296 ± 42 vs 193 ± 18, p=0,01)), at 90’ (292 ± 36 vs 184 ± 15, p=0,003) and at 120’ (292 ± 36 vs 182 ± 17, p=0,004) during the OGTT and consequently higher AUC (0-120) for GIP (33119 ± 4357 vs 21536 ± 1787, p=0,007). In contrast there were no differences in kinetics and in GLP-1 plasma levels and accordingly in AUC (0-120) for GLP-1. In MS+ glucagon plasma levels were higher during the entire profile of OGTT, although not significant (at basal 85 ± 11 vs 67 ± 3 pg/ml, p=0.1). Furthermore MS+ individuals showed a delayed glucagon suppression reaching 28% and 71% of maximum glucagon suppression respectively at 30’ and at 60’ of OGTT in comparison to 81% and 100% in MS- group at the same times. Conclusion: Our data show that NGT subjects with metabolic syndrome have increased plasma GIP levels and a delayed glucagon suppression after the oral glucose load. These features have been observed in type 2 diabetes and described as a mechanism by which the diabetic subjects attempt to compensate for their reduced insulinotropic effect of GIP. Since GIP has been shown to enhance alpha cell secretion, our data suggest that in subjects with metabolic syndrome there is an early abnormality of the entero- insular axis that could be responsible for the delayed glucagon suppression during the OGTT, an early marker of altered glucose tolerance.

Low circulating vitamin E in patients with the metabolic syndrome: role of oxidative stress E. Catasca, L. Napoleone, F. Angelico, R. Carnevale, C. Calabrese, D. Pastori, L. Perri, V. Raparelli, T. Augelletti, P. Pignatelli, S. Basili, R. Cangemi Divisione I Clinica Medica, ‘‘Sapienza’’ University of Rome, Rome, Italy

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S352 Background and Aims: People with the metabolic syndrome are at increased risk of coronary heart disease and other diseases related to plaque buildups being associated with an accelerated atherosclerosis. Oxidative stress is believed to play a crucial role in atherosclerotic process. Vitamin E is a powerful chain-breaking antioxidant, which may be a protective factor against oxidative stress-related diseases. We planned this study to evaluate the behavior of vitamin E in patients with metabolic syndrome and its relationship with oxidative stress, measured by serum 8-hydroxy-2-deoxyguanosine. Methods and Results: In 92 cases (with 3 or more risk factors defining the syndrome) we found lower vitamin E/cholesterol ratio and higher serum 8-OHdG compared to those observed in 80 controls (with less than 3 risk factors) (p\0.001). These parameters gradually decreased and increased, respectively, by increasing the number of metabolic syndrome components (p\0.001). Thus, an adjusted multiple regression analysis showed that serum 8-OHdG was the only independent predictor of vitamin E/cholesterol ratio. Conclusion: This study shows that MS patients have low vitamin E/cholesterol ratio. This change is likely to reflect enhanced oxidative stress and may provide further insight in the mechanisms accounting for the accelerated atherosclerosis in patients with metabolic syndrome.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 p=0.026). Finally, serum uric acid concentrations directly correlated with body-weight (r=0.455, p=0.046), Body Mass Index (r=0.566, p=0.009), fasting insulinemia (r=0.589, p=0.008) and HOMA-IR (r=0.563, p=0.012) in MS women. Discussion: the current study clearly demonstrates that MS women have lower serum vitamin D levels than healthy control women. Vitamin D levels in MS patients were independent in bone-related parameters, thereby suggesting that relative hypovitaminosis D is not a consequence of an altered bone metabolism but is directly related to MS. Concordantly, vitamin D levels decreased with age in controls but not in MS patients. In addition, circulating vitamin D levels directly correlated with LDL-cholesterol; an explanation for this effect is a vitamin D action on intestinal calcium channels. As is known MS also includes the presence of a low grade inflammatory state: in agreement in MS women levels of CRP and uric acid are higher than control group. In particular uric acid levels directly correlate with weight, Body Mass Index, basal insulinemia and HOMA-IR suggesting its possible role in MS pathogenesis. In conclusion, our results suggest that vitamin D levels are lower in women with MS, so the opportunity of a treatment with vitamin D.

Vitamin D levels in metabolic syndrome

Glutamine favours weight loss in obese, non-dieting female patients: A pilot study

S. Ciarla, M. Struglia, P. Giorgini, F. Pantoli, R. Del Pinto, G. Properzi, C. Ferri

C. Conte, A. Molfino, M.T. Lacaria, I. Preziosa, A. Mari, A. Laviano, F. Rossi Fanelli

Division and School of Internal Medicine, University of L’Aquila, San Salvatore Hospital, L’Aquila, Italy

Department of Clinical Medicine, Sapienza University, Roma, Italy

Introduction: metabolic syndrome (MS) is commonly defined as the cluster of glucose metabolism abnormalities, central adipose tissue accumulation, lipid pattern and blood pressure profile and is combined to an increased cardiovascular risk. Some findings also suggest that individuals, particulary among the female gender, with MS have low circulating levels of vitamin D compared to subjects without MS. Due to the suggested correlation between low vitamin D levels and cardiovascular risk, this might further increase cardiovascular risk in MS patients. Aim of the study: to further investigate the relationship between MS and vitamin D in the female gender. Methods: Anthropometric parameters, blood pressure, serum lipid and glucose levels were evaluated in 43 MS women (45.92 ± 11.58 years) MS diagnosis made according to the Adult Treatment Panel III (ATP-III) criteria, without any concomitant conditions or medications known to interfere with vitamin D metabolism. Bone metabolism was assessed in these women by wellrecognized parameters. Circulating dihydroxyvitamin D, fasting insulin, C-reactive protein (CRP) and uric acid concentration were also assessed. The Homeostatic Model Assessment Insulin Resistance (HOMA-IR) was used to calculate insulin resistance. All of the above variables were also measured in 40 healthy age-matched women. Results: MS women had lower levels of vitamin D than control women (11.61 ± 6.84 ng/ml vs 39.41 ± 25.91 ng/ml, p \0.001) but similar levels of serum calcium (9.02 ± 0.55 mg/dl vs 9.08 ± 0.40 mg/dl), alkaline phosphatase (165.28 ± 46.62 UI/l vs 137.10 ± 41.25 UI/l) and parathyroid hormone (51.31 ± 19.71 pg/ ml vs 55.19 ± 28.11 pg/ml). MS women had higher serum levels of CRP (0.74 ± 0.20 mg/dl vs 0.16 ± 0.07 mg/dl, p\0.02) and uric acid (5.33 ± 0.40 mg/dl vs 3.78 ± 0.44 mg/dl, p\0.001) than controls. Circulating vitamin D levels inversely correlated with age in the control group (r= -0.601, p=0.005) while directly correlated with serum LDL-cholesterol concentrations in MS women (r=0.455,

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Background: Glutamine has been demonstrated to enhance glucose metabolism in critically ill patients resulting in better clinical outcome. Recent experimental data indicate that glutamine supplementation prevents fat accumulation and body weight gain in animals fed with a high fat diet. It is therefore tempting to speculate that glutamine supplementation may favor body weight loss and enhance glucose metabolism in obese patients. Methods: after giving informed consent, female obese non-diabetic patients (BMI[30) were considered for a cross-over, placebo controlled trial. Patients were randomly allocated to receive a supplementation of either 0.3 g/Kg BW/day of glutamine(Addamin G, Nutricia Italia) or an isonitrogenous protein supplement (Protifar, Nutricia Italia) for 4 weeks. Then, after a 1-week wash out period, patients previously supplemented with glutamine received the protein supplement and viceversa for 4 more weeks. Patients were asked to maintain their usual eating habits and lifestyle. Body weight (kg), waist circumference (cm), fasting glucose (mg/dL) and insulin (IU/ mL) levels were assessed at the end of each 4-week period. Data were statistically analyzed using the Student’s t-test and are presented as mean ± SD. Results: 6 female obese patients (age: 40.8 ± 15.3 yrs; BMI: 32.4 ± 3.2) were enrolled. After glutamine supplementation, body weight significantly declined (pre: 85.0 ± 10.4; post: 82.2 ± 10.1; p\0.01), while it did not change after protein supplementation (pre: 83.2 ± 9.1; post: 82.4 ± 8.8; p=n.s.). Glutamine supplementation reduced waist circumference (pre: 102.7 ± 2.0; post: 98.9 ± 2.9; p=0.01), whereas protein supplementation had no effect (pre: 100.8 ± 1.0; post: 100 ± 2.0; p=n.s.). Glucose levels did not change significantly after either glutamine or protein supplementation (glutamine: 87.4 ± 9.3 vs 89 ± 1.5, p=n.s.: protein: 90 ± 8.4 vs 89.8 ± 9.7; p=n.s.). Insulin levels did not change significantly after either glutamine or protein supplementation (glutamine: 9.8 ± 4.3 vs 8.3 ± 3.5, p=n.s.: protein: 7.8 ± 3.7 vs 7.8 ± 1.9; p=n.s.), although glutamine reduced insulin levels by 15%.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Discussion: data obtained in the present pilot study show that glutamine supplementation in obese non-diabetic female patients promote weight loss even in the absence of a prescribed hypocaloric diet. Although glutamine supplementation did reduce insulin levels by 15%, this achievement did not reach statistical evidence, probably because the population studied was numerically limited and did not present with impaired glucose metabolism. These preliminary results suggest that glutamine supplementation can be considered as an adjunct treatment of obese patients. More studies are needed to confirm these data and assess the role of glutamine in improving deranged glucose metabolism.

Different pattern of early vascular injuries markers according to metabolic syndrome or insulin resistance A. Di Pino, G. Privitera, T. Tomaselli, S. Calanna, L. Spadaro, M.A. Rabuazzo, F. Purrello U.O.C. of Internal Medicine, Department Clinical and Molecular Biomedicine, University of Catania, Hosp. Garibaldi-Nesima, Catania, Italy Objective: Obese individuals present different cardiovascular risk depending on several conditions such as metabolic syndrome (MS) and insulin-resistance level. There are increasing evidences that insulin-sensitive sub-phenotypes (metabolically health obese, MHO) presents a favourable cardiovascular risk profile compared to obese insulin-resistant subjects (unhealthy obesity). Methods: We studied 132 obese subjects divided in two groups by the presence or absence of MS, and furthermore classified in unhealthy and healthy obesity according to insulin resistance (HOMA-IR[2.5). We measured Intima-media thickness (IMT), assessed by carotid ultrasound, and PWA evaluated using SpygmoCor. In particular, we calculated Augmentation Pressure, a measure of the contribution of the early reflected wave to central systolic pressure, Augmentation index (AIx), defined as AP divided by central pulse pressure and expressed as a percentage, and SEVR, an estimate of myocardial perfusion. Results: In MS IMT was significantly higher (1.5 ± 0.7 mm vs 1.1 ± 0.6, p\0.05); SEVR was significantly reduced (149 ± 26.9 vs 159.9 ± 31.7%, p\0.05). Augmentation Pressure (AP) was higher, but latter not significantly (10.9 ± 5.8 vs 8.4 ± 5.5 mmHg p\0.05) compared to non MS. When data were analyzed according to healthy or unhealthy obesity definition, IMT values were similar in both groups (1.2 ± 0.7 vs 1.3 ± 0.6 mm p=ns). In unhealthy obese PWA resulted in increase of AP (7.4 ± 6 vs 9.6 ± 6.1 mmHg) and AI (20.5 ± 14.5 vs 25.1 ± 11.7) compared to MHO, although these differences were not significant. SEVR values were similar in both groups (153 ± 42.4 vs 150.7 ± 24.9%) Conclusion: Our findings suggest that MS definition is able to better identify early vascular abnormality in obese individuals.

A home-based programme of aerobic physical exercise exerts metabolic and anti-inflammatory properties reversing metabolic syndrome D. Di Raimondo, A. Tuttolomondo*, A. Casuccio**, C. Butta`, G. Licata*, A. Pinto U.O.C. Medicina Vascolare; * U.O.C. di Medicina Interna e Cardioangiologia; ** U.O.C. di Oculistica, Universita` degli Studi di Palermo, Palermo, Italy Introduction and Aim: It is well established that physically fit individuals have a reduced risk of developing CVD (cardiovascular

S353 disease) and other age-related chronic disorders [1]. Regular exercise is an established therapeutic intervention with an enormous range of benefits, including reduction of mortality and morbidity of atherosclerotic patients, colon cancer, and breast cancer, ischemic heart disease, heart failure and type 2 diabetes. Subclinical inflammation in polymetabolic patient has been recently found by many authors. Insulin resistance, a key player in the pathogenesis of the metabolic syndrome (MS), has been increasingly recognized as having an important role in inflammatory pathways. Regular physical activity clearly demonstrated to provide various anti-inflammatory actions assessed by various authors in different populations. Despite of these clear benefits, many patients are unable to attain long-term results through chronic physical activity for different causes: first of all the presence of co-morbidities, but also in patients in which exercise prescription is theoretically possible we observe the loss of patient due to lack of facilities, lack of motivation, or perception of too hard training. On this basis aim of our study was to assess effects of a home based programme of fast walking on some metabolic parameters and on systemic inflammation markers in patients affected by metabolic syndrome (MS) assessed by ATP III criteria [3]. Materials and Method: We enrolled 176 subjects (95 men and 81 women, mean age 57, 8 ± 13,46 years). Main inclusion criterion was the presence of at least three findings of metabolic syndrome as stated by ATP III criteria [3]. Patients were provided of an OMRON step counter type Walking Style II, that provides data about total number of steps, total number of aerobic steps, total distance walked, total aerobic distance walked, total energy expenditure (calories). Patients were invited to walk for one hour every day. The walking velocity was required higher than the one retained ‘‘comfortable’’ by the patient, previously assessed in the runin visit. Walking velocity during training period was obtained analyzing the separate aerobic distance covered recorded by step counter and comparing it with the time spent walking aerobically as reported in the patient’s diary. Weekly, during the periodic control of data, patients enrolled were required to modify walking velocity and/or walking distance to adhere the protocol. Before and after the end of the 24 weeks of intervention anthropometric data and laboratoristic determination were executed. Results: After the 24 weeks of intervention BMI changed from 31,59 to 29,23 (p \ 0.001); mean waist circumference passed from 105,19 to 100,06 cm (p\0.001); mean fasting glucose changed from 119,76 to 114,32 mg/dl (p \ 0.001); for diabetic population (n: 70) mean glicated haemoglobin levels changed from 7.58 to 6,86% (p\0.001); total cholesterol levels from 192,15 to 185,78 mg/dl (p \ 0.001); HDL cholesterol levels raised significantly from 43,03 to 45,63 mg/dl (p\0.001); triglycerides levels lowered from 148,29 to 135,20 mg/dl (p \ 0.001); WBC changed from 7.361,08 to 7.022, 56/mm3 (p \ 0.001); hsCRP from 0,548 to 0,280 mg/dl (p \ 0.001); fibrinogen serum levels lowered from 339,68 to 314,86 mg/dl. Before of the training period we had 110 patient with three SM findings, 50 patients with 4 findings and 16 with all the five findings of MS. After the intervention the recalculation of the criteria showed that 12 patients had all the five findings, 24 had 4 elements, 84 had three elements. The other part of population at the end of the study were lacking in the ATP III criteria, having two findings (49 subjects), one finding (6 subjects) or 0 findings (one subject). In conclusion, a home-based programme of aerobic physical activity improves metabolic asset and systemic inflammatory markers and reverses MS. References 1. Blair SN, Cheng Y, and Holder JS. Is physical activity or physical fitness more important in defining health benefits? Med Sci Sports Exerc. 2001;33:S379–S399 2. Festa A, D’Agostino R Jr, Howard G, et al. Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation. 2000;102:42–7 3. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection,

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S354 Evaluation, and Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001 May 16;285(19):2486-97

Using hemoglobin A1C to define the metabolic syndrome in a cohort of Italian nondiabetic caucasians T.V. Fiorentino, V. Caruso, F. Iorio, A. Grembiale, E. Succurro, F. Andreozzi, F. Arturi, F. Perticone, G. Sesti Department of Experimental and Clinical Medicine, University ‘‘Magna-Græcia’’ of Catanzaro, Catanzaro, Italy Background: The metabolic syndrome is a condition characterized by a clustering of metabolic and atherosclerotic risk factors including visceral adiposity, dyslipidemia, hypertension, and hyperglycemia. The metabolic syndrome is associated with an increased risk for both type 2 diabetes and cardiovascular disease. In 2010, the American Diabetes Association (ADA) has revised the criteria for the diagnosis of type 2 diabetes and the categories at increased risk for diabetes including impaired fasting glucose (IFG), and recommending hemoglobin A1C (A1C) measurements as another diagnostic test option in addition to fasting plasma glucose (FPG) values. Specifically for the categories of increased risk for type 2 diabetes, the new ADA recommendations state that an A1C from 5.7 to 6.4% identifies individuals at high risk for diabetes; to whom the term pre-diabetes may be applied. Aims: In the present study, we evaluated whether A1C values can be used instead of FPG to identify subjects with metabolic syndrome in a well characterized sample of nondiabetic Caucasians. Additionally, we determined the diagnostic accuracy of the metabolic syndrome definition using HbA1c in identifying insulin-resistant subjects. Methods: The cardiometabolic risk factors, HbA1c, and glucose tolerance were analyzed in 774 nondiabetic white subjects participating to the CATAnzaro MEtabolic RIsk factors Study (CATAMERIS), a cross-sectional study. The inclusion criteria were: age [20 years, absence of diabetes mellitus, defined as A1C [6.5%, FPG [126 mg/dl or 2-h post-load plasma glucose [200 mg/dl, and presence of one or more cardio-metabolic risk factors including elevated blood pressure, dyslipidemia, overweight/obesity, and family history for diabetes. On the first day, after 12-h fasting, subjects underwent anthropometrical evaluation, including body mass index, and waist circumference, and a venous blood sample was drawn for laboratory determinations. On the second day, after a 12-h fasting, a 75 g oral glucose tolerance test was performed with sampling for plasma glucose and insulin. Insulin sensitivity was estimated with an oral glucose tolerance test-derived insulin sensitivity index. Insulin resistance was defined as the lower quartile of insulin sensitivity index. Results: A 90.9% agreement existed between the use of HbA1c and the FPG for diagnosis of the metabolic syndrome ( j coefficient = 0.813); however, the proportion of subjects who met the metabolic syndrome criteria using the HbA1c was greater (42.1 vs. 39.7%). Compared to the subjects who met the metabolic syndrome criteria using the FPG alone, those with the metabolic syndrome using the HbA1c-alone criterion were younger, had greater visceral adiposity, greater levels of inflammatory markers and liver enzymes, and lower blood pressure. Next, we evaluated the diagnostic property of HbA1c and FPG to identify insulin-resistant subjects (lowest ISI quartile) by calculating a ROC curve. The area under the ROC curve of FPG for identifying insulin-resistant subjects was 0.771 (95% CI 0.739–0.800). The area under the ROC curve of HbA1c for identifying insulin resistant subjects was 0.648 (95% CI 0.613–0.681). The difference between the 2 areas under the ROC curve (0.123, 95% CI 0.0700–0.176) was statistically significant (p = 0.0001). The

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 relatively low sensitivity of the HbA1c criterion for identifying subjects with insulin resistance might indicate that a significant number of subjects who were insulin resistant but were not considered to have the metabolic syndrome. Insulin-resistant subjects who did not meet the criteria for the metabolic syndrome using the HbA1c had an unfavorable cardiovascular disease risk profile. Conclusion: In conclusion, although a good agreement existed between the HbA1c and FPG criteria for the diagnosis of the metabolic syndrome, appreciably different groups of subjects were classified using each method. These data indicate that the metabolic syndrome using the HbA1c criterion would fail to identify a significant number of insulin-resistant subjects at an increased risk of diabetes and cardiovascular disease.

Association of C3 with clinical features of the metabolic syndrome and different measures of insulin resistance A. Grembiale, F. Ursini, S. Cufone, M. Ruffo, E. Pedace, S. Mastroianni, V. Caruso, E. Succurro, F. Arturi Department of Experimental and Clinical Medicine, University ‘‘Magna-Græcia’’ of Catanzaro, Catanzaro, Italy Introduction: Metabolic syndrome is a complex condition characterized by a cluster of cardiometabolic risk factors and associated with an increased risk of developing type 2 diabetes and atherosclerotic cardiovascular disease. Growing evidences suggest that metabolic syndrome is associated with a low-grade inflammatory state and an increase in circulating inflammatory markers. Complement C3 is the major plasma protein of the immune system complement pathway, and its synthesis is increased in response to inflammation and infection. C3 have shown significant correlation with obesity, and high gene expression of C3 has been demonstrated in omental adipose tissue in obese patients. C3 levels are also independently associated with the risk of myocardial infarction in male patients. The aim of this study was to study plasma C3 levels in a cohort of adult subjects and evaluate the association of C3 with cardiometabolic risk factors characterizing metabolic syndrome. Methods: All 839 subjects participating in the study were Caucasian. Subjects were excluded if they had chronic infectious diseases, history of any malignant disease, history of alcohol or drug abuse, liver or kidney failure or rheumatic disorders. Weight, height, waist circumference and blood pressure were measured. A 75-g oral glucose tolerance test was performed in subjects not known to have diabetes. Measurements of carotid IMT were obtained. Insulin resistance was estimated with 15 different surrogate measures: fasting plasma insulin, 2-hour plasma insulin, fasting plasma C-peptide, HOMA-IR, log 1/HOMA-IR, ISI 00 , ISI 1200 , I0/G0, QUICKI, FIRI, McAuley index, Raynaud index, Bennetts index, Matsuda index, Avignon index. In 62 patients insulin sensitivity was assessed also by euglycemic-hyperinsulinemic clamp. Results: C3 levels were significantly higher in ATP-III metabolic syndrome patients (1.26 ± 0.24 g/L) compared to patients that not satisfied criteria for diagnosis of metabolic syndrome (1.16 ± 0.25 g/L, P \ 0.0001). In univariate analysis C3 levels were positively correlated with BMI (R = 0.29, P \ 0.0001), waist circumference (R = 0.23, P \ 0.0001), systolic blood pressure (R = 0.09, P = 0.006), total cholesterol (R = 0.08, P = 0.02), triglyceride (R = 0.26, P \ 0.0001), fasting plasma glucose (R = 0.10, P = 0.002), 2 hour plasma glucose (R = 0.13, P = 0.005), fasting plasma insulin (R = 0.16, P \ 0.0001), 2 hour plasma insulin (R = 0.18, P = 0.003), HOMA-IR (R = 0.17, P \ 0.0001), C-reactive protein (R = 0.32, P \ 0.0001) and negatively correlated with HDL-cholesterol (R = -0.10, P = 0.003) and Matsuda index (R = -0.21,

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 P = 0.0004). In a multiple regression model containing age, sex, BMI, systolic blood pressure, fasting plasma glucose, HDL-cholesterol, triglycerides and HOMA-IR, C3 was independently associated with BMI (Beta* 0.15, P \ 0.0001), HDL-cholesterol (Beta* -0.14, P = 0.001), triglyceride (Beta* 0.09, P = 0.1) and HOMA-IR (Beta* 0.10, P = 0.01).In univariable analysis C3 was positively correlated with fasting plasma insulin, 2-hour plasma insulin, fasting plasma C-peptide, I0/G0, HOMA-IR, FIRI, and negatively correlated with ISI 00 , ISI 1200 , QUICKI, McAuley Index, Raynaud, Bennett, Log 1/HOMA, Matsuda, Avignon. The strongest correlation was observed with McAuley Index. In 62 patients we performed also euglycemichyperinsulinemic clamp, and after correction for age and sex, C3 levels were negatively correlated (R = -0.15, P = 0.02) with glucose metabolized during clamp (M). Conclusion: Serum C3 levels are higher in metabolic syndrome patients compared to age- and sex-matched healthy controls. C3 levels are strongly correlated with different features of metabolic syndrome, including BMI, waist circumference, systolic blood pressure, total and HDL cholesterol, triglyceride, fasting plasma glucose, 2 hour plasma glucose, fasting plasma insulin, 2 hour plasma insulin, C-reactive protein. In addition, C3 was also correlated with different measures of insulin resistance, such as fasting plasma insulin, 2-hour plasma insulin, fasting plasma C-peptide, I0/G0, HOMA-IR, FIRI, and negatively correlated with ISI 00 , ISI 1200 , QUICKI, McAuley Index, Raynaud, Bennett, Log 1/HOMA, Matsuda, Avignon and glucose metabolized during clamp (M).

S355 Table continued Peripheral onset (P) Bulbar onset (B) PEG placement from diagnosis, days (m ± SD; range)

920 ± 650 (150–2035)

600 ± 490 (30–1460) (p = ns)

At diagnosis

74 ± 14

67 ± 10

At time of PEG placement

62 ± 11 (p = 0.00 55 ± 10 (p = 0.00 vs. weight at vs. weight at diagnosis) diagnosis)

After 1 year of HEN

64 ± 11 (p = ns vs. time of PEG placement)

57 ± 8 (p = ns vs. time of PEG placement)

At time of diagnosis

25 ± 3

24 ± 3

At time of PEG placement (±sd)

22 ± 3 (p = 0.00 vs. BMI at diagnosis)

21 ± 4 (p = 0.01 vs. BMI at diagnosis)

After 1 year of HEN (±sd)

21 ± 3 (*p = ns vs. time of PEG placement)

21 ± 3 (*p = ns vs. time of PEG placement)

Weight, kg (m ± SD)

BMI (m ± SD)

% of weight loss at time 14 ± 8 of PEG placement from diagnosis

15 ± 12 (p = ns vs. P)

Home enteral nutrition (HEN) can maintain weight and body mass index (BMI) in amyotrophic lateral sclerosis (ALS) patients I. Kushta, M. Muscaritoli, S. Lucia, A. Molfino, A. Canelli, F. Rossi Fanelli Dipartimento di Medicina Clinica, Sapienza Universita` di Roma, Roma, Italy Introduction: Amyotrophic lateral sclerosis (ALS) is an incurable fatal motoneuron disease, characterized by progressive weakness, muscle wasting and death ensuing 3–5 years after diagnosis (1). Compromised nutrition leading to weight loss is a common and significant problem in ALS patients resulting in significant negative prognostic indices to survival (2–4). Home Enteral Nutrition via PEG is the choice to provide long term nutritional support in order to maintain or restore weight and BMI. Materials and Methods: We retrospectively analyzed 47 (26 M, 21 F) ALS patients, who had completed a follow-up period of 1 year on home enteral nutrition (HEN) providing 30 kcal/kgBW/day and 1.2 g prot/kgBW/day. Out of the 47 patients, 29 (18 M, 11 F) had a peripheral onset of the disease (Group P) and 18 (8 M, 10 F) had a bulbar onset of the disease (Group B). We studied the two groups in order to asses if nutritional support is able to ameliorate weight and BMI and if differences exist in HEN efficacy depending on modality of onset. Results: The results of this preliminary analysis are shown in the table: Table Changes in weight and BMI in ALS undergoing HEN, according to disease modality of onset Peripheral onset (P) Bulbar onset (B) Total, n (M, F)

29 (18 M, 11 F)

18 (8 M, 10 F)

Age at diagnosis (y ± SD)

54 ± 14

61 ± 10 (p = 0.05 vs. P)

Conclusions: In B ALS patients the need for PEG placement tends to occur earlier than in P patients. Both P and B ALS patients significantly lose weight before PEG placement. One year of HEN may maintain weight and BMI in ALS patients, irrespective of disease modality of onset. References 1. Mitchell JD, Borasio GD (2007). Amyotrophic lateral sclerosis. Lancet. 369:2031–41 2. Hardiman O. Symptomatic treatment of respiratory and nutritional failure in amyotrophic lateral sclerosis. J Neurol. 2000;247(4):245–51 (PubMed: 10836614) 3. Desport JC, Preux PM, Truong TC, Vallat JM, Sautereau D, Couratier P. Nutritional status is a prognostic factor for survival in ALS patients. Neurology 1999;53(5):1059–63 (PubMed: 10496266) 4. Mazzini L, Corra T, Zaccala M, Mora G, Del Piano M, Galante M. Percutaneous endoscopic gastrostomy and enteral nutrition in amyotrophic lateral sclerosis. J Neurol. 1995;242(10):695–8 (PubMed: 856853)

An unusual case of leukopenia I. Kushta, M. Muscaritoli, S. Lucia, A. Molfino, G. Gioia, F. Rossi Fanelli Department of Clinical Medicine, Sapienza Universita` di Roma, Roma, Italy Case report: A 59-year-old man underwent in 1998 an extensive duodenal-jejunal resection because of intestinal ischemia resulting in short bowel syndrome (SBS). Total parenteral nutrition (TPN) was introduced after surgery to prevent malnutrition/dehydration. Minimal oral feeding was allowed and subsequently withdrawn because of vomiting and diarrhoea. Despite TPN from 2000 up to 2009 severe body weight loss ([40 kg) occurred. The patient had also experienced severe pancytopenia and several hospital readmissions due to

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infectious episodes. He was first admitted to our hospital because of pneumonia in June 2010. On admission we discovered severe anaemia (RBC 2.540.000/mcL, Hb 8.6 g/dL, Hct 25%), leukopenia (WBC 1.850/mcL, neutrophils 350/mcL) and thrombocytopenia (platelets 65.700/mcL). Serum biochemistry revealed: iron 104 mcg/dL (n.v. 80–140), TIBC 174 mcg/dl, ferritin 588 ng/mL, vit B12 533 pg/mL, folate 10.6 ng/mL, Zn 66 mcg/dL, transferrin 185 mg/dL. The peripheral blood smear showed anisopoikilocytes. Bone marrow aspiration revealed hypercellularity and \5% blasts. Karyotype was normal. Abdominal US scan revealed mild steatosis. A copper deficiency syndrome was then hypothesized. Serum copper (n.v. 70–150) and ceruloplasmin (n.v. 20–50) were markedly reduced: 21 mcg/dL and 13.8 mg/dL, respectively, despite weekly multiple trace elements administration. Cupruria was low (2.5 mcg/24 h). Oral copper supplementation (0.9 mg/day) was started followed by intravenous administration (0.15 mg/day) of a tailored galenic preparation containing copper sulphate pentahydrate. Anaemia and leucopoenia were reverted after 2 months of i.v copper (RBC 4.060.000/mcL, Hb 14.5 g/dL, WBC 4100). Ceruloplasmin (27.3 mg/ dL) and copper (85 mcg/dL) were also increased. Discussion: Although copper deficiency is a rare clinical entity it may occur as a complication of prolonged TPN in SBS. Copper plays a key role in several enzyme activities involved in body homeostasis and its deficiency can lead to anaemia, leukopenia, neutropenia, skeletal abnormalities and other clinical manifestations. The RDA recommendation in patients undergoing long term TPN with copper deficiency is 0.3–0.5 mg/day iv. Assessment of copper status should be performed when other causes of anemia and pancytopenia in long term TPN patients have been excluded.

western blotting. Immunotyping of the DGC components was performed using anti-n-NOS monoclonal antibody and anti-Syntrophin monoclonal antibody that identified all three isoforms of Syntrophin. Results: As expected, the growth of the AH-130 ascites hepatoma induced significant weight and GSN muscle loss. Syntrophin and n-NOS were both reduced in tumor bearing rats. The mean Syntrophin normalization ratio was 0.67 (SD ± 0.44) and 0.72 (SD ± 0.28) for tumor bearing rats and control group, respectively (p = 0.81). The mean n-NOS normalization ratio was 0.73 (SD ± 0.38) and 1.24 (0.28) for cancer and control group, respectively (p = 0.05). Conclusion: These preliminary data indicate that two DGC components tend to be hypoexpressed in the muscle of tumor bearing rats, suggesting that perturbations of this system might be implicated in cancer cachexia. If confirmed in larger series, and for other DGC components, these data could allow identify in the DGC a novel target to combat muscle atrophy in cancer cachexia.

Dystrophin glycoprotein complex (DGC) and cancer cachexia: a novel target to combat muscle atrophy?

Background: A good glycemic control reduces the risk of vascular complications in type 2 diabetes mellitus, whereas the influence of glycemic control on the development of diabetic cardiomyopathy is still under evaluation. The study was aimed to evaluate the relationship of glycemic control with left ventricular (LV) morpho-functional characteristics and plasma levels of matrix metalloproteinases (MMPs) in type 2 diabetic patients without overt cardiovascular disease. Methods: Diabetic patients were consecutively enrolled and divided into two groups, according to glycemic control: HbA1c B7% and HbA1c [7%. The patients underwent: 24 hour blood pressure (BP) monitoring, echocardiography and plasma measurement of MMP-9 and -2, markers of collagen metabolism. Results: Forty-eight patients were enrolled (28 men, mean age 55 ± 9 years): 17 with HbA1c B7% and 31 with HbA1c [7%. The 2 groups were not different for age, gender, duration of diabetes, BMI and systolic and diastolic BP throughout the 24 hours. LV mass index was normal in all the patients and similar between the 2 groups (80 ± 18 g/m2 vs. 86 ± 20 g/m2, ns). With regard to LV diastolic function, patients with HbA1c [7% showed lower transmitral E/A ratio (0.9 ± 0.2 vs. 1.1 ± 0.2, P \ 0.05) and Em/Am ratio (from Tissue Doppler Imaging) (0.9 ± 0.3 vs. 1.1 ± 0.3, P \ 0.05) and higher E/E0 (6.6 ± 2.1 vs. 4.7 ± 0.9, P \ 0.01). E/E0 ratio was significantly correlated with HbA1c (P \ 0.05). Plasma MMP-9 was detected in 77% of patients with HbA1c [7% and in 35% of patients with HbA1c B7% (P \ 0.05); few patients had detectable levels of plasma MMP-2 (23% of patients with HbA1c[7% and 6% of patients with HbA1c B7%, ns). Conclusions: These In type 2 diabetic patients a poor glycemic control is associated with a greater impairment of LV diastolic function and a higher prevalence of plasma MMP-9 expression. The latter finding indicates a potential role of plasma MMP-9 as marker of preclinical cardiac dysfunction in diabetic cardiomyopathy.

S. Lucia, M. Muscaritoli, M. Esposito, C. Ramaccini, P. Costelli, Z. Aversa, F. Rossi Fanelli Dipartimento di Medicina Clinica, Sapienza Universita` di Roma, Roma, Italy Background: Cancer cachexia is a devastating syndrome that complicates cancer. The prominent feature of cancer cachexia is skeletal muscle atrophy that leads to reduced physical function, reduced autonomy, impaired quality of life and increased mortality. The molecular mechanisms underlying muscle atrophy in cancer cachexia are still largely unknown. The dystrophin glycoprotein complex (DGC) is a multimeric structure composed by transmembrane, cytoplasmic and extracellular proteins that hold both structural and signal transduction properties. DGC components include dystrophin, dystroglycans, sarcoglycans, dystrobrevin, syntrophins, sarcospan, caveolin-3 and neuronal nitric oxide synthase (n-NOS). In Duchenne/Becher dystrophy, a qualitative or quantitative impairment of DGC function is responsible for skeletal muscle atrophy. It has been hypothesized that DGC dysfunction might be implicated in other forms of muscle atrophy, including cancer cachexia. Aim: Aim of the study was to assess whether perturbations of the DGC complex occur in an experimental model of cancer cachexia. Materials and Methods: Cancer cachexia was induced by an i.p. inoculum of 108 Yoshida hepatoma cells in adult male Sprague– Dawley rats (TB, n = 4). Five non-TB rats were used as a control group (C). All rats were sacrificed under light anesthesia 10 days after inoculum, and gastrocnemius (GSN) muscles dissected and immediately frozen in liquid nitrogen and stored at -80C until analysis. Subsequently, muscle proteins from gastrocnemius muscle homogenates were extracted using the Lowry method and then processed by

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Glycemic control in type 2 diabetes mellitus: relationship with left ventricular diastolic function and matrix metalloproteinases A.M. Maresca1, C. Marchesi1, C. Mongiardi1, F. Annoni1, L. Merletti1, E. Nicolini1, I. Franzetti2, A. Passi3, A. Bertolini1, A.M. Grandi1, A. Venco1 1

Department of Clinical Medicine, University of Insubria; 2Unit of Diabetology, Hospital of Varese; 3Department of Clinical Medicine, University of Insubria, Varese, Italy

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Liraglutide in therapy of type 2 diabetes mellitus: results from literature search M. Migale*, M. Manini**, A. Desideri*, F. Balestrini***, E. Santillo*** *Internal Medicine Unit ‘‘Villa Verde’’ Clinic, Fermo (FM); **Internal Medicine Unit, Orbetello Hospital (GR); ***Cardiovascular Disease Unit, INRCA Fermo (FM), Italy Introduction: Type 2 diabetes mellitus has been defined as a progressive disease, characterized by both insulin resistance and declining beta-cell function which lead to impaired glucose-induced insulin secretion. The incretin hormones, glucagon-like peptide-1 (GLP-1) and glucosedependent insulinotropic polypeptide (GIP) are now widely recognized as important contributors to the maintenance of glucose homeostasis. Incretin-based therapies comprising both dPP-4 (dipeptidyl peptidase-4) inhibitor and GLP-1 receptor agonist such as liraglutide, are now available for type 2 diabetic patients. Since GLP-1 is a protein, all GLP-1 agonists, including liraglutide, are proteins and so must be administered via injection. Aims: Purpose of our study was to evaluate the efficacy and safety of liraglutide therapy in adults with type 2 diabetes, based on randomized controlled trials, meta-analysis and review published in peerreviewed journals or as abstracts and assess if liraglutide offer an effective alternative to other antidiabetic drugs. Materials and Methods: A Medline search for all articles was performed on Pubmed without time of publication limits. We used the following two keywords: ‘‘diabetes’’ and ‘‘liraglutide’’. Article reference lists were also searched for relevant information, and supplemental material such as conference abstracts, drug prescribing information, and treatment guidelines were included as appropriate. Results: The literature search identified 275 potentially relevant articles for screening, 253 in English language. There were 38 randomized controlled trials (37 in English) and 4 meta-analysis (all in English). There were also 112 reviews published (102 in English). Discussion: Liraglutide is a modified form of human GLP-1 which has been demonstrated to have favourable effects on islet cell function, leading to improvements in glycemic control in the treatment of type 2 diabetes. Whereas the efficacy of the other GLP-1 receptor agonist exenatide, is limited by its relatively short half-life and consequent minor effects on fasting glucose levels, longer action of liraglutide have robust effects on fasting glucose levels and may potentially provide superior efficacy to exenatide and most oral agents. The efficacy of liraglutide as monotherapy or as combination therapy with one or two oral antidiabetic drugs was investigated in the LEAD program which includes six randomized, controlled, double-blind phase 3 studies in subjects with inadequately controlled type 2 diabetes mellitus. The LEAD program showed that liraglutide is effective in monotherapy, and even superior to sulfonylurea, with the additional benefits of weight loss and less hypoglycemia. Furthermore, as add-on therapy to a single oral antidiabetic drug, it is non-inferior to sulfonylurea, and superior to glitazone, again with the helpful effect on weight. Beyond the effects on glycemic control and weight, liraglutide has demonstrated pleiotropic effects that may enhance its therapeutic effect in patients with type 2 diabetes. Liraglutide was associated with benefits in regard to cardiovascular profiles. Most patients had decreasing arterial systolic pressures, had meaningful A1c level reductions, and experienced vasodilation. Among subjects who lost weight, most had improved lipid profiles. In patients on liraglutide therapy, some transient increases in heart rate were observed, but they did not appear to be clinically significant in most studies.

S357 The most evident adverse events associated with liraglutide were gastrointestinal. In the LEAD Program trials, nausea was more frequent in the liraglutide treatment groups relative to comparators. Formation of anti-liraglutide antibodies was reported to be low and not to be associated with loss of efficacy of the drug. Liraglutide was related with a low risk for hypoglycemia unless associated with a secretagogue or insulin. Conclusions: Available data suggest that the characteristics of liraglutide make it a valid alternative or addition to oral antidiabetic agents and/or insulin. Future research will be needed to determine the potential long-term benefits of liraglutide and assess its role in diabetes treatment algorithms.

Severe multi-organ complications in young adult after bariatric surgery M.L. Morieri, P. De Palma, E. Lodi, G. Zuliani, A. Passaro University of Ferrara, Section of Internal Medicine, Gerontology and Clinical Nutrition, Ferrara, Italy A 36 years old girl was referred to Ophthalmology Emergency Room (O.E.R.) for progressive loss of virus, with intensive xerophthalmia and itching, she had almost total blindness on right eye, and a 7/10 loss of visual acuity in left eye; the discharge diagnosis was bilateral keratoconjunctivitis sicca and right corneal ulceration. Suspecting Sjogren Syndrome she was addressed to Rheumatological service. The following day the young girl went to Hospital E.R. for lipotimic episode related to left renal colic, with U.S. detection of nephrolithiasis and moderate pyelic dilatation. The day after, because of worsening of virus loss she came back to O.E.R. where, in consideration of her history and first physical and labs findings, was assigned to our Department of Internal Medicine. Indeed she was excessively thin (BMI 18.5 kg/m2) and suffering, her skin was hypoelastic and flaccid with diffuse multiple clusters of chronic abscesses (most of which healed) predominantly in genital and perineal areas associated to diffuse muscular hypotrophy. Soft pain in right hypochondrium, positive left Giordano’s sign, 2/6 L mitral systolic murmur and legs edema were detectable. First lab evaluation indicated macrocytic anaemia (Hb 9.9 g/dl, MCV 104 fl), mild neutrophilic leukocytosis (WBC 13980/mm3, N 8440/mm3), increased CRP (4.10 mg/dl) and marked reduced hepatic function (proteins 5.1 g/dl; albumin 2.3 g/dl; cholinesterase 2377 U/L; total cholesterol 75 mg/dl; LDL estimated 14 mg/dl; triglycerides 29 mg/dl).The anamnesis was really important in diagnostic process. She was obese since adolescence, with early developing of related conditions, like polycystic ovary syndrome and hypertension; at 28 years she delivered a premature baby. At 31 years old she reached her maximum BMI (47.9 kg/m2) and a biliopancreatic diversion was performed. Then she reported an uneventful postoperative course and a weight loss of 60 kg (BMI 25,4 kg/m2) with subjective well-being for 4 years. Later on, associated to further weight loss, her conditions started to worsening, developing comedonal acne and hidradenitis suppurativa, developing amenorrhea and with beginning of visual disorders (reported visits to several specialists without improvement). Our diagnostic hypothesis was a severe malnutrition condition related to malabsorptive-restrictive bariatric surgery associated to ocular and cutaneous complications (with suspected infectious disease, autoimmune disorder and phagocytic dysfunction), hepatic failure and suspected alteration of hypothalamic–pituitary–adrenal axis. Considering the critical conditions we immediately started treatment with very high dose of fat-soluble vitamins supplementation (Retinyl palmitate 200.000 UI/die orally, i.m. Cholecalciferol 100.000 UI/die, a-Tocopherols 400 UI/die), off-lable use of i.v. Glutathione 600 mg/

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S358 die for its antioxidants effect and a broad-spectrum antibiotic coverage. Meanwhile laboratory evaluation indicated severe vitamin D deficiency (10.2 mg/ml), hypocalcaemia (2.07 mmo/l corrected for albumin), iron deficiency, with normal levels of vitamin B12 and folic acid and steatorrhea. The coagulation tests, autoimmune screening, hypothalamic–pituitary–adrenal axis and thyroid function appeared normal. Vitamin A was not detectable in our labs. A BioelectricalImpedance-Analysis confirmed an increased total body water (61.3%), reduced fat mass (18.7%) and body cell mass (46.2%). Knowing the possible systemic complication of malnutrition we executed Echocardiography and Electromyography. During hospitalization several ophthalmologic examinations were performed, prescribing specific treatment and an amniotic membrane transplantation on right eye was successfully performed. Three week after admission she was discharge with almost total recovery of left visual acuity, waiting for corneal transplantation on right eye, with improved in overall physical condition. One year after, we are still following the patient, giving her an holistic therapeutic approach, monitoring the efficiency of the prescribed treatment (with individualized diet) and avoiding iatrogenic hypervitaminosis. Currently her BMI is 25 kg/m2, the lab findings are perfect included fat-soluble vitamins levels, she come back to work, her quality of life increased significantly and is still waiting for corneal transplantation. Malnutrition and hypovitaminosis following bariatric surgery is well known in literature. In Our opinion this is due to the current indications for surgery, chiefly the excess weight. Instead the indications should be the achievement of better life-style and metabolic state, focusing the patient management in post-surgery follow-up, improving the interaction between Internists and Surgeons.

Ultrasonography for measurement of visceral fat in dogs for estimation of obesity: the argo project V.O. Palmieri, P. Paradies*, S. D’Amore, M. Sasanelli*, L. Franco, V. Zaza*, L. Ceci*, G. Palasciano Internal Medicine Unit ‘‘A. Murri’’, Faculty of Medicine; *Department of Animal Health and Well-being, Faculty of Veterinary Medicine, Bari, Italy Background: Obesity is a strong predictor of increased morbidity and mortality mainly when it develops within the so-called metabolic syndrome in association to insulin-resistance. Visceral adipose-tissue accumulation, through an increased fatty acid production, may be involved in the genesis of insulin resistance and therefore, measurements of visceral fat represents an important tool in assessing risk for the metabolic syndrome. Ultrasonography (US) has been regarded as a valid tool for the accurate estimation of visceral fat, but its use in this field has not been yet well defined. (1). In order to get further insights into this topic, we have conducted an experimental study on a population of dogs in which the relationship between sonographic measurements and morphological and biochemical markers of obesity has been investigated and compared to the standard method for the evaluation of degree of fat deposition in beagles (2). Animals and Methods: Fifty-four dogs (34 spayed and 5 intact females, 11 castrated and 4 intact males) presented for routinary clinical examination at the Veterinary Hospital of the University of Bari were randomly included in the study. On the nine-point scoring system developed by Laflamme (1997) the body condition score ranged from 4 to 9 and %BF gender-specific (Burkholder & Toll 2000) ranged from 12.05 to 52.2. Dogs were considered healthy on the basis of normal results of physical examination. After a fasting period of at least 12 hours on blood samples the following serum variables were measured: glucose (GLU); total cholesterol (TC);

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 High-density lipoprotein cholesterol (HDL-C); triglycerides (TG), Serum leptin (Leptin) and C-reactive protein (CRP). The low-density lipoprotein-cholesterol (LDL-C) was calculated applying Friedewald’ formula: LDL - C=TC - [HDL-C + (TG/5)]. Dogs were examined by US for the measurement of: (1) subcutaneous fat in the postlumbar region; (2) subcutaneous (S) and (3) preperitoneal (P) fat in the cranial median abdomen; (4) visceral (V) fat in the middle abdomen. Measures (2), (3) and (4) were conducted as already described by us elsewhere (3). Results: P and V showed a strong positive correlation with back fat layer, BCS and %BF, while S correlated only with back fat layer, confirming the high reliability of US measurements. The table shows the correlation between demographic and biochemical variables and measures of adiposity and body weight (Pearson Product Moment Correlation).

Back fat layer and visceral fat ultrasound measurements in relation of BCS show the same statistical significance allowing to differentiate normal BCS group from the others and both positively correlate with serum leptin increase. Neverthless visceral fat measurement has a higher significance because it also correlate with total and HDL cholesterol. Conclusion: Our results suggest that the measurement of visceral fat by US associated with other anthropometric methods can be used for both epidemiological and clinical research on adipose tissue distribution in dogs, for monitoring and testing diet protocols and new drugs for weight loss. These results encourage the use of the sme method in humans both for prevalence and longitudinal studies. References 1. Obesity Res. 2003;12:1488–94 2. J Small Anim Pract. 2001;42:56–9 3. J Nutr. 2006;136:1–5

Mediterranean diet adherence and obesity: relationship with CRP and HOMA C. Pirri, F.M. Trovato, A. Tonzuso, A. Pennisi, G.Fabio Martines, G. Trovato e Daniela Catalano Dipartimento di Medicina Interna, Sezione di Diagnostica e Terapia Medica, Universita` di Catania, Catania, Italy The Mediterranean diet, due to its association with low morbidity and mortality for several chronic diseases, has been recognized as a model of healthy eating. Epidemiological studies and clinical interventions have shown an effect of the Mediterranean diet on metabolic and inflammatory biomarkers. Therefore, it is conceivable that the protective role of diet on these might be mediated by two pathways involving concurrently inflammation and metabolic abnormalities. Purpose of the study is to assess whether increased adherence to

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Mediterranean diet in obesity is associated with different clinical profiles in relation to inflammation and metabolic aspects. Patients and Methods: We studied 208 patients (139 F and 69 M), overweight or obese, age 46.50 ± 12.70, BMI 30.27 ± 4.46, referred for nutritional counseling. Exclusion criteria: therapy-dependent diabetes, infectious diseases or cancer, rheumatic diseases, inflammatory-granulomatous and autoimmune diseases, renal insufficiency (GFR \90 ml/min), thyroid diseases. Mediterranean diet adherence was assessed through 1-week/1 year Dietary Recall Interview carried out by dietitians and taking into account the criteria of the Mediterranean Diet Score (AMDS: range 0–55). Results: There was a negative correlation between AMDS and CRP (r = -0.312, P \ 0.0001), and was also found an inverse correlation with serum lipids: Patients who have a greater adherence to a Mediterranean diet have lower levels total cholesterol (r = -0.261, P \ 0.0001), triglycerides (r = -0.158, 0.023) and LDL cholesterol (r = 0.271, p \ 0.0001), whereas no statistically significant correlation was found between HDL cholesterol and adherence to a Mediterranean diet score. The Odds ratio also shows that high levels of adherence to Mediterranean diet is associated with lower values of CRP (OR 0.132, CI 0.071–0.248), and insulin resistance (OR 0.115, CI 0039–0.338). Conclusions: Our study suggests that adherence to traditional Mediterranean diet is associated with lower concentrations of at least one marker of inflammation and lipid risk factors in subjects without significant cardiovascular disease and without diabetes. This may partly explain the beneficial effects of this dietary profile on various chronic diseases, and confirms its probable role in secondary prevention.

S359 Hepatic insulin resistance in fatty liver: relationship with markers of atherosclerosis and metabolic syndrome components G. Privitera, T. Tomaselli, S. Calanna, A. Di Pino, L. Spadaro, M.A. Rabuazzo, F. Purrello U.O.C. of di Medicina Interna Dipartimento di Biomedicina Clinica e Molecolare Universita` di Catania Ospedale Garibaldi Nesima, Italy Introduction: fat accumulation in liver results in hepatic insulin resistance and has been associated with increased cardiovascular risk. However, it is unclear if this association is mediated through traditional risk factors or if it represents and independent risk by itself. Furthermore, pure hepatic insulin resistance in mouse models, may lead to dyslipidemia and to increased risk of atherosclerosis associated with the metabolic syndrome. The aim of this study was to assess hepatic insulin resistance (H-IR) in fatty liver (FL) and its relationship with metabolic syndrome components, carotid artery intimamedia thickness (IMT) and apoB/apoA-I ratio as markers of atherosclerosis. Patients and Methods: we studied 49 consecutive non-diabetic subjects with ultrasound mild steatosis compared with 83 non-diabetic subjects with moderate-severe steatosis matched for age and BMI. In all subjects we measured: H-IR by oral glucose tolerance test as proposed by DeFronzo, components of metabolic syndrome as defined by ATP-III, IMT and apoB/apoA-I ratio. Results: H-IR was significantly higher in moderate-severe steatosis than in mild steatosis (p \ 0.001). Among components of metabolic syndrome, H-IR was related with waist circumference (r = 0.30; p \ 0.01) and fasting plasma glucose levels (r = 0.20; p \ 0.02). When H-IR was considered as a dichotomized trait (Group 1 = B50 percentiles; Group 2 C 75 percentiles) we found that: in group 2 IMT was higher respect to group 1 (Group 2: 1.36 ± 0.08; Group 1: 1.14 ± 0.06; p \ 0.003), and remained significant after adjustment for age, sex and BMI, but this increase was modified by ApoB/apoA-I ratio. ApoB/apoA-I ratio was significantly increased in group 2 (Group 2: 0.76 ± 0.3; Group 1: 0.61 ± 0.02; p \ 0.008) and this increase remained significant after adjustment for metabolic syndrome components. Conclusions: these results show that H-IR is strongly associated with progressive liver fat infiltration and markers of atherosclerosis. ApoB/ apoA-I ratio was modified by H-IR independently of metabolic syndrome components and could be a crucial link with cardiovascular risk.

Atherogenic dyslipidemia in metabolic syndrome, type 2 diabetes and familial combined hyperlipemia: Lipid and lipoproteins profiling A. Renzi, G. Barbarossa, E. D’erasmo, G. Pigna, A. Gallo, C. Favoccia, E. Grieco, A. Montali, S. Morano, M. Colotto, P. Coletta, D. Pergolini, M. Rossetti, E. Ciociola, S. Filetti, M. Arca, M. Maranghi Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy Background and Aims: Atherogenic Dyslipidemia (AD), characterized by hypertriglyceridemia, low levels of HDL cholesterol (HDL-C) and normal levels of LDL cholesterol (LDL-C), has been related to cardiovascular disease (CVD). AD is a common feature of Metabolic Syndrome (MS), Type 2 Diabetes Mellitus (T2DM) and Familial Combined Hyperlipidemia (FCHL). Environmental and genetic factors might distinctly affect lipid profile in these three disorders. The aim of our pilot study was to compare lipid levels,

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S360 cholesterol and triglycerides (TG) content in lipoprotein sub fractions in subjects with MS, T2DM and FCHL. Materials and Methods: Two hundred and four individuals were studied: 80 subjects with MS, 85 with T2DM and 39 with FCHL. All subjects were in primary prevention for CVD and not on lipid-lowering therapy. Obese FCHL patients (BMI = [30 kg/m2) were excluded in order to avoid overlapping with MS subjects. Total Cholesterol (TC), HDL-C and TG were measured by standard assays; NON-HDL-C was calculated as TC minus HDL-C; cholesterol and TG in VLDL, Intermediate density lipoproteins (IDL) and LDL particles were measured after separation by density-gradient ultracentrifugation. Data are expressed as mean (±SD). For comparison between groups the ANOVA was used. Generalized linear model was performed for multivariate analysis (adjusting for age, sex, BMI and smoke). A p value of \0.05 was considered significant. Results: Mean age in MS, T2DM and FCHL subjects was 51 (±1.58), 60.2 (±9.88) and 46.05 (±9.72) years, respectively. As expected, BMI was significantly lower in FCHL subjects as compared to MS and T2DM. AD was present in 53.7% of patients with MS, in 23.5% of T2DM patients and in 46.1% of FCHL patients. After multivariate regression analysis, T2DM patients showed significantly lower levels of TC, TG, NON-HDL-C and significantly higher HDL-C levels as compared to MS and FCHL patients (p \ 0.001 for all). Accordingly, cholesterol in VLDL and IDL and TG in VLDL, IDL and LDL subfractions were also significantly lower in T2DM than in the other 2 groups (p \ 0.001 for all). Conclusion: In the cohorts studied, T2DM patients display a less atherogenic lipid profile as compared to patients with MS and FCHL.

Eating disorders and psychiatric comorbidity in obese subjects G. Rossi**, M. Altamura*, P. Aquilano*, L. Mendolicchio*, M. Rossetti**, T. Lo Russo**, M. Tusiano**, A. Petrone***, A. Bellomo* and E. Altomare** *Department of Medical Sciences Psychiatry Unit, University of Foggia; **Department of Medicine, Internal Medicine II, Weight and Eating Disorder Unit, Azienda Ospedali Riuniti; ***Department of Neuroscience, Psychology Unit, Azienda Ospedali Riuniti, Foggia, Italy Objective: Obesity is often associated with eating disorders. Each of these conditions shows a possible link to emotional disorders such as depression or anxiety. The aim of the study was to determine the prevalence of eating disorders in obese subjects and investigate whether eating disorders were associated with emotional disorders. Method: 118 adult obese subjects (87 F; mean age 44.5 years) with a BMI[30 (mean: 37.6 kg/m2; SD 5.16), were randomly selected from obese subjects who were referred to the Weight and Eating Disorder Unit and assessed for eating disorder within the first 3 months of 2011. The patients were assessed for current and past eating disorders using the Eating Attitude Test (EAT-26). The high-score group ([20 EAT-26) was subsequently administered the Eating Disorder Inventory (EDI-2), the IPAT Anxiety Scale Questionnaire (ASQ) and the IPAT Depression Scale Questionnaire (CDQ). Results: A total of 75 (63,5%; 60 F) of obese subjects interviewed met the criteria for Bulimia Nervosa (BN) (N = 2, 1F), Anorexia Nervosa and Bulimia Nervosa (AN-BN) (N = 1F) and Eating Disorders Not Otherwise Specified (EDNOS) (N = 72, 58 F) including Sweet Eating (SE), Emotional Eating (EE), Binge Eating Disorder (BED) and other not specified eating disorders (NSED). 20 of 75 obese subject with eating disorders (26.6%; N = 9 NSED, N = 4 BED, N = 1 AN-BN, N = 1 SE, N = 2 BN, N = 1 EE) scored higher on the EAT- 26. This high score group had significantly higher

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 scores on EDI subscales: Body Dissatisfaction (BED, AN-BN, SE, BN, NSED), Ineffectiveness (BED, NSED), Interceptive Awareness (BED), Impulse Regulation (AN-BN, BED), Ascetism (NSED, BED). They scored higher on the following ASQ subscales: Tension, Suspicious, Apprehension (BED, BN, EE, SE, NSED, AN-BN); Emotional Instability (BED, EE, BN, NSED); Lack of Control (BED, EE, NSED). 18 subjects (BED, EE, SE, NSED, AN-BN) were positive in the CDQ. Conclusion: Our results show high prevalence of eating disorders in patients with obesity. The findings suggest that obese subjects with eating disorders might be considered a subgroup deserving greater psychiatric interest for the comorbidity with emotional disorders. It is important that all obese patients are psychological assessed in routine clinical care.

Apolipoprotein CIII is an independent determinant of endothelial dysfunction in obese women F. Rossi, C. Bertone, E. Michelon, F. Miglietta, M.J. Bianco, A. Castelli, V. Santiemma Dipartimento di Medicina Sperimentale, Sapienza University of Rome, Rome, Italy Background: Apolipoprotein CIII (ApoCIII) is a 8.8 kDa glycoprotein mostly secreted by the liver and, to a lesser extent, by the intestine. ApoCIII has been documented to affect endothelial cell (EC) function and monocyte adhesion to EC. Serum ApoCIII levels have been shown to be elevated in atherosclerosis, metabolic syndrome and diabetes mellitus, all conditions associated with increased cardiovascular (CV) risk, and it has been suggested that ApoCIII should be considered an independent risk factor for CV disease. Endothelial dysfunction represents the earliest abnormality in the development of vascular disease, it is linked to subsequent atherosclerosis progression, and it is present in obesity. It has been validated as well as an independent CV risk factor and prognostic factor in CV disease. Aims: To evaluate serum ApoCIII levels in obese fertile women, without any other cardiovascular risk factor (hypertriglyceridemia, hypercholesterolemia, hypertension, diabetes mellitus), compared to age-matched controls and to assess the ApoCIII relationship with endothelial dysfunction and with endothelial progenitor cells (EPC) number. Methods: 58 obese fertile were consecutively recruited from the outpatient service of the Medical Pathophysiology Department in about 1 year. Before inclusion in the study, all candidates were screened using an extensive medical history and routine clinical screening. All tests were conducted between day 1 and 7 of their menstrual cycle. Exclusion criteria: triglycerides [150 mg/dl, previous history of cardiovascular events, presence of hypertension, diabetes mellitus, any medical treatment, smoking. A control group, without statistically difference per age composition to study group, of 10 healthy subject was enrolled. Number of circulating EPC was evaluated by 2-color flow cytometric analysis performed using monoclonal antibodies against CD133 and D34 on peripheral mononucleate cells. Endothelial function was evaluated as forearm blood flow (FBF). FBF was measured in both arms simultaneously by strain gauge plethysmography. Maximum FBF (post-ischemic vasodilator response) was estimated as mean of the three measurements. FBF peak response to ischemia was expressed as FBF ratio (FBFr) computed as maximum FBF in the experimental arm divided by maximum FBF in the contralateral arm. Results: In obese patients, plasma level of ApoCIII was increased compared to control group (mean ± D, 8.7 ± 1.3 vs. 18.3 ± 1.2, p \ 0.0005), and circulating EPC number was significantly decreased

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 compared to control group (mean ± SD, 18.6 ± 4.7 vs. 45 ± 11.3, p \ 0.001). The assessment of endothelium-dependent vasodilatation (EDV) as FBFr also showed that FBFr was significantly decreased in obese woman (mean ± SD, 19.1 ± 1.3 vs. 9.92 ± 0.5, p \ 0.001). ApoCIII plasma level was very well correlated to BMI (r2 0.42, p \ 0.0005), and an inverse correlation was found to EDV (r2 0.37, p \ 0.001) and circulating EPC number (r2 0.45, P \ 0.001). ApoCIII plasma level was very well correlated to BMI (r2 0.42, p \ 0.0005), and an inverse correlation was found with circulating EPC number (r2 0.45, P \ 0.001) and EDV (r2 0.37, p \ 0.001). In order to study the association between ApoCIII and endothelial dysfunction multivariable analysis was performed in all subjects, entering in the model only dependent variable significatively associated in univariate analysis. Adjustment for age, BMI, EPC all significantly correlated to EDV, had no effect on the association between ApoCIII and EDV. Conclusions: Our data document that ApoCIII, even in the presence of normotrigliceridemia, is strictly related to BMI. ApoCIII close direct relationship with endothelial dysfunction and inverse relationship with EPC number suggest underlying mechanisms that need to be investigated. As demonstrated in multivariate analysis the association between ApoCIII and EDV persisted after adjustment for age, BMI and EPC which, in our patients, were all significantly correlated to EDV, supporting the contention that ApoCIII may be an independent cardiovascular risk factor.

HCV genotype 1 impairs glucose metabolism promoting a more rapid progression of liver disease and metabolic syndrome A. Sellitto, L. Restivo, A. Santagata, M.C. Fascione, A. Amelia, E. Solaro, B. Guerrera, L.E. Adinolfi Internal Medicine, Second University of Naples, Clinical Hospital of Marcianise, Italy Background: Three- to tenfold increased prevalence of serum HCV antibodies have been reported in patient with type 2 diabetes (T2D) parallels an increase prevalence of diabetes in HCV infected patients. These latter showed at least a twofold excess risk of T2D. In addition, evidences suggest that glucose metabolic abnormalities are associated with a more rapid progression of liver fibrosis in CHC patients These data seem to indicate a possible viral role in the development of T2D and that such metabolic alterations might affect both progression of chronic hepatitis C (CHC) patients and response to antiviral therapy. Aim: Accordingly, we investigated the prevalence of glucose abnormalities in CHC and its relationship with viral and host factors, liver disease progression and metabolic syndrome (MS). Methods: Prospectively were enrolled 424 consecutive patients with histological diagnosis of CHC. Patients were evaluated for HCV genotype, HCVRNA, HOMA-IR, and MS (ATP III criteria). Impaired fasting glucose (IFG) and DM were defined on the bases of two plasma glucose values of [110 to\126 and C126 mg/dl, respectively, or with OGTT. Results: Patients median age was 53 years; male 53%; cirrhosis was present in 18% of cases; genotype 1 in 62% of patients; median of HCV-RNA was 570,000 UI/ml; T2D was present in 8% of patients; the overall prevalence of glucose metabolism abnormalities (IFG plus DM) was 14%; MS was observed in 9% of CHC patients. There was no association between T2D and cirrhosis. The overall glucose metabolic abnormalities were associated with viral factors: HCV genotype 1 (25 vs. 4%, in genotype non-1; p \ 0.01) and higher HCV-RNA levels (1,700,000 vs. 490,000 UI/ml, in patients without abnormalities; p \ 0.006); whereas, host factor associated with impaired glucose metabolism were: older age (p \ 0.001), higher serum levels of triglycerides (p \ 0.009), higher BMI (p \ 0.04), MS (p \ 0.0001) and IR (p \ 0.0001). Patients with IFG plus T2D showed higher prevalence

S361 and levels of hepatic steatosis (grade 2 vs. 1, in patients without abnormalities; p \ 0.01), liver necroinflammatory activity (Ishak median score: 7 vs. 5; p \ 0.003) and fibrosis (Iskak median score: 5 vs. 2; p \ 0.001). Multivariate analysis showed that independent factors associated with development of IFG/T2D were: older age (p \ 0.001) and higher serum HCV-RNA levels (p \ 0.024). Conclusions: the data show that in genotype 1 infection the levels of HCV replication directly influence glucose metabolism. An impaired glucose metabolism in CHC promotes a more aggressive course and great severity of liver disease and might modulate extra-hepatic clinical conditions associated to MS. Supported by a grant of Regione Campania.

Economic analysis and cardiovascular risk in the ROMEO clinical trial: Rethink Organization to iMprove Education and Outcomes J. Sicuro, P.V. Bondonio*, F. Cavallo§, L. Charrier§, P. Berchialla§, M. Raballo, M. Trevisan, F. Schellino, G. Grassi, P. Passera, M. Porta, M. Trento Laboratory of Clinical Pedagogy, Department of Internal Medicine; *Department of Economics; §Department of Public Health and Microbiology, University of Turin, Italy Introduction: ROMEO (Rethink Organization to iMprove Education and Outcomes) was a multicentre randomized controlled clinical trial, with a duration of 4 years, aimed at verifying the effects of group and individual care on metabolic control, quality of life and health behaviours in patients with Type 2 Diabetes Mellitus (T2DM). ROMEO showed that Group Care (GC) improves all these outcomes. Aim: To verify if GC is a cost-effective alternative to the individual traditional approach. Patients and Methods: data were obtained from 581 patients (315 followed by GC and 266 individually treated controls) from 11 diabetes clinics which completed the trial. The following direct costs (normalized in Euro 2007) were calculated: training of personnel, drugs, staff, diagnostic procedures, use of healthcare facilities, transportation costs of patients and their care givers. Finally, with the aim of verifying the impact of possible future costs of complications in the following 10 years, cardiovascular risk was calculated, at baseline and follow up, in GC patients and in controls, applying the Framingham, UKPDS and CUORE formulas. Results: at follow up patients in GC improved, compared to controls, BMI (-1.09; CI95%: -1.56/-0.62), HbA1c (-1.49; -1.63/-1.34) and quality of life (-16.8; -18.29/-15.25), all p \ 0.00.1. The total cost per patient/year was € 496.67 (468.79/524.54) for GC, and € 519.35 (488.61/550.09) for controls, p = NS. The main savings of GC were in staff work. At baseline cardiovascular risk was similar in patients on GC and controls. However, at the end of the trial, the predicted risk of events was significantly lower in the former. Conclusions: By promoting appropriate lifestyles and improving adherence to medication, GC is a cost-effective alternative to the individual traditional approach in the clinical and educational management of T2DM and, possibly, other chronic diseases.

Quality of life and vision in people with diabetes. A multicentre observational study M. Trento1, P. Passera1, M. Montanaro2, F. Bandello3, L. Scoccianti4, L. Charrier5, F. Cavallo5, M. Porta1–2

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Laboratory of Clinical Pedagogy, Department Internal Medicine, University of Turin; 2Diabetic Retinopathy Centre, Department Internal Medicine; 3Department of Ophthalmology, Hospital San Raffaele, Milano; 4Diabetic Retinopathy Centre and Laser Treatment, Institute of Ophthalmology, Parma; 5Department of Public Health and Microbiology, University of Turin, Italy

Introduction: Retinopathy is a complication of diabetes that requires regular control visits and, sometimes, treatment by laser photocoagulation. Objective: To evaluate changes in vision-related quality-of-life in patients with diabetic retinopathy using the 25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) in 3 centres for DR screening. Patients and Methods: The VFQ-25 was self-administered between 2006 and 2010 to 196 patients with visual acuity \5/10 in the better eye: 64 in Turin, 61 in Parma, and 71 in Udine. The VFQ-25 items explored 12 scales: General Health (GH) and Vision (GV), Ocular Pain (OP), Near Activities (NA), Distance Activities (DA), Vis Specific Social Functioning (VSSF), Vis Spec Mental Health (VSMH), Vis Spec Role Difficulties (VSRD), Vis Spec Dependency (VSD), Driving (D), Color Vision (CV), Peripheral Vision (PV). Socio-anagraphic variables and presence of DR, cataract and laser treatment (LT) were collected. Results: Patients the 3 centres did not differ by age, gender, occupation and diabetes duration. Multivariate analysis demonstrated that visual acuity was associated with variables GV, NA, DA, VSSF, VSMH, VSRD,VSD, D, CV e PV (p \ 0.01) and score improved significantly at increasing of visual acuity. Treatment by laser photocoagulation (-8.0; p = 0.002) and center affiliation (Parma vs. Turin: 7.9; p = 0.036) were associated with significantly lower scores of General Health; in particular in General Vision (-7.3; p = 0.001), Vis Spec Role Difficulties (-9.4; p = 0.01) and Driving (-13.4; p = 0.004). Center affiliation was associated with variation in scores for Ocular pain, Distance Activities, Vis Specific Social Functioning, Vis Spec Role Difficulties and Peripheral Vision with lower scores in Udine vs Turin. Gender was associated with highest scores in women versus men for the scales General Vision (p = 0.017), Near Activities (p = 0.006), Distance Activities (p = 0.004), Vis Specific Social Functioning (p = 0.02), Vis Spec Mental Health (p = 0.023) and Color Vision (p = 0.007). Conclusion: Ocular complications and loss of vision modify the way people perceive their own ability to function autonomously. More data should be collected to confirm this interpretation and to guide the development of more appropriate settings to improve approach and support to patients.

Gender differences in an occupational obesity outpatient clinic L. Vigna*, C. Novembrino**, R. De Giuseppe***, F. De Liso***, L. Airaghi****, P. Bonara****, L. Riboldi*, F. Bamonti** *Medicina del Lavoro1; **Dipartimento di Scienze Mediche e; ***Fondazione Confalonieri Universita` degli Studi di Milano; ****Medicina Interna 1b; Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milano, Italy Introduction: Gender Medicine focuses on the impact of gender on human physiology, pathophysiology, and clinical features of diseases. The attention to the impact of gender differences on the pathophysiology and, therefore, on the management of the most common social diseases—such as obesity, cardiovascular diseases, and diabetes, to list a few—is both needed and lacking. Obesity is associated with several changes in serum lipid metabolism, including increase in total cholesterol, LDL cholesterol, and

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 triglyceride concentrations and a reduction in HDL cholesterol serum concentration of about 5%. The last effect may be most important since a low serum HDL cholesterol concentration carries a greater relative risk of coronary heart disease (CHD) than hypertriglyceridemia. The aim of our study is to analyze the gender differences in an obese population, focusing on lipid metabolism changes, so deleterious for the cardiovascular risk profile. Patients and Methods: A complete clinical assessment was performed in 172 occupational obese subjects (40 males and 132 females; mean age ± SD: 48.6 ± 12.3 and 53.2 ± 12.5 years, respectively). Serum oxidized LDL levels were measured during the endocrinemetabolic evaluation, together with lipid panel and plasma homocysteine (tHcy) levels, an independent risk factor for cardiovascular diseases. SigmaStat 3.5 program for Windows was used for statistical analysis. For the comparison of mean values between males and females, Mann–Whitney test was used, and the comparison of the values among the groups categorized by the clinical data was analyze by ANOVA test. Correlations between oxidized LDL, tHcy, and other clinical parameters were performed with Spearman rank order correlation analysis. P values less than 0.05 were considered statistically significant. Results: Obese males showed some significant differences in lipid metabolism compared with females: total cholesterol levels were lower and triglycerides were higher (203.5 ± 42.6 vs. 222.2 ± 45.9 mg/dL, p = 0.006; 133.1 ± 77.6 vs. 107.8 ± 65.6 mg/dL, p = 0.019; respectively). No significant differences were observed when HDL cholesterol and oxidized LDL levels were compared, despite a relevant percentage of abnormal values in both groups. Plasma tHcy was significantly higher in males than in females (12.1 ± 3.1 vs. 10.5 ± 4.4 microM; p \ 0.0001) and tHcy levels were higher than cut-off (10 microM) in a very large group of males (82.5% in males vs. 36.8% in females; p \ 0.0001). Serum oxidized LDL correlated significantly with both total cholesterol and LDL cholesterol (r = 0.59, p \ 0.0001; r = 0.6, p \ 0.0001) whereas an inverse relationship, although not significant, was observed with HDL cholesterol (r = -0.13, p = 0.09). Anthropometric data, such as waist circumference and BMI, showed no correlations with plasma oxidized LDL. Moreover, no relationship was found between plasma oxidized LDL and a positive family history for cardiovascular diseases. Conclusions: These preliminary data suggest that gender differences in lipid metabolism are peculiar in obese individuals. It’s well known that the lipoprotein risk factors for cardiovascular diseases are somewhat different in women compared to men. Low HDL cholesterol, rather than high LDL cholesterol, is more predictive of coronary risk in women and the total cholesterol concentration appears to be associated with cardiovascular diseases only in premenopausal women or at very high levels. Triglycerides appear to uniquely influence coronary risk in older women, especially at levels above 400 mg/dL. In our study population some gender differences were maintained, while others were changed, i.e. HDL cholesterol levels, similar in both groups, lacking the favourable gap observed in non obese women. Moreover, many obese subjects showed pathological changes in HDL cholesterol and oxidized LDL, regardless of gender, and these lipid profiles undoubtedly increases the risk for cardiovascular diseases, especially in association with markers of inflammation and thrombosis, such as homocysteinemia. In conclusion, pathophysiological derangement in obesity have a role in unfavourable changes observed in lipid profile of obese women, increasing the risk for cardiovascular disease, which would become similar to that of their male peers.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Prediabetes increases cardiovascular risk in occupational obese subjects L. Vigna*, D. Bignamini**, C. Novembrino***, L. Airaghi**, R. De Giuseppe****, F. De Liso****, F. Bonara**, L. Riboldi*, F. Bamonti*** *Medicina del Lavoro1; **Medicina Interna 1b; ***Dipartimento di Scienze Mediche e; ****Fondazione Confalonieri Universita` degli Studi di Milano; Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milano, Italy Introduction: Obesity is associated with a number of risk factors for atherosclerosis, including hypertension, insulin resistance, and glucose intolerance. However, in the Framingham Offspring Study, obesity as measured by BMI significantly predicted the occurrence of cardiovascular diseases in adults, after adjusting for traditional risk factors. Common carotid artery intima-media thickness (IMT) is a surrogate marker of atherosclerosis, linked to the atherosclerotic process because of its association with known cardiovascular risk factors. Intima-media thickness is a noninvasive marker of early, preclinical atherosclerosis in high-risk children. In adult population studies, there was a moderate, graded positive relationship between carotid IMT and the presence of coronary atherosclerosis. Because preclinical atherosclerosis is common in prediabetes, we studied the prevalence of this condition among obese prediabetic subjects by B-mode ultrasound imaging and Doppler ultrasound and searched a correlation between ultrasound results and atherosclerosis biomarkers. Patients and Methods: A complete clinical assessment was performed in 172 occupational obese subjects (40 males and 132 females; mean age ± SD: 48.6 ± 12.3 and 53.2 ± 12.5 years, respectively). Plasma oxidized LDL and homocysteine (tHcy) levels were measured during the endocrine-metabolic evaluation, associated with lipid profile and HbA1c. Every subject underwent a carotid B-mode ultrasound imaging and Doppler ultrasound to measure IMT bilaterally at the level of the common carotid artery and its bifurcation and to detect the presence of any plaques. Obese subjects were divided in three groups: non diabetic subjects (HbA1c \5.7%), prediabetic subjects (5.7% C HbA1c B 6.4%), and diabetic subjects (HbA1c [ 6.4%). SigmaStat 3.5 program for Windows was used for statistical analysis. For the comparison of mean values between the three patient groups, Mann–Whitney test was used, and the comparison of the values among the groups categorized by the ultrasound data was analyze by ANOVA test. P values less than 0.05 were considered statistically significant. Results: Based on the values of HbA1c, 40.2% of obese subjects were non diabetic, 47.3% were in prediabetes status, and 12.5% were diabetic. There is no significant differences in the prevalence of these three conditions between males and females. It’s noteworthy that there are significant relationships between HbA1c values and increased carotid IMT; in the prediabetic condition there is a significant higher IMT bilaterally than in non diabetic condition (p = 0.04 on the right; p = 0.004 on the left). Moreover, the presence of any carotid plaques was frequent (27%) in the study group, and these subjects showed HbA1C significantly higher than those without plaques [6.0 (5.7–6.4) vs. 5.7 (5.4–5.9) %; p = 0.0003]. There were no differences in plasma oxidized LDL and tHcy levels between obese subjects with or without carotid plaques. Conclusions: In our study we found a high prevalence of impaired glucose metabolism, especially prediabetes, in obese subjects. The obese subjects with prediabetes had ultrasound signs of subclinical atherosclerosis, i.e. increased carotid IMT and/or plaques,

S363 even without abnormal detectable plasma levels of oxidized LDL and tHcy. Obesity is reaching epidemic proportions in the world; its association with cardiovascular diseases can lead to an increase in mortality and morbidity, mainly when impaired glucose metabolism is associated. A range of noninvasive screening tools such as ultrasound imaging of carotid artery intima-media thickness may help reducing the morbidity and mortality of patients with obesity because of early detection of subclinical cardiovascular disease and active monitoring of the effectiveness of therapy.

Miscellanea Severe hypercholesterolemia in congenital analbuminemia: still an unanswered therapeutic dilemma F. Albanese, M. Del Ben, T. Augelletti, S. Bartimoccia, R. Carnevale, E. Catasca, L. Perri, P. Pignatelli, F. Angelico Dipartimento di Medicina Interna e Specialita` Mediche, -‘‘Sapienza’’ Universita` di Roma, Italy Analbuminemia is a rare autosomic recessive inherited disorder in which subjects have little or no plasma albumin. Patients with congenital analbuminemia are essentially asymptomatic. The body is able to compensate for the lack of albumin with the synthesis of immunoglobulins and other serum proteins and notably with an increased secretion of apolipoprotein-B from the liver. Therefore, a severe, compensatory hypercholesterolemia characterized by enhanced LDL-cholesterol levels is the prominent serum alteration in most patients with congenital analbuminemia. However, so far, very few patients with congenital analbuminemia have been reported with a long term follow-up during adult age. Therefore, whether patients are at high cardiovascular risk is a major concern, although some investigators believe that the condition does not lead to premature atherosclerosis. Moreover, there is no consensus on the indication for treatment of compensatory hypercholesterolemia. Congenital analbuminemia was diagnosed in a 35 years old male and in a 43 years old unrelated woman. The first patient which is the only one in whom a case of compound heterozygosity for novel mutations in the albumin gene was detected, was essentially asymptomatic except for some lipothymic events and the presence of mild ankle oedema treated with pressure stockings. The female patient suffered of severe carotid atherosclerosis and peripheral arterial disease and underwent endarterectomy at age 65. Both patients had less that 1.0 g of serum albumin, slightly increased serum alpha1-antitripsin, ceruloplasmin, transferrin, C3, IgG and IgM immunoglobulins and severe hypercholesterolemia (387 mg/dl and 496 respectively). However, no corneal arcus and other clinical signs of dyslipidemia were present. After a single 20 g human albumin infusion both patients showed a remarkable decrease of total and LDL cholesterol, sCD40L, and markers of oxidative stress (urinary 8-isoprostanes and serum NOX2). Treatment with atorvastatin was started in the male patient at the daily dose of 10 mg, which was increased to 20 mg at week 5 and to 40 mg at week 21. Total and LDL-C dropped by 37.7% and by 50.6%, respectively, and HDL-C increased by 13.4% in response to atorvastatin 40 mg. A major decrease of total and LDL-C and of apolipoprotein-B (-34.2, -40.8 and -25.6%, respectively) was already present after the first 4 weeks on treatment at atorvastatin 10 mg. At the end of the drug period, apolipoprotein-B and lipoprotein (a) were decreased by 18.7 and 19.7%, respectively, and apolipoprotein-A1 was increased by 65.0%. The patient remained asymptomatic without any evidence of oedema, difficulties in maintaining normal blood pressure and other clinical consequences. This

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S364 study is the first to demonstrate the efficacy, tolerability and shortterm safety of atorvastatin for the treatment of severe compensatory hypercholesterolemia in a patient with congenital analbuminemia. However, after 1 year on low-cholesterol treatment, oedema of the ankles and lower legs intensified. Statin therapy was stopped and the patient received replacement therapy with six 20 g human albumin infusions over a period of 4 weeks. At the end of the first infusion, brachial artery flow-mediated dilation (FMD), a surrogate marker of endothelial dysfunction, increased from 0 to 7% and maintained the same value during the following 30 days, when serum albumin increased from 0.8 to 1.9 g/dl and a progressive decrease in total and LDL cholesterol was observed (TC from 391 mg/dl to 273 mg/dl; LDL-C from 312 mg/dl to 196 mg/dl). A major improvement of lower legs oedema was also observed. This is the first study to demonstrate the improvement of endothelial dysfunction, serum lipids and markers of oxidative stress after infusion of albumin in a patient with congenital analbuminemia. The utility of treatment of hypercholesterolemia remains still under debate.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Specific therapy with Anarinka was started, but the patient was readmitted in the Intensive Unit and died after 15 days for irreversible respiratory failure. Erdheim–Chester disease is a rare and severe disease: from 1930, when the first two cases were described, a total of 250 cases have been documented. There is no standard treatment for Erdheim– Chester disease owing to its rarity, while several options including steroids, various cytotoxic agents and hematopoietic stem cell transplantation have been reported with variable effects. IFN-alfa has recently shown to be a promising treatment and, if the patients have poor tolerance or if there are contraindications, recombinant IL1Ra (anakinra) can be alternatively used. The prognosis is poor, approximately 3 years after the diagnosis, with global survival depending on the stage of disease at the moment of diagnosis. The most common causes of death are heart and pulmonary involvement.

A rare and severe disease in internal medicine

Obstructive sleep apnea syndrome, endothelial dysfunction and oxidative stress

A. Artom, R. Goretti, S. Rattenni, M. Uccelli, P. Artom, A. Provaggi, A. Bovero

T. Augelletti, F. Angelico, F. Albanese, M. Brunori, R. Carnevale, M. Fabiani, L. Loffredo, C. Nocella, L. Polimeni, M. Del Ben

Ospedale Santa Corona, Pietra Ligure (SV), Italy

I Clinica Medica, Dipartimento di Medicina Interna e Specialita` Mediche, Universita` Sapienza, Roma, Italy

A 53 years old man was admitted in the Neurosurgery Department after a brain MRI for recent onset of headache and diplopia. The MRI showed two probable meningiomas, the biggest at the foramen magnum and the second one with left endo-orbital intraconal development. The patient reported, in addition to neurological symptoms, recent onset of leg pain. Nothing more at the past history. After a preoperative angiography and normal routine examinations (except relevant signs of fibrosis at the Chest X-Ray, dilatation of the right chambers at the echocardiography and blood gas values of pO2 below normal with pcO2 higher than normal), the biggest lesion was removed by means of a suboccipital left retrocondylar craniectomy to confirm the clinical and radiological hypothesis of meningioma. Histology was instead compatible with non-Langherans Histiocytosis (Erdheim-Chester Disease). The patient was transferred to the Medicine Department, where a CT scan of the chest was performed (severe diffuse fibrosis), together with CT-PET (intense and heterogeneous pathological accumulations involving in toto both lungs; more abnormal accumulations in the maxillary sinuses on both sides), X-ray of the skeleton (signs of osteosclerosis in the maxillary, temporal and frontal bones, osteosclerosis with cortical thickening of tibiae and distal femur). During the hospitalization polyuria and polidipsia appeared: secondary acquired diabetes insipidus was diagnosed and a rapid improvement was observed with desmopressin nasal inhalations. At the same time therapy with prednisone and interferon was started, with slight clinical improvement. The patient was discharged with periodical Day-Hospital follow up. After a month of relative clinical stability he was readmitted in the Medical Department for dyspnea, with phlogosis signs, severe mixed respiratory failure, leg edema compatible with initial heart failure, confirmed by elevated Pro-BNP values. After 48 hours the patient was transferred to the Intensive Unit for quick deterioration of the respiratory function. The clinical and radiological pattern was suggestive of intercurrent pneumonia in severe pulmonary fibrosis and initial heart failure: after initial necessity of mechanical ventilation, empirical antibiotic and cardiac therapy, the patient was extubated and tracheostomized, to maintain acceptable values of blood gas without respiratory support.

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Background: Obstructive sleep apnea syndrome (OSAS) is known to be an important cardiovascular risk factor and is becoming an emerging public health problem. Recently several studies have provided evidence supporting an increase of oxidative stress in patients with OSAS. Both oxidative stress and inflammation are major components in the initiation and development of endothelial dysfunction, which is widely accepted as an early marker of atherosclerosis. Thus, chronic low-grade inflammation, oxidative stress, metabolic abnormalities and endothelial dysfunction in OSAS could accelerate atherogenesis. Aims of our study were to assess the association between OSAS, endothelial dysfunction and oxidative stress and to evaluate the effect of nasal continuous positive airway pressure (CPAP) on endothelial dysfunction and on the levels of systemic oxidative stress in patients with severe obstructive sleep apnea. Methods: We studied 138 consecutive patients because of suspected metabolic disorders with heavy snoring and possible OSAS syndrome. Patients underwent a clinical and biochemical work up and performed unattended polysomnography. Patients with severe OSAS were prescribed CPAP treatment. Arterial dysfunction was assessed by the measurement of flow-mediated dilation (FMD). Results: Out of the 138 patients who performed overnight polysomnography, 47 had a primary snoring and 91 had a positive polysomnography for OSA. Out of these, 61 had mild/moderate and 30 severe OSA. A strong positive association was observed between OSA severity and the indices of central obesity, i.e. body mass index (p = \0.01) and waist and hip circumferences (p \ 0.001). In addition, a positive association was observed with serum insulin and HOMA-IR level and with urinary 8-isoprostanes concentration. Furthermore, a statistically negative association was observed between FMD and OSA severity. A statistically significant increase in the prevalence of central obesity was observed from snorers to subjects with severe OSAS (p = 0.012), although a positive trend was also seen for the other components of the metabolic syndrome (MS). Apnea-hypopnea index (AHI) was significantly correlated with the indices of central obesity and with urinary 8-isoprostanes (r = 0.298, p \ 0.001). In turn, urinary 8-isoprostanes were positively correlated with gp91phox (r = 0.250, p \ 0.01) and negatively correlated with

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 NOx (r = 0.360, p \ 0.001). A negative correlation was also observed between FMD and waist circumference (r = -0.199; p \ 0.05), serum insulin and triglyceride levels (r = -0.241; p = 0.01 and r = -0.238; p \ 0.01, respectively) and the number of components of metabolic syndrome (r = -0.335; p \ 0.001). In a stepwise multiple regression analysis, metabolic syndrome (t = 4.63, p \ 0.001) and urinary 8-isoprostanes (t = -2.02, p \ 0.05) were the only independent predictors of FMD. In 10 out of the patients with severe OSAS, who were compliant to CPAP treatment over a period of 6 months, a statistically significant decrease of urinary 8-isoprostanes and of gp91phox (p \ 0.05 and p \ 0.01, respectively) was observed. Conclusions: OSAS severity is strictly associated to insulin resistance, oxidative stress and endothelial dysfunction, known to be responsible of the initiation and the progression of the atherosclerotic disease. Compliance to CPAP improves oxidative stress and ameliorates the indices of OSAS severity.

Cognitive errors and missed diagnoses: a new perspective for an old problem M. Barchetti, M. Franchini, S. Rosi, M. Fiorini, A. Parise, E. Gottardi Unita` Operativa di Medicina d’Urgenza e Pronto Soccorso, Ospedale di Sassuolo, Italy Diagnostic reasoning is a critical aspect of clinical performance, it is vulnerable to a variety of failings the most prevalent arising through cognitive influences. The impact of diagnostic failure on patient safety does not appear to have been fully recognized. Ideally all information used in diagnostic reasoning is objective and all thinking is logical and valid, but these conditions are not always met. Benchmark studies on medical error found diagnostic failure more common in the three disciplines in which diagnostic uncertainty appears to be the highest: internal, family and emergency medicine. The cognitive psychology is the science which studies the way or method of reasoning, the way or method of judging, the decision making process. None of the processes listed above can be flawless so that errors can be expected and hopefully eschewed. Errors are common, all individuals make mistakes and tend to do it in a sort of peculiar and systematic way. Since several years now even the nature of clinical reasoning has been put under investigation in the hope of finding out strategies aimed at improving doctor’s performance. Diagnostic mistakes are common too, most of the time totally ignored; that’s why possible solution to the problem is looked for. Many diagnostic medical errors are not technical or cultural (15%) but cognitive (80%) that is related to faulty reasoning. The clinical reasoning often takes the doctor to a quick and conclusive judgment, but at the same time contains potential sources of error. These cognitive errors have been singled out as follows: ‘‘availability error’’, ‘‘anchoring error’’, ‘‘framing error’’, ‘‘hasty conclusion’’, ‘‘representation error’’, ‘‘attribution error’’, affectivity error’’ and so on and so forth. Exercises have been worked out, apt at recognizing errors and which type of error are we more frequently exposed to, as well as correcting actions possibly implemented. On the ground of these considerations, we are trying to put in practice in our E.R. and Emergency. Medicine Unit a program to improve our clinical audits, to discover cognitive errors by means of two tools: the diagnostic error feed-back and the cognitive meta-analysis (metacognition). The first step is to recognize in a systematic way that a mistake has been made, the

S365 second step is to analyze the reasoning that brought us to that error. We present our experience in studying cognitive pitfalls in reasoning, trying in a different way to learn from mistakes. Becoming aware of commons cognitive errors might lead to sustained improvement in patient care.

An unusual presentation of idiopathic myelofibrosis: the key role of internal medicine E. Bontempelli*, G. Bulgari*, S. Spandrio *Universita` degli Studi di Brescia, Clinica Medica, Brescia, Italy; II Medicina Spedali Civili di Brescia, Brescia, Italy A previously healthy 58-years old man was admitted to a medical ward on March 2010 because of persistent fever up to 38C, mild weight loss, myalgias, migrant and asymmetrical arthralgias associated with swelling involving meanly knees, ankles, shoulders, wrists and hips. These symptoms had begun 1 month after an accidental trauma associated with a lacerated contused wound of his left leg, complicated by a dermo-hypodermitis and successfully treated with Amoxicillin Clavulanate for 10 days. On admission, the patient was conscious and co-operative, had persistent fever, blood pressure was 135/80 mmHg, heart rate was 70 beats/min., and arterial oxygen saturation was 96%. Physical examination revealed mitral systolic murmure, splenomegaly, inguinal and axillary lymphadenopathy. He had swelling and warm joints, particularly his right knee and wrist. We performed an electrocardiography and a chest X-ray, that were normal. Biochemistry showed thrombocytosis 714000/mmc, mild anemia 11.7 g/dl, elevation of C-reactive protein (CRP), alkaline phosphatase, gamma glutamyl transferase, lactate dehydrogenase (LDH) and transaminases. Blood and urine culture were persistently negative. All the infective and immunologic tests resulted negative. Skeletal X ray and testing for HLA B27, as well as peripheral blood smear, JAK2 mutation and angiotensin-I converting enzyme test were negative. In order to find out any possible cause of his persistent fever we performed transesophageal echocardiography. The scan showed dilatation and global hypokinesis of left ventricle (ejection fraction 37%) with functional mitral insufficiency and left atrial enlargement, but no evidence of endocardial vegetations. The coronary angiography was able to exclude an ischemic cardiopathy and the magnetic resonance imaging of the heart excluded the presence of myocarditis. Tumor markers, abdominal echography, total body computed tomography and later positron emission tomography were negative, except for the confirmation of splenomegaly. In the next few weeks, he developed a progressive normocytic anemia (up to 9.5 g/dl) and an increasing thrombocytosis (1000000/ mmc), persisting fever and elevated CRP, ferritin and LDH in presence of normal procalcitonin value. Liver cytolytic and cholestatic parameters gradually increased up to four-five times normal value. The clinical manifestation and evidence in laboratory and instrumental examinations led to a possible haematological origin of the disease, which was not supported by the haematologist, having the patient so many collateral symptoms; only after 2 weeks we managed to convince the colleague to perform a osteo-medullary biopsy, which finally revealed a pattern of idiopathic myelofibrosis. An hepatic agobiopsy was also solicited by the hematologist after the increasing of liver cytolytic and cholestatic parameters; it only revealed a mild aspecific hepatitis, no other pathology was found. Prednisone at low dose (10 mg once a day) was then started with a rapid resolution of the fever, joint pain and an arising of red blood cells.

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S366 The patient has been hospitalized for almost 1 month, being submitted to many expensive and invasive instrumental examinations. The hematological hypothesis was made within the first week, but strongly opposed by the hematologist for the important systemic manifestations which are uncommon in this disease. The osteomedullary biopsy was performed only 3 weeks later, after the negative evidence of all the other exams and under our pressing demand. It is sometimes difficult to carry on a correct diagnostic course when we need collaboration from other medical specialists and when the clinical presentation is not so coherent, but this is the real challenge of our job: internal medicine. It means to achieve an overall vision of the patient with the best chance to make a correct diagnosis. We should only be more self confident to carry on our ideas.

Training pharmacists and pharmacy assistants in the stage-ofchange model of smoking cessation: a randomised controlled trial in Sicily P. Caponnetto, R. Polosa, G. Piccillo Centro per la Prevenzione e Cura del Tabagismo (CPCT), Azienda Ospedaliero-Universitaria ‘‘Policlinico-Vittorio Emanuele’’, Universita` di Catania, Catania, Italy, Institute of Internal Medicine Objective: This randomised controlled study set in pharmacies in Sicily has evaluate the effect of training pharmacists in the stage-of-change model of smoking cessation and motivational interviewing. Methods: A training package based on the stage-of-change model of smoking cessation and motivational interviewing was been carried out, in February 2009, by the Centro per la Prevenzione e Cura del Tabagismo at the University of Catania. The training was been piloted on a cross-section of pharmacy personnel. The training was been used case studies of pharmacy customers, and was been focused on communication skills for negotiating change and providing on-going support and encouragement; importance of pharmacotherapy in smoking cessation was been also explained. A total of 46 community pharmacies registered in the Farmacia OK database have participated in the trial and attended a three hour training on ‘‘2008 clinical practice guideline Treating Tobacco Use and Dependence’’. Successively, pharmacies were randomly allocated by sequential allocation to the intervention or control group. The intervention group attended a 6-hour training by scheduling a initiation workshops. During the 3-month customer recruitment period, all smokers who sought advice on stopping smoking or those who bought an OTC anti-smoking product in preparation for a new attempt to stop smoking was been eligible for inclusion. Results: A total one 587 smokers participated in the study (303 intervention group, 284 control group). At 12-week, 194/303 subjects (64.4%) were lost at follow-up in active group and 198/284 (69.7%) in reference group. At 24-week, subjects who were lost at follow-up accounted for 247/303 subjects (72.5%) in active group and 256/284 (90%) in reference group. In our study, at 12-week, the quit rate were 25.7%, for intervention group and 14.4% for control group. At 24-week, the quit rate were 11.2%, for intervention group and 6.3% for control group. Conclusion: The study demonstrated the utility of the stage-ofchange model and motivational interviewing in a pharmacy setting. There was almost unanimous agreement by the workshop participants that the model was a good way of understanding stopping smoking, and that the training had made a difference to the way they counselled customers and had helped them to help their customers. This was confirmed by the customers, data demonstrated higher smoking cessation rates compared with the controls.

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 True femoral aneurysm in previous multiple iliac femoropopliteal revascularization surgery: case report and literature review M. Cavallo, A. Marigo, A. Marino, L. Novello, S. Simeoni, A. Tedesco, M. Tomsic, S. Vieno, A. Toffon* U.O. Medicina Generale O.C. Lonigo (VI); *U.O.S. Chirurgia Vascolare ULSS 5, Italy Introduction: We described the case of an 75 year old man who has referred to us for the presence of left inguinal pulsatile mass. His physiological history was positive for smoke, negative for alcohol. Remote history positive for previous multiple iliac femoropopliteal revascularization surgery (PTFE, polytetrafluoroethylene, iliac femoral bypass, biological femoropopliteotibial bypass and more embolectomy using a Fogarty catheter), hypertension, angio-myocardium sclerosis with implantation of cardiac pacemaker. Clinic history: On 26 January 2011 the patient arrived in our Diagnostic Vascular Ambulatory to perform arterial lower limbs colorduplex ultrasound for left pulsatile mass upper third of thigh, oedema left lower limb and reduced left extremity pulses. On color-duplex ultrasound was positive for a 4.5 9 5 cm mass with turbulent flow consistent with aneurysm supplied by probably artery/vein fistula. The angio CT-scan on the left iliac femoral artery did not show vascularization on the iliac artery but showed near PTFE iliac femoral bypass a fistula between superficial femoral artery and superficial femoral vein. About 5 cm under the fistula there was on the superficial femoral artery a big dilatation (Aneurysm? Venous dilatation?) and the iliac femoral by pass was completely obstructed by thromboembolic material. Clinical examination, laboratory and instrumental results: abdominal, neurological, superficial lymphatic examination and chest auscultation were normal. The cardiac tones also normal with rhythm induced by pace-maker. The peripheral pulses were reduced on the left lower limb. Fibrinogen 418 mg/dL (n.v. 200–400), ESR 83 mm h-1 (n.v. 3–46), CRP 34.4 mg/L (n.v. 0.0–0.5), iron 53 lg/dL (n.v. 60–150), ferritin 602 lg/L (n.v. 18–250), hematocrit 30.3% (n.v. 41–53%), MCV 102 fL (n.v. 80–99), haemoglobin 10.9 (n.v. 13.5–17.5), erythrocytes 3.160.000 (n.v. 4.50–5.90), GGT 112 U/L (n.v. 8–61), b2-microglobulin 3.64 mcg/mL (n.v. 0.80–2.20). White cell count, total protein, albumin, protein electrophoresis, coagulation test, renal function tests and urinalysis were normal. Hepatitis markers were negative. Chest x-ray, abdomen ultrasound, a cerebral CT-scan were normal. Clinical course: On the grounds of the color-coded duplex ultrasound is not possible to perform a correct diagnosis and also the angio CTscan is not clear regard to pulsatile mass. The true nature of mass has been discovered during surgical operation. The pulsatile mass was an aneurysm femoral artery with occlusive disease thrombosis of the synthetic graft also if the patient followed anticoagulant therapy with therapeutic range value. During the surgical operation there was removal of PTFE graft, the opening of the iliac artery, a new by-pass between common and peripheral femoral artery and by-pass between peripheral femoral and popliteal artery. During 2 days after surgical operation, vascularization of the left lower limb with the presence of peripheral pulses. On 3 days suddenly worsening with cold left lower limb and absence of peripheral pulses. For this reason a new surgical operation with transfemoral left amputation. Now the patient is still under study for difficulty to heal the surgical scare and for the rehabilitation to walk with prosthesis. Discussion and Conclusion: The aneurismal dilatation near the synthetic graft is a relative rare complication for damage to material of vascular prosthesis (chemical degradation, mechanical stress, damage of the fibres at the time of implantation) (1) (2), for trauma

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 (3), hypertension (with the case of the patient) that creates structural changes and several haemodynamic alterations with increased blood flow, flow velocity and parietal stress due to increased arterial diameters and/or intra-arterial pressure (4). Others causes of the aneurismal dilatation of/or near synthetic graft can be performed by: late perivascular inflammatory reactions after implantation of Dacron/ PTFE—covered endoprosthesis (5), thrombosis with aneurismal dilatation of the prosthesis segment for nonexpendable nature of Dacron/PTFE and its tendency to wrinkle. On the clinical presentation and on the vascular surgical operation has been formulated diagnosis of femoral aneurysm. This diagnosis is probably ascribed to the multiple surgical revascularizations that had created a parietal damage (with permanent weakened layers of arterial wall and thrombosis) near the synthetic graft. References 1. Khaira HS, Vohra H.: True aneurysm in a femoropopliteal dacron graft: case report and literature review. EJVES Extra. 2001;1:65–8 2. Illuminati G, Bertagni A. et al.: Faux anevrysme sur prothese en Dacron, vingt ans apre`s pontage aortofemoral. Ann Chir. 2001;126:783–5 3. Bilgehan Savas OZ, Ahmet Turan Yilmaz et al.: True aneurysm formation in axillofemoral bypass with a reinforced ePTFE graft. A case report. Vasc Endovasc Surg. 2002;36(4):327–9 4. Gerard M., Guerin AP, et al.: Large artery structure and function in Hypertension and end-stage renal disease. J Hypertension. 1998;16(12):1921–9 5. Scheinert D, Schroder M, et al.: Treatment of iliac artery aneurysms by percutaneous implantation of stent grafts. Circulation. 2000;102:253–8

Effect of a single oral dose of 600,000 IU of cholecalciferol on muscle strength in young women with vitamin D deficiency: a Prospective Intervention Study C. Cipriani, E. Romagnoli, E. D’Erasmo, A. Scarpiello, S. Russo, C. Castro, L. Lenge, R. Pilotto, J. Pepe, De F. Lucia, S. Minisola Department of Internal Medicine and Medical Disciplines, ‘‘Sapienza’’ University of Rome, Italy Purpose: The positive effects of vitamin D supplementation on muscle strength and tendency to fall is widely reported, particularly in the elderly. Few data are available in young people with low vitamin D status. Methods: Eighteen young women (mean age 32.1 ± 4.7 years, range 25–39; BMI 23.8 ± 4.01 kg/m2) with vitamin D deficiency received a single oral dose of 600,000 IU of cholecalciferol. Isometric grip strength of the upper dominant limb was evaluated using a hand held dynamometer (Kayser Italia s.r.l., Livorno, Italy). Maximal voluntary contraction force (MVC, Newton, N) and speed of contraction (S, Newton/second, N/s) were measured in the sitting position in each subject at baseline and at day (d) 3, 15, 30, 60 and 90. Serum 25(OH)D, ionized calcium (Ca++), phosphorus (P), PTH and 1,25(OH)2D were measured at each time point. Results: Mean MVC and S values did not change throughout the entire observation period. On the contrary, 25(OH)D levels significantly changed (p \ 0.001), with a rapid increase at d 3 (75.1 ± 16.6 ng/mL; p \ 0.001) and up to d 90 (31.7 ± 13.3; p \ 0.01), compared to baseline levels. A concomitant significant decrease in PTH concentration (p \ 0.01) was found, as soon as d 3 (-18.2 ± 15.3 pg/mL; p \ 0.001) and up to d 90 (-19.8 ± 12.9; p \ 0.001). A rapid increase in 1.25(OH)2D serum levels, at d 3 (96.6 ± 37.4 pg/ml, p \ 0.001) and up to d 60 (59.8 ± 28.8, p \ 0.05) was observed. Mean Ca++ levels did not change, whereas

S367 mean levels of P showed a significant increase at d 3 (3.8±0.6 mg/ dl, p \ 0.05). Furthermore, no significant correlation was found between both MVC and S with 25(OH)D, Ca++, PTH and 1.25(OH)2D levels at each time point. Interestingly, a positive significant correlation was found between both indices of muscle function and P levels at 60 d (MVC, r = 0.546 and S, r = 0.557, respectively; p \ 0.02 for both). Conclusion: A single huge dose of 600,000 IU of cholecalciferol is not effective in enhancing skeletal muscle strength in young women with vitamin D deficiency. This finding could be partly due to the small sample study, and/or the relatively short period of follow-up. Another possibility is that the effect is not picked up exploring this group of muscles. However, our results are in line with recent data demonstrating that the effect of vitamin D on skeletal muscle is probably indirect since vitamin D receptor are absent in this tissue. An increase of serum phosphate could be a possible link between vitamin D administration and improvement of muscle function.

Detection of Howell-Jolly body-containing erythrocytes by flow cytometric analysis: a new quantitative method to assess splenic function A. Di Sabatino, L. Brunetti, S. Calarota, C. Ubezio, R. Invernizzi, G. Carnevale Maffe’, M. Guerci, M. Tortorici, G.R. Corazza First Department of Medicine, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy Background and Aims: Several methods have been developed to quantify splenic function, including counting Howell-Jolly bodies (HJB) in a peripheral blood smear by using light microscopy; quantification of pitted erythrocytes, i.e. red cells with membrane abnormalities visible under interference phase microscopy as so-called ‘‘pits’’; and nuclear scans which investigate the splenic uptake of radiolabelled cells. However, all the above mentioned methods are burdened by a number of limitations: light microscope-HJB detection is semi-quantitative, it may be subject to observer-dependent variability, and is not useful in identifying mild degree of hyposplenism; pitted erythrocyte counting, though quantitative and accurate in identifying a mild hyposplenism, requires a specific microscope equipment (Nomarsky optics), which limits its widespread application in clinical practice, and it may be subject to observerdependent variability; nuclear scans require radioactive exposure as well as advanced technology which lessen its utility as a first-line method. Therefore, we here validated a new quantitative, non-observer-dependent method based on the detection of Howell-Jolly body-containing erythrocytes through flow cytometric analysis, which is a widely available technique. Patients and Methods: A peripheral blood sample was collected by 18 subjects who had had splenectomy and 20 age- and sex-matched healthy volunteers. Peripheral blood mononuclear cells were isolated through standard lympholyte gradient centrifugation, stained with FITC-conjugated anti-human CD71 (to detect reticulocytes), PEconjugated anti-human CD61 (to exclude platelets) and isotype control antibodies, and then analyzed by flow cytometry (FACScan, BD Bioscience) after addition of 1 ml cold TOPRO3 working solution. The percentage of CD71-negative/TOPRO3-positive represented the percentage of HJB-containing erythrocytes. One million events were acquired for each FACS tube. On the same samples, we also assessed the percentage of pitted erythrocytes. Briefly, two drops of fresh venous blood were mixed with 1 ml 3% buffered-glutaraldehyde solution, pH 7.4, in a vial. The fixed cells were examined in a wet preparation (magnification 9 1000) with a direct-interference contrast microscope (Leica Microsystems Wetzlar GmbH, equipped with Nomarski optics) by two operators. The percentage of pitted erythrocytes was then calculated (upper limit of normal = 4%).

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S368 Results: When we assessed splenic function through the gold standard method, i.e. pitted erythrocyte counting, as expected we found that all the splenectomized subjects had pitted erythrocyte values higher than 4% (median 15.8%, range 11.6–37.5), while all the healthy volunteers had pitted erythrocyte values lower than 4% (median 1.7%, 0.4–3.8). The median percentage of pitted erythrocytes was significantly higher in splenectomized individuals (p \ 0.0001) in comparison to healthy volunteers. When we used the new flow cytometric method, we observed that the percentage of HJB-containing erythrocytes was significantly (p \ 0.0001) higher (median 0.266%, range 0.038–6.692) in splenectomized subjects in comparison to healthy volunteers (median 0.052%, range 0–0.015). A significant positive correlation (rs = 0.583, p \ 0.0001) was found between the percentage of pitted erythrocytes and the percentage of HJB-containing erythrocytes in all the 38 subjects enrolled into the study. Conclusions: Our preliminary findings showing a very significant positive correlation between the classic pitted erythrocyte counting technique and the flow cytometric detection of HJB-containing erythrocytes suggest that the new method might represent a promising quantitative, non-observer-dependent tool in assessing splenic function. Further studies on series of hyposplenic patients are needed to verify whether this method might be useful in identifying mild degree of splenic hypofunction. Association between SNP rs1333040 on chromosome 9p21 and brain arteriovenous malformations I. Gatto*, A. Puca**, C.L. Sturiale**, A. Albanese**, G. Maira**, R. Pola* *Laboratory of Vascular Biology and Genetics, Department of Medicine, A. Gemelli University Hospital, Catholic University School of Medicine, Rome, Italy; **Institute of Neurosurgery, A. Gemelli University Hospital, Rome, Italy Introduction: Although single nucleotide polymorphisms (SNPs) of angiogenesis- and inflammation-related genes have been associated with sporadic brain arteriovenous malformations (BAVM), the exact genetic etiology of BAVM still needs to be elucidated. In the last 3 years, SNPs of chromosome 9p21 have been associated with various cerebrovascular diseases, such as stroke and intracranial aneurysms. The aim of this study was to test the association between one of the SNPs of chromosome 9p21 (rs1333040C[T) and sporadic BAVM in an Italian population. Methods: A blood sample was obtained from 52 BAVM patients and 63 unaffected controls. The SNP rs1333040C[T was genotyped and its frequency in cases was compared first with controls, and then with the European average rate (EAR), obtained from the ‘‘HapMap’’ project (6276 patients). SNP association with gender, age of clinical onset, cortical or deep localization, supra- or infra-tentorial localization, bleeding, nidus size, presence of deep venous drainage, perforator feeders, and epilepsy was also verified. Chi-square test established significant difference (p \ 0.05). Results: Genotypes frequencies in cases vs controls were: CC: 11.54 vs. 18.18% (p = 0.5038); CT 43.31 vs. 49.09% (p = 0.4601); TT 46.15 vs. 32.72% (p = 0.2210). Comparing SNP frequency between cases and EAR demonstrated a statistically significant association between the TT genotype and the presence of sporadic BAVM (p = 0.0115). None of the 3 genotypes showed association with sex, age of clinical onset, location, perforator feeders and bleeding. Nonmutated CC genotype was associated with superficial venous drainage (p = 0.0257), while the TT genotype was statistically significantly associated with BAVM nidi [4 cm (p = 0.0138). Conclusions: Genotype rs1333040TT on 9p21 might be associated with BAVM development and with susceptibility to larger dysplastic

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 nidi. The CDKN2A and B genes are located on chromosome 9p21. They encode the cyclin-dependent kinase inhibitors p16INK4a and p15INK4b, modulate the cell cycle, and regulate the p53. Their dysfunction has already been associated with oncogenesis and atherogenesis and might play also a role in the pathogenesis of BAVM.

Ground work of a program for primary prevention of cardiovascular diseases A. Gentile, V. Catozzo, G. Rinaldi, M.S. Del Prete, A. Balloni, W. Capeci, L. Falsetti1, N. Tarquinio, G. Filippi, G. Ciotti and F. Pellegrini Dipartimento di Medicina Interna ASUR ZT7 Ancona, Osp. ‘‘S.S. Benvenuto e Rocco’’ Osimo 1Medicina Interna, Malattie ImmunoAllergiche e Res, Medicina d’Urgenza, Ospedale Torrette, Ancona, Italy Background: Primary prevention represents the best treatment for CV diseases, in particular among high-risk patients. High levels of cardiorespiratory fitness were associated with an increase of the proven risk factors1 and a lower risk of having carotid atherosclerosis2. Moreover, among community dwelling, middle aged adults, a higher daily step count at 5 year follow-up than at baseline was associated with better insulin sensitivity. This effect seems to be largely mediated through lower adiposity, and time spent sedentary predicts higher levels of fasting insulin independent of the amount of time spent at moderate/vigorous intensity activity levels3,4. However, even among younger patients, reduction of CV-risk with physical activity, diet and other non-pharmacologic approaches is frequently underestimated. We started a project of in-hospital physical activity program for primary prevention among high-risk patients. Aims: To evaluate if a 3-months in-hospital course of physical activity can improve metabolic and vascular parameters in high-risk patients. Methods: We enrolled 24 consecutive, high-risk patients with no history of prior acute vascular events, defined as acute coronary syndromes, prior stroke/TIA and peripheral artery disease. For each patient we evaluated full history and drugs used. Each patients underwent to a complete evaluation before physical activity with treadmill stress-test, resting echocardiography, FMD, supra-aortic trunks with intima-media thickness (IMT) evaluation, fasting glucose/ insulin (HOMA index) and total cholesterol, LDL, HDL and triglyceride dosage. Patients with positive stress test were excluded from the training. After a three-months training (three times a week for an hour), we evaluated again the patients with the same tests done at enrollment. T-test for repeated measures and Wilcoxon’s sign rank test were used to assess differences among patients. Results: At baseline, patients had a mean age of 56 years, with a M:F ratio of 2:1, a mean weight of 100.5 kg (±4.70). 16.7% of the sample had smoke attitude, 83.3% were hypertensive, 58.3% had familial history of CV pathologies, 87.5% were diabetics. Mean BMI was estimated at 34.5 (±1.48) g/m2 with a mean Framingham risk score of 12% (13% corrected). Mean of HOMA index was 9.43 (±2.28); mean FMD was estimated at 12% (±2%); mean indexed left ventricle mass was estimated at 108 g/sqm (±7.4 g/sqm). At this moment, only 5 patients have completed 3-months course and are suitable for analysis. With paired-samples t-test we observed a significative reduction of BMI (2.6%, p \ 0.05), IMT (18%, p \ 0.05), HOMA-index (37%, p \ 0.05) and left ventricle mass (16.5%, p \ 0.05). We also observed a significative increase in vascular reactivity, as assessed with FMD (117%, p \ 0.05). Framingham risk score index decreased of 50% (p \ 0.05). Discussion: An in-hospital primary prevention can allow a safe reduction of CV risk among high-risk, obese patients. We observed a

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 reduction of global risk, as assessed with Framingham risk-score index, insulin resistance, endogenous NO production, carotid atherosclerosis and slight reversal of cardiac hypertrophy. These data represent a ground work to extend the program on larger cohorts. Conclusions: Primary prevention for CV diseases is based on reduction of modifiable risk factors, reducing individual risk. In addition to drugs, it is very important to change lifestyle. This highlights the importance of reducing sedentary time in order to improve metabolic health, possibly in addition to the benefits associated with a physically active lifestyle.

References 1. Payvandi L, et al. Physical activity during daily life and brachial artery flow-mediated dilation in peripheral arterial disease. Vasc Med. 2009;14(3):193–201 2. Physical fitness and carotid atherosclerosis in men. Lee CD et al. Int J Sports Med. 2009;30(9):672–6 (Epub 2009 Jun 30) 3. Objectively measured sedentary time may predict insulin resistance independent of moderate- and vigorous-intensity physical activity. Helmerhorst HJ, Wijndaele K, Brage S, Wareham NJ, Ekelund U. Diabetes. 2009;58:1776–9 4. Dwyer T, et al. Association of change in daily step count over five years with insulin sensitivity and adiposity: population based cohort study. BMJ. 2011;342:c7249. doi: 10.1136/bmj.c7249

Crucial role of PPAR-alpha in muscle regeneration I. Giarretta, V. Neri, I. Gatto, M. Palladino, R. Pola Dipartimento di Medicina Interna e Scienze Mediche Specialistiche, Universita` Cattolica del Sacro Cuore, Roma, Italy Peroxisome proliferator-activated receptors (PPARs) are ligandinduced nuclear receptors with important activities in regulation of glucose and lipid metabolism. In particular, PPARalpha and PPARgamma have an important clinical and therapeutic role. In fact, PPARa is activated by fibrates and its activity leads to lipid lowering. Recently, there has been increasing appreciation of the fact that, in addition to its lipid-lowering ability, PPARalpha is also involved in several other cellular mechanisms, including angiogenesis, improvement of tolerance to physical exercise, and reduction of oxidative stress. Based on these data, we hypothesized that PPARalpha may be important for the process underlying tissue regeneration after injury and performed experiments aimed to verify this hypothesis. Methods and Results: We used an established mouse model of injury and regeneration of the skeletal muscle, such as the cardiotoxin injury model. We used PPARalpha knockout (PPARa-/-) mice (8–10 week old) abd their appropriate and age-matched wild-type controls (Sv129 mice). The left tibialis anterior (TA) muscle was

S369 injured by an intramuscular injection of 100 microliters of cardiotoxin (CTX; Latoxan, Rosans, France), as established. Mice were sacrificed 10, 15, and 20 after CTX injury and both left and right TA muscles were dissected and used for the analysis of prototypical parameters of muscle regeneration and repair. First, we quantified the number of regenerating myofibers (identified by the presence of centrally-located nuclei) and found that, in PPARa-/- mice, the process of muscle regeneration was significantly delayed compared to wild-type controls. Indeed, while Sv129 mice had the highest number of regenerating myofibers at day 10 after injury and a very low number at day 20, in PPARa-/- mice, the highest number of regenerating fibers was observed at day 20, demonstrating that at this time-point the process of muscle regeneration was still ongoing. Then, we measured the sixe of the regenerating fibers and found that, in PPARa-/- mice, the average diameter of the regenerating fibers was significantly smaller than in wild-type controls. Finally, we quantified the extent of tissue fibrosis and inflammatory infiltrate and found that it was significantly larger in PPARa-/- mice, compared to controls. Conclusions: Our study suggests that efficient muscle regeneration dependent, at least in part, on PPARalpha signaling. This nuclear receptor might be a potential target for therapeutic interventions in subjects with muscle injury, dystrophy, and rhabdomyolysis.

A systematic approach for the prevention of falls in hospitalized patients G. Grignani, G. Mirandola*, E.E. Molteni, A. Sottocornola, M. Biffi**, M. Vanoli Department of Internal Medicine, *Risk Management, **Database Management; A.O. della Provincia di Lecco, Italy Falls are a public health problem worldwide. Older adults are more likely to fall and hospitalization increases fall rik because of the unfamiliar environment, illnesses and treatments. About 30% of falls in hospital result in physical injury. Falls may also lead to loss of function, anxiety, depression, impaired rehabilitation, increased length of hospital stay, and inability to return to previous residence, thus contributing to additional health and social care costs. Falls in institutions may sometimes result in complaints or litigation from families. ‘‘Reduce the risk of patient harm resulting from falls’’ is also one of the International Patient Safety Goals [IPSG.6] of the accreditation process by Joint Commission International. Fall risk assessment provides a baseline measure of risk status to guide actions able to reduce the risk of falling. To identify patients at higher risk for accidental falls, we prepared a simple flow-chart, partially based on the recommendations of the Guideline for the prevention of falls in older patients developed by a panel of the American Geriatrics Society (1). This flow- chart, filled out by nurses at admission to hospital, was aimed to select patients aged 65 years or older, able to walk, with: – a fall as the cause of the current admission to hospital, OR – two or more falls in the past 12 months, OR – one fall in the past 12 months and a positive Timed Up and Go Test (2). In this high-risk group, the following interventions were carried out: – a red plastic bracelet was put on the patient, to make the risk immediately evident to all the operators – a leaflet was delivered to the patient, his/her family and caregivers to inform about practical interventions to prevent falls – doctors made a written note of the risk in hospital records

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S370 – discontinuation or dose reduction of high-risk medications was considered. This protocol was applied to all the patients admitted to our Internal Medicine Department between October 1st and December 31st, 2010. A first step of our analysis was to evaluate the adherence to the protocol by nurses and doctors; a second step was to weigh its utility in fall prevention. We considered the hospital records of 218 patients, randomly chosen from the 442 subjects admitted to the Internal Medicine ward at Merate hospital in the above mentioned period. One hundred and nineteen (55%) were females; the median age was 79 years (range 18–101); 172 (79%) patients were aged 65 years or older. The flow-chart was present and correctly filled up by nurses in 206 cases (94%); 34 patients underwent the Timed Up and Go Test, which was positive for high risk in 82% of them. On the whole, 61 (28%) patients were identified as at high risk: in this group, a specific note was written by doctors in the hospital records in 55 cases (90%), together with therapy change(s), when indicated. The high proportion of properly filled out charts indicates that the approach we used is simple, quick to be learned and easy to manage at bedside. Only 3 falls were observed during this period in our series of patients (1 in the high-risk and 2 in the low-risk group), a number too small to draw any conclusion about the efficacy of our interventions. Therefore, we extended the analysis to include patients evaluated by the same flow-chart, admitted in the same period to the other wards of our Internal Medicine Department (i.e., Internal Medicine, Oncology, Nephrology, Infectious Diseases, and Dermatology, at Lecco hospital). On a whole of 627 patients randomly chosen out of 1473 admitted, 23 falls (3.6%) were observed during their hospital stay: 14 among the 154 patients identified as at high risk, and 9 among the 473 at low risk (Negative Predictive Value [NPV] 0.981). For ethical reasons we did not have a control group of patients identified as at high risk, but not treated with preventive actions. Thus, to evaluate the ability of our interventions in reducing falls, the comparison was made with our historical data (years 2007-2009), which had documented an already low frequency of falls (\3%). Apparently, our present results are merely in line with such a situation. However, historical data probably underestimated the real prevalence of falls, owing to the voluntary nature of fall reporting by operators, while the attention currently focused on falls and their registration has now markedly reduced this limitation. Therefore, we cannot rule out the possibility that our interventions were indeed able to reduce the actual frequency of falls, but that this effect has been masked by the expected increase in the number of reported falls. In any case, a systematic approach is the only way to obtain reliable data to monitor, which are useful to guide effective actions. Particularly in situations of low prevalence of falls, our flow-chart will be helpful in order to identify subjects at low risk, who need no further interventions, so permitting to focus attention and resources to the frailer, high-risk subgroup of patients. We are now testing an improved version of the flow-chart, in which two more aspects are being considered: the presence of difficulty with walking or balance, and the need of reassessing the risk at changes of the patient performance status during hospitalization. References 1. J Am Geriatr Soc. 2001;49:664–72 2. J Am Geriatr Soc. 1991;39:142–8

Unlucky holiday in Thailand G. Guerra, C. Delli Gatti, A. Zurlo Geriatrics Unit, Azienda Ospedaliero, Universitaria di Ferrara, Ferrara, Italy

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Aging is not disability and morbidity synonym, however it is a great risk factor for frailty and failure to thrive after a trigger event. A 90-year-old woman, in apparently good health, was admitted to the hospital complaining of nausea, asthenia, obstinate constipation and fever (temperature = 38C). The patient was just came back to Italy from Bangkok where, during her stay, was affected from gastroenteritis (fever, diarrhea, vomiting) treated with ciprofloxacin and symptomatic therapy with weak effect. The clinical history revealed hypercholesterolemia, trigeminal neuralgia, prior B hepatitis and prior cholecystectomy and appendectomy. Since a long time she has been treated with carbamazepine, rosuvastatin, acetylsalicylic acid. Findings from physical examination besides the fever showed only slight bilateral inspiratory crackles. The results of the rest of clinical examination were noncontributory. The white blood cell count was 18.6 9 103 uL, erythrocyte sedimentation rate 58 mm/h, C-reactive protein 19.6 mg/dL, fibrinogen level 800 mg/dL, sodium level 130 mEq/L. Chest X-ray revealed a left poor pleural effusion. Direct X-ray abdomen documented coprostasis of right colon with pneumatization and air-fluid levels of colon and small intestine. An aortic subdiaphragm thrombosed aneurysm of 10 cm was found from abdominal ecography. Therapy with intravenous levofloxacin (500 mg twice daily) was started with fever regression, but the abdominal symptoms got worse. The result of test for hepatitis A virus was reported to be positive suggesting an acute hepatitis. Computed tomography scan of the abdomen was performed and disclosed an aortic dissection of the thoracic aorta of wide size (12 9 6.5 9 10 cm diameter). The acute hepatitis A contraindicated the surgical operation in emergency. So it was postponed until acute hepatitis A was considered clinically solved. An aorto-aortic anastomosis was performed by surgery. In the post-operative phase patient moved to Intensive Unit where cardiorespiratory failure occurred. Few days later a chest X-ray revealed left pleural effusion increasing. Afterwords dysphagia and hyporexia occurred. A scapulary Herpes Zoster appeared in ninth post-operative day; two days later patient died. Successful aging is the goal of the geriatric medicine. Ninety people might be affected from uncommon age-related disease as well. Heedless and sweeping assessment of symptoms, general clinical condition and emergency situation comes out failure to thrive. ‘‘Ageism’’ restricts clinical behaviour, besides expected risks of invasive procedure.

The role of color Doppler ultrasound in diagnosis of Hodgkin’s lymphoma: a case report A. Iori, G. Troisi, A. Bellomo, C. Leboffe, V. Gianturco, E. D’Ottavio, V. Formosa, R. Frezza, M. Cirene, S. Bernardini, C. Lo Iacono, B. Marigliano, V. Marigliano Dipartimento di Scienze Cardiovascolari, Respiratorie, Nefrologiche e Geriatriche, Universita` Sapienza, Roma, Italy We report the case of a 29-year old men patient who came to our attention for weakness following a 4-day fever episode. The patient was negative for his previous medical history; his family history was positive for non-Hodghkin’s lymphoma. During the hospital stay, routine blood tests were performed. A leukocytosis was observed (13.010/lL, RR 4.000-10.000; lymphocytes 15.1%, RR 20-45; monocytes 11.1%, RR 2-10; neutrophils 9290/lL, RR 1.8-7.5). At protein electrophoresis, alpha1-proteins were 0.60 g/dl (v.n 0.210.35), alpha2 1.33 g/dl (v.n 0.51-0.85), beta1 0.65 (v.n 034 – 0.52), beta2 0.53 (v.n 0.23-0.47) and the ratio 1.05 (v.n 1.1-2.4). An abdominal ultrasound scan and a scan at the level of axillary, sovraclavear, cervical and inguinal regions were performed. Several

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 lymphadenopathies were observed at the level of the right laterocervical region (11 9 3 mm of diameter), the right and left sovraclavear areas (6 9 3 and 7 9 3 mm, respectively) and the left submandibular region (6 9 4 mm): in all the cases, the lymphnodes were roundish and poorly vascularized, with a poor representation of the hylar structures. Because of these results, a new ultrasound was required 3 months later. After 6 months, the patient returned to our observation. A new ultrasound was performed. Bilateral laterocervical (minor 10 mm), left sovraclavear (25 9 15 mm), and right axillary (more 21 9 18 mm) lymphadenopathies were observed, with a low representation of the hylar structures and a peri-intralesional vascularization. At the level of the axillary lymphadenopathy, an increased vascular index resistance (0.51 cm/s) was observed. The patient was admitted in our ward. A core biopsy of the right axillary lymphadenectomy was performed. At pathology, an Hodking lymphoma (classic sclerosing type) was detected (cell immunophenotype H/RS: CD30, CD 15 positive and CD 20 negative). In conclusion the vascularization score and pulsatility index are considered important indexes of malignity, useful for initial diagnosis of malignant lymphadenopathy. In particular, recent experiences have indicated that the contemporary evaluation of morphology and vascular structures may have an important role in the differential diagnosis of reactive and malignant lymphnodes. In fact, the tumor involvement of lymphnodes is usually characterized by their shape modification from oval to roundish, by hylar and cortical deformation and by neo-angiogenesis processes. In many works the authors confirm the possibility of differentiation of benign from malignant lesions of LN during estimation of the intranodal resistance (RI) – in LN malignant lesions the resistance index (RI) is usually over 0.8. Other authors consider RI over 0.72 as the indicator of the LN malignant lesion. So it is important deepen with cytological analysis a lymphadenopathy with vascularization intralesional whatever its index of resistance.

Prevalence of menstrual disorders and cardiovascular performance in athletes from different kinds of sports S. Lorini, L. Stefani, G. Beni, M. Dei, V. Bruni, G. Galanti Sports Medicine Center, University of Florence, Italy Introduction: The incidence of amenorrhea among the athletes is much grater observed than in sedentary, however the implication of this feature with the cardiovascular performance remain less clear. The study is aimed to investigate this aspect in a larger group of female athletes from sports at different static and dynamic component. Materials and Methods: Two groups of athletes 1Group (1G) aged 16±2, from swimming and dance at high dynamic and low static load and 2Group (2G) from volley-ball and gymnastic artistic at moderate/ high dynamic and static load, were submitted to a questionnaire to evaluate the prevalence of menstrual disorders and also to a Bioelectrical Impedance Analysis (BIA) and echocardiographic exam to verify the associated body composition and the morphological and functional heart pattern. Results: The menstrual disorders resulted to be generally low (13%) with an exclusive presence in the 2G. All the echo parameter were within the normal range in both groups without any significant variation with the exclusion of the Cardiac Mass Index(CMI) value that resulted to be significantly lower in the 2G respect of the 1G (Fig. 1). Otherwise the nutrition parameters showed a significant increase of the Fat Free Mass (FFM) in the 1G vs. the 2G. An inverse behavior (Fig. 2) was otherwise observed for the Fatty Mass (FM) values.

S371 Conclusions: The results support the hypothesis that the prevalence of the irregular menstrual cycle are independent from the nutritional parameters in sports at high-moderate dynamic component. An opposite trend is evident for the CMI that seems to be associated to a superior and more equilibrate body composition.

BIA Parameters 85 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 5 0

1G

0,04

2G 0,18

0,5 0,5

0,04 0,87

0,75

BMI

FFM

FM

TBW

ICW

ECW

PA

Spontaneous physical activity evaluation before to start with the exercise as prescription program G. Mascherini, L. Stefani, I. Scacciati, G. Galanti Sports Medicine Center, University of Florence, Italy Introduction: In subjects at high risk level, a correct investigation of the daily Spontaneous Physical Activity (SPA) as time, frequency, intensity and kind of exercise can play a relevant role to start with the ‘‘exercise as prescription’’ program The aim of the study is to evaluate, in a group of obese -hypertensive patients the real SPA at the beginning of the exercise as prescription by the accelerometer report.

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S372 Methods: the daily life style has been evaluated in a group of 30 obese –hypertensive patients (20 male and 10 female) aged 57.48±12.77 for 6 days by the accelerometer (AiperView 440) It has been positioned on the waist circumference of every subject analyzed. A PA more than 3 hours a weak represents the point to distinguish sedentary from active subjects, however several else parameters were analyzed: the Physical Activity Level (definite as EE/resting Energy Expenditure), medium daily distance and intensity of the PA expressed as slow (up to 3 km/h) or fast (up to 5/km/h) walk, and also the number of total daily steps. Results: The PAL (Physical Activity Level) observed was 1.57±0.16, medium daily distance was 6300.27±2525.15 m. The amount of time in 6 days spent as sedentary were 50±8.52 hours; the hours as exercise corresponding to 3 METS were 22.5±6.13, the time practicing exercise as 3-4.5 Mets was 11.23±3.89 hours, and the minutes spent for jogging were 72.41±80.67. The time of hours corresponding to the different degree of the daily PA were 8 hours 15 min sedentary, 3 hours 45 min slow walk, 1 hours 50 min fast walk. The number of the daily steps was around 9413.25±4003.12 in all the subjects analyzed. The daily calories spent were 889.5±272.02. Conclusions: The data obtained demonstrates the accelerometer can typify the intensity and the kind of exercise performed including information related to the SPA with a good definition of the LS. The identification of the presence moderate PAL in a group at high risk level, could therefore play a relevant role inducing to start with a ‘‘more adequate’’ PA program in these subjects balancing the moderate with intense exercises.

Staphylococcus lugdunensis endocarditis complicated by embolism in a 18-year-young woman with mitral valve prolapse: a good outcome of case

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Effect of an electronic nicotine delivery device (e-Cigarette) on smoking cessation and reduction: a prospective pilot study R. Polosa, P. Caponnetto. J.B. Morjaria, G. Papale, D. Campagna, C. Russo, P. Giovita Centro per la Prevenzione e Cura del Tabagismo (CPCT), Azienda Ospedaliero-Universitaria ‘‘Policlinico-Vittorio Emanuele’’, Universita` di Catania, Catania, Italy, Institute of Internal Medicine Background: Cigarette smoking is a tough addiction to break. Therefore, improved approaches to smoking cessation are necessary. The electronic-cigarette (e-Cigarette), a battery-powered electronic nicotine delivery device (ENDD) resembling a cigarette, may help smokers to remain abstinent during their quit attempt or to reduce cigarette consumption. The efficacy of these devices in smoking cessation and/or smoking reduction studies has never been investigated. Methods: In this prospective proof-of-concept study we monitored possible modifications in smoking habits of 40 smokers (unwilling to quit) experimenting the ‘Categoria’ e-Cigarette with a focus on smoking reduction and smoking abstinence. Study participants were invited to attend a total of five study visits: at baseline, week-4, week8, week-12 and week-24. Product use, number of cigarettes smoked, and exhaled carbon monoxide (eCO) levels were measured at each visit. Smoking reduction and abstinence rates were calculated. Adverse events and product preferences were also reviewed. Results: A mean of 2.0 cartridges/day was used at week-24. Sustained 50% reduction in the number of cig/day at week-24 was shown in 13/40(32.5%) participants; their median of 25 cigs/day decreased to 6 cigs/day (p\0.001). Sustained 80% reduction was shown in 5/40(12.5%) participants; their median 30 cigs/day decreased to 3 cigs/day (p=0.043). Sustained smoking abstinence at week-24 was observed in 9/40(22.5%) participants. Mouth (20,6%) and throat (32,4%) irritation, and dry cough (32,4%) were common, but diminished substantially by week-24. Participants’ perception and acceptance of the product was good. Conclusion: The use of e-Cigarette substantially decreased cigarette consumption without causing significant side effects in smokers not intending to quit (ClinicalTrials.gov number NCT01195597).

R. Pecoraro, A. Tuttolomondo, D. Di Raimondo, M. Pomilla, G. Parrinello, A. Pinto, G. Licata Dipartimento Biomedico di Medicina Interna e Specialistica, Universita` degli Studi di Palermo (Italy) Staphylococcus lugdunensis is a coagulase-negative staphylococcus (CNS). It is a major cause of prosthetic valve endocarditis, particularly during the initial years after valve surgery, an important cause of nosocomial infective endocarditis (IE), and the cause of 3 to 8 percent of native valve endocarditis, usually in the setting of prior valve abnormalities; among these, the mitral valve prolapsed (MVP) has emerged as a prominent predisposing structural cardiac abnormality. S. lugdunensis, who was first described in 1988, was distinguished from other coagulase-negative staphylococcal species via DNA relatedness studies based on 11 clinical strains. Like other CNS, S. lugdunensis in humans ranges from a harmless skin commensal to a life-threatening pathogen (as with infective endocarditis) but it is considered unique among CNS because of its propensity for causing aggressive native valve infective endocarditis (IE) often fatal and usually community acquired. We describe a case of Staphylococcus lugdunensis endocarditis in a 18-years-young woman with preexisting mitral valve prolapse in order to emphasize the aggressiveness, as documented in the scant literature yet available, of this staphylococcus who takes on virulence characteristics similar to Staphylococcus aureus.

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Pain characteristics in medical in-patient: an experience from a Medical Division F. Pomero, C. Brignone, E. Panero, M. Mellano, M. Galliasso, C. Serraino, E. Castagna, C. Bracco, S. Severini, A. Giraudo, L. Fenoglio S.C. Medicina Interna, ASO S. Croce e Carle, Cuneo, Italy Background: Pain has a prevalence of 40-90% in medical in-patients and its intensity is moderate to severe in 32-55% of cases (Numerical Rating Scale-NRSC4). Pain is treated in a very variable number of cases (28-79%). Chronic non-cancer pain (CNCP) is a particular category found quite commonly in Internal Medicine ward and has a 1-month prevalence of 19% in European adults, with important medical and social burdens. Objectives: We aimed to study the main characteristics of pain and how pain is treated in patients admitted in our Medical Division, ASO S.Croce e Carle, Cuneo. Methods: From 1st March to 30th April 2010 we included all the patients admitted in our ward with moderate- to-severe pain lasting at least from 24 hours; patients were excluded if they were not able to report symptoms. For each included patient we analyzed type, site, length, etiology (oncologic vs non oncologic), intensity (through

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 NRS) and treatment of pain. Pain was considered ‘‘chronic’’ if it had been lasting for C1 month. Results: Fifty patients were included, that’s means 20.8% of all admitted patients during the period of study. The mean age was 71±6.4 DS. Pain was the main cause of hospitalization in 54% of patients and was chronic in 50% of them (median length 70.4 days at the moment of hospitalization). Pain was not cancer-associated in 76% of cases; CNCP was present in 36% of the sample. Somatic and mixed pains were the most frequent types (54% and 28% respectively), while limbs and spine were the most prevalent sites (52% and 24% respectively). Pain was moderate (VAS 4-6) in 66% and severe (VAS 7-10) in 44% of cases. Considering oncologic pain and non-oncologic pain as separated categories, pain intensity was significantly more severe among the second one (NRS[7 22.8% vs 34.2%, p\0.05). Home-therapy was present in 48% of patients: more often NSAIDs or acetaminophen (30%), while opioids were already used in 12% of cases. Pain was treated in 94% of cases and relief was gained with acetaminophen, alone or combined with opioids, in 40% and with opioids in 48% of cases, with an whole prevalence of collateral effects of 24% (i.e. constipation, nausea/vomiting, sedation). Among patients with nononcologic pain, home-therapy was not present in 61.% of cases, pain relief was gained with acetaminophen, alone or combined with opioids, in 55.6% of cases, or with opioids in 22.2%; among oncologic pain home therapy was not present in 57.2% of cases and relief was got with acetaminophen alone in 28.6% and with opioids in 64.3%. Conclusion: One on five patients admitted in a Medical ward suffers from pain and in half of cases pain is the main cause of patient’s asking for hospital care. Neoplastic patients are increasing in Internal Medicine; nevertheless, in our experience pain is more frequent among non neoplastic patients, with one on three of these patients complaining for chronic pain and at least one on three of these patients having a severe pain. Up against that, opioids are often the effective therapy for cancer pain, while acetaminophen, alone or combined with opioids, is for non-cancer pain. Indeed, correct evaluation of pain in non-oncologic patients is of straightforward importance, as pain is very represented in this category, but could often be treated with wieldy drugs, as long as we have to find patients with severe pain in order to treat them with most effective therapy.

S373 complete evaluation of the aortic dimensions at root (AOr), LVDD (left ventricle diastolic diameter), LVSD (Left ventricle systolic diameter), IVS (interventricular septum), PW (posterior wall) thickness and LVMi (Left Ventricular Mass index) and EF %. Results: In athletes the LV dimensions and the LVMi were significantly higher than sedentary controls (LVMi : 123,45 vs 94,36 gr/m2 respectively). After five years follow up, the athletes didn’t show any modifications of the cardiac dimensions: Left Ventricular Diastolic diameter changes slightly from 52.00 ± mm to 52.90 ± mm; Left Ventricular Systolic diameter increased from 31.58 ± mm to 32.33 ± mm, Left Ventricular Mass index from 120.77 to 121.45 gr/m2; p=NS) and no significant enhancement of the aortic root diameter was observed (Aortic root: from 27.39 mm to 31.64 mm). Conclusions: In regularly trained athletes the LV dimensions chamber and LVMi are normally to the upper limits of the normal range. After a five -years -follow-up all the of cardiac chambers dimensions maintains anyway the same size with stable LVM values The regular physical exercise induces a mild LV hypertrophy. This increase of the of the LV chamber can be therefore considered a normal adaptive consequence to stress-exercise.

6 5 4 LVD

3

LVS

2 1 0 1

2

3

4

Fig. 1 Left ventricle diameters in athletes

11 10,5 10

Adaptive left ventricle hypertrophy in soccer players: a five years echocardiographic follow up

IVS

9,5

LW

9

L. Stefani, R. Mercuri, L. Toncelli, P. Manetti, A. Moretti, A. De Luca, G. Innocenti, V. Di Tantee, G. Galanti

8,5 8 1

Agenzia di Medicina dello Sport, AOUC Careggi, Universita` degli Studi di Firenze, Italy

2

3

4

yrs

Fig. 2 Wall thickness in athletes Background: Regular physical activity determines a progressive increase of the cardiac mass. It is an ‘‘Adaptive, Reversible and Physiological’’ hypertrophy whose Left Ventricle (LV) morphological aspect can be more concentric or eccentric in consequence of the type of sports practiced. No long term data are anyway now available in case of is a mixed training sport like soccer. The aim of the study was to follow up by the echocardiographic exam, the impact of the physical training on the heart morphology in a group of soccer players for at least five years. Method: Since January 1993 up to December 2005 a group of 220 athletes, playing in a Serie A Soccer team ACF Fiorentina, matched with a sedentary control group, were yearly followed by 2D echo-exam. The were regularly trained for 11 months a year, for at least 2 hours for five times in a week and they played a match on the Sunday. In the month of July the players made a stage of 3 weeks of 2 sessions of training including 2–3 hours daily. Among them, 46 athletes had a full 5 years echo-follow up with a

130 127 124 121 118 L 115 112 V 109 Mi 106 103 100 97 94 91 88 85

LVMi ath LVMi sed.

1

2

3 yrs

4

5

Fig. 3 Left ventricular indexed mass in athletes and sedentary subjects

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Efficacy and educational role of a daily employment of the accelerometer to improve the life style in overweighthypertensive population L. Stefani, G. Mascherini, I. Scacciati, G. Galanti Sports Medicine Center, University of Florence, Italy Introduction: The daily evaluation of the life style is fundamental to establish the amount of the ‘‘physical activity as therapy’’ to reduce the cardiovascular risk. In addition to a simple questionnaire, a long period registration by an accelerometer can be helpful to identify active from inactive subjects. The aim of the present study is to verify, in a small cohort of subjects at high risk level (obese–hypertensive), the health outcomes. Materials and Methods: 22 subjects (15 male, 7 female) were evaluated by the questionnaire and also by an accelerometer positioned on belt for 5 days to establish the daily Physical Activity Level (PAL) distinguished as low walking, fast walking, jogging. The anthropometrics parameters, including Body Mass Index (BMI), Waist Circumference (WC), Hip Circumference (HC) and body compositions parameters like Fat Mass (FM), Free Fat Mass (FFM), Total Body – Intracellular and Extracellular Water (TBW, ICW, ECW) and Phase Angle (PA) were measured at the beginning (T0) and after 3 months (T3) of exercise. The amount of the exercise prescribed for 3 months and at least 3 times in a weak, was determined by the Cardiopulmonary test parameters using the formula evaluating the max HR corresponding to the 60% of the VO2. Statistical analysis included T-Student test for paired data with a significance at P \ 0.05 value. Results: Respect of the questionnaire the accelerometer report showed a predominantly inactive life style (PAL=1.49±0.13). After three months of exercise, the BMI was significantly reduced (T0 = 29.61 ± 9.11; T3 = 28.8±8.89) in all (P \ 0.05). A trend toward a reduction was observed for FM (T0 = 26.23 ± 10.5 kg; T3 = 23.08 ± 8.03 kg), for the WC (T0 = 102 ± 13 cm; T3 = 93.63 ± 15 cm) the HC (T0 = 106 ± 7 cm; T3 = 101.2 ± 2 cm) the TBW (T0=49.3±9.0 l; T3=41.36 ±9.46 l) and ICW (T0=23.91±6.25 l; T3=22.90±6.16 l) while the PA maintained the values within the normal range (T0=7.84±1,4; T3=6.48±1.23). A significant variation was on the contrary observed among the values of the ratio TBW/ECW (T0= 2,41[T3=2.24; P\0.05). Conclusions: The employment of the accelerometer is associated with an improvement of those parameters strongly related with the cardiovascular risk. The results obtained support the educational role of the accelerometer in subjects at high risk level.

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Severe febrile illness in multiply transfused, splenectomized young: PUBMED-guided salvage treatment with ganciclovir D. Torres, R. Marrone, M. Pomilla, V. Siragusa, M. Bellanca, G. Parrinello, G. Licata Dipartimento Biomedico di Medicina Interna e Specialistica. Universita` di Palermo, Palermo, Italy A 23-years old smoker men was admitted for about 12 days history of moderate fever (prevalently serotin) associated with cough, sputum and mialgias. At home, he was treated with various antibiotics without benefit. Because his clinical conditions progressively worsened, he was hospitalized. On admission, no other clinical signs/ symptoms accompanied the syndrome and a marked leukocytosis (35.000/ll, count could not be determined in the first two days) was found. H1N1 infection was rapidly excluded and chest X-Ray was normal. During hospitalization fever became high and he developed hypoalbuminemia and a nephritic-nephrotic syndrome with typical edema. The remittent febrile profile and leukocytosis oriented for bacterial sepsis (as confirmed by an orthopantomography positive for dental abscesses) and a prolonged course (10 days) of intravenous treatment with a multiple association of antibiotics at large spectrum was started on admission. Ultrasound and TC of abdomen showed mild epato-splenomegaly and excluded mass and infective foci. However, antibiotics did not resolve the syndrome which became rampant: general clinical conditions and facial and limb edema rapidly worsened. Peripheral smear showed neutrophilia, lymphocytosis and atypical lymphocytes. Laboratory test excluded HIV and the main bacterial infections; emocoltures were always negative. The only positivity (mild) was found for CMV serology. On these basis, we reevaluate the case and concluded to exclude leukemias/lymphomas and viral infections. At first, we pose attention to a particularity of the history: 10 months before he was splenectomized and multiply transfused after a severe polytrauma on the road. We did a medline on pubmed with the following keywords: fever, splenectomized, transfused. We found few article concerning severe CMV infection or reactivation in this splenectomized, transfused, trauma subjects. For this reason and in consideration of the very severe clinical conditions, we immediately started a salvage treatment with intravenous ganciclovir. This therapy was following by a rapid and stable defervescence in two days with fast improvement in clinical conditions, cenesthesis and white blood count. The patient was discharged after 8 days in a good clinical general health. After one-year he was very well. This observation suggests: 1. Splenectomy changed the immunological defense against the virus and brought the infection to nearly fulminant scale; 2. Clinical history is very determinant to the decision making process in cases of severe febrile illness; 3. PubMed is a special weapon of the internist to manage difficult cases.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 A rare cause of epilepsy in a young patient P.F. Zamboni, M. Massari, P. Grossi, M. Tampieri, G. Bellodi, S. Guarino, V. Mazzini, A. La Froscia, L. Lenzi, A. Arcadi*, S. Prearo**, P. Gruppillo U. O. Coordinamento ed Integrazione Attivita` Mediche e Specialistiche; *M. O. Lungodegenza, Ospedale di Argenta, AUSL di Ferrara. **Sede Provinciale INPS, Ferrara, Italy Tuberous sclerosis is a systemic hamartomatous disease that affects central nervous system, skin, heart, eyes, kidneys, lungs and skeleton. Typically occurs with: epilepsy, mental retardation and skin lesions; the prevalence is 4-10 patients/100000 inhabitants. A 17 years old Pakistani male came to observation because of the appearance, since a week, of repeated tonic-clonic epileptic seizures. History: since the age of 8 years he presented epileptic seizures and he has been treated with carbamazepine 200 mg/day; at the age of 10 years he presented mental retardation (I. Q. 48). Cardiac, thoracic, abdominal, neurological, skin and fundus oculi examination: normal. Routine blood tests: normal: Hb, WBC, platelets, ESR, glucose, creatinine, sodium, potassium, calcium, AST, ALT, bilirubin, total protein, FT4 and TSH; carbamazepine 2.6-9.7 lg/ml; negative: IDA test and Toxoplasma IgM and IgG. ECG and chest x-ray: normal. EEG: bilateral slow anomalies in the absence of any epileptiform significance. CT brain: calcified round formation of 9 mm in diameter, in the right semioval center; distal to this, serpiginous calcified formation with radial course, more than 2 cm in extension (arteriovenous malformation? outcomes of parasites?). MRI brain: findings consistent with the context of tuberous sclerosis. During the hospitalization the appropriate dose of carbamazepine has been fixed: 200 mg 3 times/day; in the first days of hospitalization, because of recurrence of tonic-clonic epileptic seizures, he has been treated with intravenous diazepam; he had some seizures without the characteristics of epilepsy too, but of hysterical type. At discharge the patient had no epileptic seizures since 5 days and he was assigned to neurologic and psychiatric day hospital for the next follow-up. When foreign patients, coming from developing countries, are admitted to departments of internal medicine, they might have rare diseases previously not recognized; the task of specialist in internal medicine is to make a correct diagnosis and a subsequent follow-up, with the help of competences of other specialists. Our patient presented some typical features of tuberous sclerosis: epilepsy, mental retardation and brain MRI image; while, at the time of admission, were not involved other organs, the skin in particular; among symptoms to point out hysterical seizures, with different characteristics from epilepsy.

Nephrology

Acute portal and superior mesenteric veins thrombosis in nephrotic syndrome associated with acute hepatitis S. Caravita*, F. Rastelli**, E. Corghi**, C. Sarcina**, L. Buzzi**, R. Raiteri***, S.C. Wu*, M.B. Secchi* *U.O.C. Medicina Interna, **U.O.C. Nefrologia; ***U.O.C. Radiologia, Ospedale Bassini, Azienda Ospedaliera Istituti Clinici di Perfezionamento, Milano, Italy Introduction: It’s well known that nephrotic syndrome is characterized by a hypercoagulable state, and that common but serious complications of this disease are represented by thromboembolic

S375 events. The most frequent sites of thrombosis during adult nephrotic syndrome are deep veins of lower limbs and renal veins. Here we describe a case of portal and superior mesenteric veins thrombosis in a diabetic patient with secondary nephrotic syndrome. Case report: A 70-years-old man was admitted to our Emergency Room having experienced abdominal pain, nausea, vomiting, diarrhea and progressive deterioration of general conditions. 7 days before he had been discharged from another hospital where a definitive pacemaker was implanted for second-degree atrio-ventricular block. His past medical history included diabetes mellitus diagnosed 40 years before and arterial hypertension. His current medical therapy consisted of: repaglinide 2 mg TID, metformin 500 mg BID; irbesartan 300 mg/hydrochlorothiazide 12,5 mg; lacidipine 20 mg; acetylsalicylic acid 100 mg. Physical examination on admission revealed: a blood pressure of 100/60 mmHg, a heart rate of 110 beat per minute, an oxygen saturation of 92% while breathing in room air, a respiratory rate of 30/minute, normal body temperature; there were lung rales at the lower lung lobes, jugular distension, and bilateral edema of the lower limbs. Initial laboratory data showed: serum creatinine 3.28 mg/dl (normal values 0.67-1.17); urea 230 mg/dl (0-50); sodium 137 mmol/ L (136-145); potassium 6.9 mmol/L (3.4-4.8); aspartate aminotransferase 4236 UI/L (0-40); alanine aminotransferase 4373 UI/L (0-41); total bilirubin 1 mg/dl (0-1.2); glucose 186 mg/dl (60-110); C-reactive protein 7.88 mg/dl (0-0.5); prothrombin time 35% (70-120), INR 2.01 (0.85-1.2); partial thromboplastin time 36 s (21-36), ratio 1.24 (0.8-1.25); white blood cells count 14.129 109/L; Hb 10.8 g/dl; platelet count 266x109/L. Electrocardiogram showed normal pacemaker rhythm; chest x-ray showed pulmonary edema. Arterial blood gas analysis showed metabolic acidosis with hypoxemia. After initial treatment, consisting in: oxygen, furosemide, and bicarbonate, the patient was admitted to the Nephrology Ward. Further laboratory investigation showed proteinuria in the nephrotic range (3.5 g/L) with serum albumin of 2.73 g/dl (4.48-5.28). An abdominal ultrasonography performed during the first day of hospital stay revealed mild hepatomegaly, mild ectasia of inferior vena cava and suprahepatic veins, portal vein of normal diameter with thrombosis of the hilar tract; kidney parenchyma slightly thinned with a markedly hyperechoic cortex; there was no ascites. An abdominal CT confirmed the portal vein thrombosis at the hepatic hilus, showing also thrombosis of the mesenteric vein. Therapy with intravenous unfractionated heparin was started initially, then substituted with subcutaneous low molecular weight heparin. Extensive laboratory tests for infective, autoimmune, neoplastic diseases and for thrombophilia were all negative. With the observed improvement of hemodynamic status and of renal function and taking into account a troponin T value of 957 pg/ml (0-14) and a CK-MB value of 8.94 (0-4.94), a coronary angiography was performed, revealing a severe 3-vessel coronary artery disease, not amenable of percutaneous or surgical revascularization; clopidogrel was added to the treatment schedule. The patient was discharged from the hospital with a creatinine of 1.7 mg/dl, a proteinuria of 1 g/L, and a therapeutic regimen including acetylsalicylic acid 100 mg, clopidogrel 75 mg, ramipril 2.5 mg, furosemide 25 mg BID, bisoprolol 2.5 mg, enoxaparin 6000 BID, 5-mononitrate 20 mg TID, simvastatin 40 mg, insulin. Normalization of hepatic transaminases was observed after 1 month and complete recanalization of portal and mesenteric veins after 2 months. Conclusions: (1) the diagnosis of acute portal and superior mesenteric veins thrombosis should be considered in nephrotic patients even if it is has been rarely reported; (2) anticoagulant therapy should be started soon after ultrasonography or CT findings, as suggested by some Authors, to obtain the maximum benefit; (3) we think that in our case, mainly hypovolemia was the risk factor predisposing to thrombosis, while we can’t explain univocally the significant elevation of transaminases observed at the presentation.

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S376 Role of renal artery resistive index in SLE nephritis F. Ceccarelli, A. Gigante, F. Borghesi, R. Renzulli, F.R. Spinelli, C. Perricone, R. Cianci, F. Conti Dipartimenti di: 1Medicina Interna e Specialita` Mediche, Reumatologia, e 2Medicina; Clinica, Sapienza Universita` di Roma, Italy Background: Despite that renal involvement is a frequent feature of patients affected by Systemic Lupus Erythematosus (SLE), only few studies evaluated the association between intrarenal arterial resistive index (RI) and vascular or tubule-interstitial changes in the kidney, showing contrasting results. Objectives: We aimed at evaluating the correlation between intrarenal arterial RI, by means of color Doppler ultrasonography (US), and histological features of patients with SLE who underwent renal biopsy. Secondary objective was to perform a correlation between the RI and the functional renal indices. Patients and Methods: Consecutive patients affected by SLE according with revised American College of Rheumatology (ACR) 1997 criteria, candidate to kidney biopsy because of the renal involvement, were enrolled. The functional renal assessment was obtained in all the patients (serum creatinine and blood urea nitrogen (BUN) levels, quantification of urinary protein excretion in 24 h). The kidney biopsy was performed according with standard procedures, and the class of nephritis was assessed according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2004 classification. The presence of arteriolosclerosis was registered with the application of a semiquantitative score ranging from 0 to 3 (0=absent, 1=mild, 2=moderate, 3=severe). Color-Doppler US evaluation of intrarenal arterial RI was performed on the same day of kidney biopsy. Results: Thirty-four SLE patients (M/F 2/32, mean age 33.3±11.1 years, mean disease duration 130.5±94.8 months) were enrolled. Mean ± standard deviation (SD) creatinine level was 1.4±1.2 mg/dl, BUN 41.2±42.9 mg/dl, proteinuria 2.4±2.2 g/24 h. Nineteen patients (55.9%) had hematuria. Six patients (17.6%) showed class II nephropathy, 10 (29.4%) class III, 15 (44.1%) class IV, and 3 (8.9%) class V. Histological evaluation found arteriolosclerosis in 10 (29.4%) patients (score=1 in 1 pt, score=2 in 7 pts and score=3 in 2 pts).m Mean ± SD RI was 0.65±0.07, RI[0.8 was measured only in 2 patients (5.8%). The RI showed a significant correlation with creatinine levels (p=0.006) and BUN levels (p=0.001). No correlations were found with the presence of proteinuria or hematuria. Subgrouping the patients according to nephritis class, no significant differences were found in RI. Nonetheless, a trend showing higher mean RI in patients with class III and IV was observed, and the 2 patients with RI\0.8 had both class IV nephropathy. No statistical differences were found in mean RI subgrouping the patients according to the presence of arteriolosclerosis. Conclusion: In our study we found a significant correlation between renal arterial RI, evaluated by means of color-Doppler US, and renal functional parameters, specifically creatinine and BUN levels. No correlations were found with the histopathologic WHO classes, however, due to the relatively small cohort, we cannot draw definitive conclusions. Further investigations with lager cohorts are required to better address this issue.

Kidney function in consecutive patients admitted to an Internal Medicine Unit A. Conca, D. Spinelli, F. Minonzio, C. Hu, G. Spoletini, F. Cantoni, G. Fabio, M.D. Cappellini UO Medicina Interna 1 A, Fondazione IRCCS Ca` Granda Ospedale Maggiore Policlinico, Milano, Italy

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Kidney function abnormalities are very common in patients admitted to internal medicine units; however specific studies are lacking. This is a study on renal function in 131 consecutive patients (mean age 73 yrs, 66 females, 65 males) admitted to Medicina Interna 1A Policlinico Foundation in Milan from November 2010 to May 2011. In order to evaluate the kidney status and to identify possible causes of the acute or chronic renal dysfunction we collected informations on prevalent comorbidities known to be responsible for kidney function impairment (such as diabetes and hypertension), and we evaluated renal serum chemistry panel, urine analysis/dipstick findings and a subset of serum electrolytes. Furtherly, informations about ongoing drug therapy were collected. Whenever available, we’ve taken into account the yield of recent renal imaging studies (ultrasound or CT of the abdomen). 131 consecutive patients were enrolled in the study. We found 49/131 (37%) patients with chronic renal failure (CRF, estimated glomerular filtration rate [eGFR] \60 ml/min/1.73 m2 plus evidence of parenchymal kidney damage or a positive history for the presence of risk factors for the progression of renal disease). In deeper detail, as shown by our data, 38 pts (29% of total, mean age 70) had normal renal function. Among the 44 patients with chronic kidney disease (CKD) stage 1 and 2 (eGFR C 60 ml/min/ 1.73 m2 but evidence of parenchymal kidney damage) 12 pts (9% of total, mean age 72 years) had possible glomerular proteinuria and 32 (24% of total, mean age 73 years) had an imaging study positive mainly for scleroatrophic, cystic and stress bladder diverticular disease. In this subgroup principal risk factors for CKD were diabetes mellitus (DM, 8/44 pts, 18%), systemic arterial hypertension (24 pts, 55%), some kind of damage from atherosclerotic disease (15 pts, 34%) such as coronary artery disease (CAD), cerebral vascular disease (CVD), peripheral artery disease (PAD) and related risk factors (hypercholesterolemia in 12 [27%] and smoking in 21 [48%] pts), benign prostatic hyperplasia (BPH) and other forms of bladder outflow obstruction (8 pts, 18%) and presence of an M component on serum protein electrophoresis (SPEP, 4 pts, 9%); Phosphorus (Pi) and corrected total calcium (Ca) were within normal range. Mild CRF (CKD stage 3) was present in 41 pts (33% of total, mean age 75 yrs) with the following distribution of risk factors: DM (13/41 pts, 32%), hypertension (25 pts, 61%), overt atherosclerotic disease (14 pts, 34%), hypercholesterolemia (6 pts, 15%), smoking (17 pts, 41%), positive family history for early acute cardiovascular event (3 pts, 7%), BPH (3 pts, 7%) and M component (3 pts, 7%). Available imaging showed scleroatrophic (9 pts, 22%), cystic (12 pts, 29%), urolithiasis (3 pts, 7%), high intraparenchymal blood flow resistance (2 pts, 5%) and significant renal artery stenosis (1 pt, 2%); one pt was nephrectomized and another had heterotopic kidney transplantation. Again, Pi and Ca were within limits of normal. Six pts (5% of total, mean age 75 yrs, 2 nephrectomized) had CKD stage 4; none had hypercholesterolemia or a SPEP positive for M component; hydronephrosis adds to other typical radiologic findings in this cohort and average Pi is 5.0 mg/dl (upper limit of normal) with Ca still within normal range. ESRD was present in 2 pts (one had severe cardiovascular disease, proteinuria and Pi and Ca at the limits of normal; the other was on hemodialysis, had proteinuria and severe complications from DM/systemic atherosclerosis). Even more interesting was observing a high prevalence on admission of hyponatremia (32 pts, 24% of total, mean age 76 yrs) in the setting of inappropriately high calculated urine osmolality and, to an even greater extent, a BUN/SCr value C 20, as in prerenal azotemia (129/131 pts). Both of them possibly result from a tendency to chronic renal hypoperfusion which might depend on age associated hydroelectrolytic borderline status (to the limit of desalination/dehydration) and other comorbidities: the latter varies little on discharge (4% only), after the possible hypercatabolic state associated to acute phase response on admission should have been corrected. Serum potassium was out of

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 range on admission in 26 pts (20% of total): all of them had a mild CKD which doesn’t explain this finding by itself. Most of patients (71, 54% of total) had anemia of different degrees which was normocytic: for them mean eGFR was slightly higher than 60 ml/min/1.73 m2 and mild CKD could contribute to the low Hb levels (we can’t say that for sure with data available). If we define acute renal failure (ARF) as a rapid rise in value of SCr of 1.0 mg/dl or more, almost 1 out of 10 patients had ARF on admission or developed it during his or her hospital stay. Prerenal etiology was by far the most common and often due to severe dehydration with consequent loss of left ventricular preload and effective arterial blood volume.

Oncology An insidious case report of chest pain L. Castorani, A. Belfiore, G. Davanzante, A. Mele, S. Pugliese, G. Palasciano Clinica Medica ‘‘A. Murri’’ Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, Bari, Italy A 71 year old man has come to our attention from the emergency room of our hospital with the diagnosis of ‘‘chest pain’’. The patient has reported the onset of hoarseness for a few days, a pain in the precordial and right arm, accentuated by finger pressure and acts of breath (especially with deep inspiration). The cardiac and abdominal examination have revealed no pathological changes, whereas in the respiratory tract we have noticed a harsh vesicular breath sounds throughout the lung field. The patient has also shown mainly dysphagia for liquid food. The first biochemical investigations (indices of myocardial necrosis: troponin and myoglobin) and instrumental (ECG and echocardiogram) have excluded a pain of cardiac origin. The other biochemical tests (renal, hepatic, coagulation, serum electrolytes) were normal. The patient, in November 2009, performed various investigations for some diffuse arthralgias. The diagnosis was osteoporosis and osteoarthritis of the spine in the dorsal and lumbar tract. Twenty days before he had been hospitalized for the same symptoms and was discharged with a diagnosis of ‘‘atypical chest pain, ischemic heart disease, hypertension, osteoporosis’’. Because of the pulmonary objectivity we have decided to do an x-ray chest (RX 2p), which has shown a slight thickening in small pulmonary right middle field. At this point we have made the following the diagnostic hypotheses: (1) lung cancer, (2) paraneoplastic syndrome, (3) neurological disease, (4) aspiration pneumonia. Given the outcome of the RX exam we have performed a CT head and chest with contrast agent reporting that ‘‘in the anterior segment of upper lobe there is a clearly solid formation in nodular spiculated margins of the maximum diameter of about 2 cm probable nature of heterologous. Also, there are frosted-glass areas in the sub-mantle in the ipsilateral lower lobe. There are enlarged lymph nodes in the superior mediastinum, in lodge Barety, in the epi-aortic, aorto-pulmonary window and in the precarenale, maximum diameter of 15 mm’’. Among the tumor markers there is an increase of the tissue peptide antigen: 111 U/l with normal values between 0 and 77. For dysphagia and dysphonia we have performed a neurological consultation which underlines the absence of gag reflex bilaterally, without clinical involvement of other cranial and spinal nerves. The patient has also carried on an X-ray esophageal Gastrografin that has reported: ‘‘uncoordinated motor pharyngooesophageal in patients with accumulation of fluid in the esophagus and regular emptying of the esophagus. The motor incoordination determines inhalation of the contrast agent with partial painting of the main bronchus the left and the terminal bronchioles’’. In suspicion of a multineurite we have also performed a lumbar puncture. Analysis of

S377 liquor cerebrospinalis (CSF) showed an intrathecal synthesis of oligoclonal immunoglobulin G. CSF are carried out numerous investigations on all of them proved negative: Treponema pallidum Haemoagglutination Assay (TPHA) and Veneral Disease Research Laboratory (VDRL), search for bacteria, viruses and mycetes, WidalWright serodiagnosis and cytology. All autoantibodies were assayed absent (anti nuclear antibodies, antibodies to extractable nuclear antigens, anti neutrophil cytoplasmic antibody, anti-double-stranded DNA antibodies, anti-transglutaminase antibodies, anti endomysium antibodies, autoantibodies against voltage-gated calcium channels). For the suspected diagnosis of lung cancer with paraneoplastic myasthenic syndrome the patient has undergone bronchoscopy. The cytological diagnosis and the search for mycobacteria in bronchial lavage fluid was negative. Together with the colleagues in thoracic surgery we have decided, then, to perform a needle aspiration of the nodule of the upper lobe of the lung and lymph nodes. The histological report says: ‘‘issues with mucinous adenocarcinoma (extracellular), lymph node metastasis of adenocarcinoma’’. The patient has also made a PET scan that shows multiple areas of high metabolism to relate in neoplastic tissue. He was discharged with a diagnosis of ‘‘pulmonary adenocarcinoma with lymph node and bone metastases’’. He has been assigned to oncologists for chemotherapy. A year and a half after diagnosis, the patient died of the extensive neoplastic involvement.

Necessity of continuity in communication with oncologic patients L. Cifaldi, G. Cristina, R. Gareri, E. Capomolla, M.A. Ricciotti, I. Benedetti, B. Gullo, G. Montemurro, V. Felicetti U.O.C. Oncologia Medica, Azienda USL RM G, Ospedale Parodi Delfino Colleferro, Rome, Italy Introduction: The following research comes as a consequence of the fact that in some circumstance oncologic patients (OP) need to confront their selves not only with their specific ward, but also with other wards, that receives patients with oncologic disease and patients with other kind of pathologies. The patient needs to follow a healing procedure that brings him/her to relate to different hospital departments where the welcome and the care to communication is a key factor to demonstrate to the sufferer the continuity in his/her cure. Considering the World Health Organization’s recommendations, which look at every aspect of the sick person’s life and consequently also the psychological and relational ones, we tried to investigate the experiences of oncologic patients in throughout all hospital departments, to highlight the benefits or the critics to the communication perceived in the wards. Starting from a Costumer Care Interview data analysis, which has been submitted for years at the Medical Oncology Unit of Colleferro Hospital it was interesting to survey the experience of some patients from other wards, to acquire useful elements to improve patient experience in all hospital areas as well as the wards cooperation. Objective: The purpose of the survey is to gain the OPs perception of the communication they have received during their hospitalization, by asking them questions aimed at inquire the state of their permanence in other hospital wards. The goal is to remark their needs, improve the team work form different in wards and focus the attention on specific needs of people affected by neoplastic disease. Patients and Methods: Outpatients with solid tumor receiving adjuvant or metastatic treatment were evaluated for clinical condition and psychic condition. The quality of the perceived communication was explored by the evaluation of the different experimented hospitalization situations. We used a short questionnaire about the following area of interest: 1) quality of assistance; 2) needs; 3) health

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S378 communication; 4) continuity of communication. All patients met the criterion of awareness about their disease. Results: 14 out 210 patients (10 males, 4 females; age 66.4±9 years) who received a treatment for neoplastic diseases and had a hospitalization voluntarily partook and returned the questionnaire examining patients’ experiences. We can see that most of them are completely satisfied by the quality of the medical assistance. Only 4 patients, reported a total dissatisfaction with the health communication received during their entire hospital stay. With regards to the continuity of the communication between the wards, patients are completely satisfied. Discussion: In conclusion is interesting to remark for OPs, the communication between wards is decisive to maintain an emotional balance and feel supported while treated for their disease. Most OPs need constant and detailed explanations about the state of the disease and about potential side effects of the treatment. The qualitative level of the communication which is carried in one ward must be the same in the whole hospital, especially in those wards that have in charge the same patients. OP requires a continuity in communication throughout the oncological treatment. From this point of view the survey performed could be considered as a preliminary approach to this specific area of studies, and is part of those considerations that brought to life a new professional: ‘‘The Medical Oncologist’’.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Orthodox). For 37 CPs it was simple to fill in SOS and for 3 CPs it was a little difficult; 7 out 40 CPs asked to fill out with the help of a doctor or a family member. The educational level did not interfere with the filling in SOS. Spiritual life of 25 CPs changed during the course of the disease, increasing in 17 CPs and decreasing in 8 CPs. All CPs felt that health care should also consider spirituality to improve the quality of care (5=a little; 26=considerably; 9=very much). Discussion: Our preliminary data suggest that SOS can be a helpful clinical tool for the proper identification of spiritual needs and resource in CPs. SOS can detect and in part measure the symptoms of a need. The satisfaction of needs improves the perceived quality of care, allowing to the definition and implementation of specific actions. Routine inquiry about spirituality should be incorporated into the initial or interim clinical history to improve CP’s knowledge. The properly modified SOS-questionnaire could also be used in a setting of non-cancer patients with chronic and degenerative diseases, to evaluate the intersection of spirituality with health care.

Has the duration of symptoms before diagnosis a prognostic value in pancreatic cancer? P.G. Gobbi, M. Bergonzi, L. Villano, D. Pozzoli, G.R. Corazza Medicina Interna e Gastroenterologia, Universita` di Pavia, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy

Relationship between spirituality and cancer disease: ‘‘SOSSpiritual Oncological Survey’’ questionnaire as evaluation tool for the clinical practice G. Cristina, M.A. Ricciotti, R. Gareri, E. Capomolla, V. Felicetti, L. Cifaldi U.O.C. Oncologia Medica, Azienda USL RM G, Ospedale Parodi Delfino Colleferro, Rome, Italy Introduction: Cancer disease is a strong event that somehow changes human experience affecting physical, psychological and spiritual dimensions. Spirituality is what gives ultimate meaning and purpose in an individual’s life and modifies the perceived quality of health status. This is especially true for chronic and degenerative diseases. Clinicians find it difficult to initiate a discussion about spirituality with the patients since they believe it is not in their role. On the other hand patients express little about their spiritual needs. Moreover spirituality is an aspect difficult to measure. Although only few Italian studies are available, literature evidence about a relationship between spirituality and medicine is increasing. Aim: In order to detect and meet spiritual needs in a clinical setting of cancer patients (CPs) the ‘‘SOS-Spiritual Oncological Survey’’ questionnaire was developed. Patients and Methods: Since 1st April 2011 SOS questionnaire was administered to 40 CPs receiving chemotherapy at our Medical Oncology Unit Day Hospital. The topics covered by the questionnaire were: spirituality, cancer disease, community relationship, coping with the disease and the role of health care in relation to this issue. SOS was divided into 10 items, one of which is qualitative-descriptive while the other nine are quantitative and coded according to a 4-point score: 1=not at all; 2=a little; 3=considerably; 4=very much. CPs showing evidence of psychiatric disease or cognitive impairment were excluded. Results: Forty CPs filled in SOS showing interest for the test (24 males, 16 females; age 66±10.4 years; 12 lung, 12 genito-urinary, 9 gastro-intestinal, 5 breast, 1 head and neck, 1 GIST cancer; 5 adjuvant setting, 35 metastatic setting; 2 not believer, 35 Catholics, 3

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Background: In the decade 2000 – 2009 we observed 170 consecutive patients with newly diagnosed pancreatic cancer. Their severe presentation, the poor survival rate and the diffuse comorbidity led us to to investigate the clinical factors which actually affect their prognosis. Patients and Methods: The main clinical characteristics at diagnosis were the following: males 100, females 70, mean age 65.8 years (SD: ± 10.2; range: 36.4 – 91.5); the staging was performed with spiral CT and 6 patients presented stage I (3.5%), 37 stage II (21.7%), 28 stage III (16.5%) and 99 stage IV (58.2%). The tumor arose in the pancreatic head in 91 cases, in the body in 17, in the tail in 20 and showed diffuse presentation in 42. One hundred and one patients were considered inoperable because of advanced disease and/or heavy anesthesiologic risk (due to severe comorbidity or advanced age); 19 patients received only palliative surgery and 50 were operated with radical intent. Chemotherapy, based on gemcitabine-containing regimens, was administered in 138 patients, and was combined with radiotherapy in 20. Histologic types (evaluated from surgical specimens or ultrasonography-guided needle biopsies) were ductal adenocarcinoma in 143 patients, intraductal papillary mucinous carcinoma in 5, acinar carcinoma in 4, adenosquamous carcinoma in 3, Signet-ring-cell carcinoma in 2, undifferentiated carcinoma in 4. Histology was not determined in 9 cases. Median survival was 9 months (range: 1 – 105) and presently 4 patients are alive, with evidence of disease. Survival was analysed by means of the Kaplan and Meyer’s technique, the differences were tested with the logrank method, and prognostic factors were investigated in relation to survival through multiple regressions applied to the proportional-hazards model. Results: A large number of factors derived from clinical presentation, histology and treatment were multivariately analysed: those retaining a statistically significant correlation with survival after the backward selection procedures were the following, in decreasing order of importance: administration of chemotherapy, time elapsed from the onset of signs and symptoms to the diagnosis, clinical stage, age, and surgical resection of the tumor. The surprising role of the time to diagnosis was further investigated in relation to the onset of the three most common signs and symptoms, i.e. jaundice, weight loss and

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 abdominal pain. By evaluating patients presenting only one of these symptoms we observed that the 30 subjects suffering weight loss had a median time to diagnosis of 11.5 weeks (range: 4 – 26), the 38 with abdominal pain were diagnosed after a median time of 4.3 weeks (range: 0.8 – 11.7), while those 19 complaining of jaundice alone received the correct diagnosis in a median of 2.1 weeks (range: 0.48.5). The 83 patients with more than one symptom had time to diagnosis of 14,6 ± 11.2 weeks. Indeed, the survival curves of these groups of patients differ with high level of statistical significance. Moreover, they did not differ in terms of relative survival (as expected form the data from the ISTAT, Istituto Nazionale di Statistica), thus excluding competing risks due to different comorbidity among groups. There is a trend towards a higher prevalence of advanced stages in patients presenting weight loss alone compared with those with either jaundice or abdominal pain, but statistically significant levels were not reached. We did not find any relationship between type or duration of symptoms and site of origin of the tumor within the pancreas. Conclusion: The severe prognosis of pancreatic carcinoma seems also to depend, to a limited but distinct extent, on the time between the onset of symptoms and diagnosis. Weight loss is related to a longer diagnostic delay, likely due to its subtle onset and late realization by the patient. Early diagnosis might be related to a lower prevalence of advanced stages, as simply suggested – but not demonstrated; other biological or clinical factors are likely involved.

A pivotal role for neck ultrasonography in the follow-up management of clinically selected very low-risk papillary thyroid microcarcinoma patients L. Lamartina, T. Montesano, F. Trulli, S. Lupo, M. Ammendola, A. Paciaroni, F. Cava, G. Ronga, S. Filetti, C. Durante Dipartimento di Medicina Interna e Specialita` Mediche, Universita` di Roma ‘‘Sapienza’’, Roma, Italy Context: Most papillary thyroid microcarcinomas (PTMCs, \ 1 cm diameter) are indolent low-risk tumors, but around 25% exhibit more aggressive phenotypes. Controversies have thus arisen over the optimum postoperative surveillance of PTMC patients. Objectives: We tested the hypothesis that clinical criteria could be used to identify PTMC patients with very low mortality/recurrence risks and sought to define the best strategy for their management and long-term surveillance. Design: We retrospectively analyzed data from 312 consecutively diagnosed PTMC patients with T1N0M0 stage disease, no family history of thyroid cancer, no history of head-neck irradiation, unifocal PTMC, no extracapsular involvement, and classic papillary histotypes. Additional inclusion criteria were complete follow-up data from surgical diagnosis to death or, in the absence of death, for at least 5 years after surgical diagnosis. All 312 had undergone (near) total thyroidectomy (with radioiodine remnant ablation in 137, 44% RAI group), and were followed yearly with cervical ultrasonography and serum thyroglobulin, thyroglobulin antibody and TSH assays. Results: During follow-up (5-23 years, median 6.7 years) there were no deaths or reoperations. The first (6-12 months after surgery) and last postoperative cervical sonograms were negative in all cases. Final serum thyroglobulin levels were undetectable (\ 1 ng/mL) in all RAI patients and 163 (93%) of non-RAI patients. Thyroglobulin levels showed no correlation with TSH levels in either subgroup. Conclusion: Clinical criteria can reliably identify PTMC patients likely to experience complete cures with total or neartotal thyroidectomy. In these cases (approximately 75% of all PTMC cases), postoperative RAI and TSH suppression are unnecessary: even without these measures, serum thyroglobulin levels generally become undetectable within 5 years of thyroidectomy. Cervical

S379 ultrasonography is the mainstay of follow-up: negative findings at the first postoperative examination are highly predictive of positive outcomes, so yearly examinations are probably not essential, particularly after the fifth year. Collectively, these findings indicate that accurate risk stratification can allow safe follow-up of most PTMC patients with a less intensive, more cost-effective protocol.

Association between malignant disease and a young age: the role of thyroid ultrasound in the surgical work-up S. Longo, P.P. Papappicco, V. Manfredi, M. Catacchio, E. Renna, A. Pezzolla, S. Antonaci Dipartimento di clinica medica, Immunologia e malattie infettive clinica medica II ‘‘C. FRUGONI’’ Policlinico Bari, Italy In thyroid nodular disease, an age of less than 25 years is associated with malignancy. We assessed this association in our clinical experience, as well as the role of US in surgical work-up. A retrospective analysis was made of 255 patients aged between 13 and 84 years, operated for thyroidectomy at the General Surgery Operative Unit ‘‘V. Bonomo’’ of Bari University Hospital between January 2008 and May 2010. A prior thyroid US-guided needle-biopsy was performed at the Outpatients Medical Clinic ‘‘C. Frugoni’’ of the same hospital. In patients who underwent total thyroidectomy (229), histology demonstrated a benign lesion in 127 patients and malignancy in 92 patients. Among those who underwent hemithyroidectomy (26), there were 20 benign and 6 malignant lesions. Total thyroidectomy was then performed in the latter patients, in accordance with the guidelines. Among the 13 patients aged under 25 years, 12 underwent total thyroidectomy, and in 10 cases the final diagnosis was carcinoma (9 papillary and 1 follicular). Hemithyroidectomy was performed for benign disease, confirmed by histology. The percentage of malignancy was 38% in patients aged over 25 years, versus 77% in patients under 25, confirming the association between malignant disease and a young age. Thyroid US and US-guided needle biopsy played a fundamental role in the surgical workup: in 77% of the cases of hemithyroidectomy histology confirmed that the lesion was benign.

Metabolic risk of colorectal cancer F. Mariani, S. Bursi, E. Mora, M. Stefani, P. Sena, P. Benatti, M. Ponz de Leon, L. Roncucci Universita` di Modena e Reggio Emilia; Dipartimento di Medicina e Specialita` Mediche, Policlinico di Modena, Italy Introduction: Colorectal cancer (CRC) is the result of interactions between environmental and genetic factors. Among the former, fat diets rich in animal fat and poor in vegetable, and the presence of chronic inflammatory bowel diseases are considered predisposing. The relationship between chronic inflammation and risk of cancer is strongly supported by several observations on cancer in many tissues and organs. Although inflammation is essential for host defense and tissue repair processes, when unregulated or excessive, it can contribute to ongoing tissue injury. As far as environmental factors associated with lifestyle are concerned, an excess weight, resulting in accumulation of body fat, may be a risk factor for the development of many diseases, such as coronary heart diseases and hypertension, but also some types of cancer. Several epidemiological studies have confirmed that an increase in Body Mass Index (BMI) is related to an increased risk of colorectal cancer. Several

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S380 studies have shown that obesity can be considered a disease with a low-grade of inflammation. However, the molecular mechanisms that link inflammatory changes to the development and maintenance of obesity remain poorly understood. Myeloperoxidase (MPO) is one of the main enzymes characterizing polymorphonuclear cell activation, and may link the inflammatory response to metabolic alteration and neoplastic transformation. Aim: This study aimed at evaluating whether some anthropometric and clinical parameters in patients who underwent colonoscopy were related to the presence of colorectal tumors, and whether this relation may be explained by the level of inflammation of normal colorectal mucosa, assessed through the count of MPO-positive cells. Methods: We collected 210 samples of normal colorectal mucosa from 90 patients during colonoscopy, and fixed in formalin and embedded in paraffin for histology. 34 patients had colonic or rectal carcinoma, or one or more colorectal adenomas, 56 subjects had normal colonoscopy and were used as controls. •

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For each patient, we measured the following clinical and anthropometric parameters: waist circumference, body mass index, blood pressure, and fasting glycemia, and correlated them to presence or absence of colorectal tumors at colonoscopy. For each samples, we evaluated immunohistochemical expression of myeloperoxidase in biopsies of normal colorectal mucosa, counting MPO-positive cell at 9100 magnification and correlated them to the above mentioned parameters of patients.

Results: Patients with waist circumference and BMI above or equal of the threshold (for waist: 102 cm for men and 88 cm for women, for BMI 25) had higher percentages of colorectal tumors than subjects with parameters below the threshold (45% vs 33% for waist, and 42% vs 33% for BMI). Similar increases in percentages of lesions was observed according to blood pressure (41% above 140/90 and 35% below 140/90) and even more evident according to fasting glicemia (64% above or equal to 110 mg/dl and 36% below). The mean number of MPO-positive cells in colorectal mucosa was strongly related to waist circumference, especially in women (2.9 ± 0.3 for waist equal or above 88 cm vs 1.6 ± 0.2 for waist below 88 cm, P\0.001). Similar results were obtained for BMI in women (3.2 ± 0.3 for BMI equal or above 25 vs 1.7 ± 0.2 for BMI below 25, P\0.001). No significant difference was observed according to blood pressure and fasting glicemia. Conclusion: Some anthropometric and clinical parameters are related to colorectal tumor risk and to the degree of mucosal inflammation as assessed by the number of MPO-positive cells. Thus, these easily measurable parameters may be useful in the identification of patients at high colorectal cancer risk.

Qualitative and quantitative assessment of cancer anorexia via a specific scoring system A. Molfino, L.M. Donini*, A. Arezzo di Trifiletti, M. Muscaritoli, A. Laviano, F. Rossi Fanelli Dept. Clinical Medicine, *Dept. Medical Physiopathology; Sapienza University, Rome, Italy Background: anorexia is a negative predicting factor in cancer patients. A qualitative and quantitative diagnostic tool is not available yet. Recently, ESPEN proposed an anorexia score based on a 12-item questionnaire with multiple questions anchored to a score (Clin Nutr 2010; 29:154-9). By experts’ consensus, a score B24 allows the diagnosis of anorexia. We aimed at comparing, in unselected cancer patients, the ESPEN anorexia score against more frequently used tools to diagnose anorexia.

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Methods: unselected cancer patients were considered for the study. The ESPEN anorexia score, a symptom-based questionnaire (i.e., early satiety, nausea/vomiting, changes in taste/smell, meat aversion; the presence of any of these symptoms allows diagnosis of anorexia), and a visual analogue scale (VAS; 0 mm=satiety, 100 mm=hunger) were submitted to patients, who were also requested to report recent changes of their appetite and to estimate their food intake. Data were statistically analyzed using Student’s t-test and are presented as M±SD. Results: 213 cancer patients (122 M:91F; 63.4±12.8 yrs) with tumors of different origins (69 lung; 32 breast; 17 pancreas; 16 gynecological; 15 colon-rectum; 11 head & neck; 11 kidney & bladder; 9 prostate; 7 stomach; 7 liver; 4 lymphoma, 4 myeloma; 4 sarcoma; 2 esophagus; 2 unknown origin; 1 leukemia; 1 mesothelioma; 1 astrocitoma) and at different stages were enrolled. Anorexia score is related to VAS (r=0.34). Subjective reduction of appetite was reported by 37% of the patients (n=80), 47% reported no change (n=100), and 16% reported improved appetite (n=33). Anorexia score of self reporting anorexic patients was significantly lower than in patients with stable and improved appetite (25.2±7.3 vs 35.3±7.3 vs 33.0±7.6, respectively; p\0.01). The anorexia score of patients reporting food intake B50% of usual (31% of the population, n=66) was significantly lower than patients without changes in food intake (23.1±6.5 vs 34.8±7.0, respectively; p\0.01). According to the anorexia score, 54 patients were anorexic (25% of the population), whose VAS was significantly lower than non anorexic (4.5±2.2 vs 5.9±2.5, respectively; p\0.01). The symptom-based questionnaire identified 146 patients as anorexic (68% of the population), whose VAS was significantly lower than non anorexic (5.0±2.3 vs 6.8±2.5, respectively; p\0.01). Conclusions: similarly to symptom-based tools, anorexia score reliably identifies cancer patients with reduced appetite. The difference in the prevalence of anorexia when using the score or the questionnaire suggests that the proposed threshold of B24 is too strict.

A paraneoplastic syndrome confused for a primary psychiatric disorder S. Pugliese, L. Castorani, A. Mele, C. Capobianco, G. Palasciano Clinica Medica I ‘‘A. Murri’’ Azienda Ospedaliera Universitaria Policlinico di Bari, Bari, Italy B.A. male, 42 years old, tabagist of 30 cigarettes/day, gas station attendant, with history of schizoaffective disorder in therapy with neuroleptics drugs, came to our attention from the emergency department with diagnosis of ‘‘hyponatremia in patient with schizoaffective disorder’’. The patient, in his clinical history had only two accesses in hospital. The first time, he was hospitalized in a psychiatry division because of neuropsychiatric symptoms and dismissed with diagnosis of ‘‘hyponatremia due to excess of water introit in schizoaffective disorder’’. The second time he was hospitalized in an internal medicine division and dismissed with diagnosis of ‘‘hyponatremia probably due to antipsychiatric drugs in patient with schizoaffective disorder’’. He was admitted to our division 5 months after the recover in psychiatry, and because the presence of hyponatremia with low blood osmolality, we studied the renal function of 24 hours that informed us about a condition of hypernatriuresis and high urinary osmolality. The patient showed anterograde amnesia. Because of the presence of two great risk factors like tabagism and cronic inhalation of polycyclic aromatic hydrocarbons we thought the possibility of a paraneoplastic syndrome of inappropriate secretion of ADH (SIADH). We prescribed a CT of thorax that evidenced a stenosis of the upper branch of the main left bronchus. The patients underwent bronchoscopy that

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confirmed the bronchus stenosis, but the histological exam was negative for neoplasm. The thoracic surgeon decided to repeat the exam, but again the histological exam was negative for neoplasm and oriented to a inflammatory process. Because our conviction that there was a paraneoplastic syndrome, because the young age of the patient, together with the surgeon, we decided to make a thoracotomy. The histological report was: ‘‘small cell carcinoma of the lung highly undifferentiated’’. The patient after a chemotherapic cycle had complicances and an acute respiratory failure that brought to death. There are three important aspects in this clinical case:

HCC detection at early stages as well as by the development of new multimodal therapeutic strategies that increases the number of patients susceptible to curative treatment. According to the HEPATOCATT group experience, a multimodal individualized treatment seems to be the only available tool to delay the indication to antiangiogenetics in HCC management. Patients that cannot benefit from a surgical or locoregional treatment are more rapidly considered for antiangiogenetics. The multidisciplinary evaluation of HCC patients and our system of sharing informations and strategies seems to be the better therapeutic approach to this complex disease.

1. This is a situation in which neurological symptoms due to a clinical condition like hyponatremia have been confused like a primary psychiatric disorder. 2. During the first admission in an internal medicine division, was ignored the possibility that the psychiatric diagnosis was wrong and the patient was treated only with saline solutions without making a simple exam like the study of the renal function of 24 hours which instead open us the road to the diagnosis. 3. Probably the late in diagnosis should be avoided if the patient was studied with a more ‘‘internistic’’ point of view.

Pneumology

A multimodal individualized treatment is able to delay the indication to antiangiogenetics in patients with hepatocellular carcinoma. The HEPATOCATT group experience

Introduction: Patients with obstructive sleep apnea syndrome (OSAS) who have concomitant chronic obstructive pulmonary disease (COPD) are more prone to develop severe respiratory failure and probable death than patients with OSAS alone. However there are sparse reports that in some patients with OSAS induced acute respiratory failure, the severity of abnormal pulmonary function is less than what would be expected to cause the respiratory failure. Here we present a case of a patient with unknown severe OSAS who developed acute respiratory failure in course of upper airway tract infection. Case report: A 69-years old man (BMI 29 kg/m2) presented protracted loss of consciousness preceded by confusion, limb movement, jaw trismus while he was watching TV at home late in the afternoon. Since 4-5 days he was experiencing upper airway tract infection with significant rhinorrhea. His past medical history was unremarkable but for thalassemic trait and a previous gout attack. Upon arrival, the Emergency Staff (118) found: GCS 5, arterial pressure 110/70 mmHg, heart rate 107/min, oxygen saturation 90% while breathing room air. After sedation, orotracheal intubation was performed and pure oxygen was administered, while starting dopamine infusion. During transport to the hospital oxygen desaturation was evident despite continuous oxygen administration. Arterial blood gas analysis performed in the Emergency Room showed: pH 7.20; pCO2 55 mmHg; pO2 41 mmHg; lactic acid 4.3 mmol/L; HCO3 22 mmol/L. The only relevant findings within laboratory tests were: white blood cell count was 18.33x109/L with 83.5% neutrophils, C-reactive protein 1.05 mg/dl (\0.5). The chest X-ray showed atelectasis of the left lung caused by selective intubation of the right main bronchus; a correct repositioning after bronchoscopy followed. A chest CT excluded acute pulmonary thromboembolism, and head CT excluded acute cerebrovascular accident. The ECG and the echocardiogram were unremarkable. The patient was initially kept sedated and admitted to the Intensive Care Unit. There, a rapid recovery of the state of consciousness occurred after discontinuation of sedation and the patient was then transferred to the Geriatric Department. Here a newly performed head CT to exclude ischemic or hemorrhagic lesions, showed inflammatory tissue in the left maxillary sinus and ethmoidal cells; among laboratory examination, white blood cell count was 12.56x109/L with 75.8% neutrophils and C-reactive protein was 7.14 mg/

E. Rinninella, F.R. Ponziani, M. Zocco, V. Cesario, M. Novi, M. Garcovich, M. Pompili, L. Riccardi, A. Grieco, L. Miele, N. DE Matthaeis, M. Biolato, B.E. Annicchiarico, M. Siciliano, G.L. Rapaccini, G. Gasbarrini, A. Gasbarrini Internal Medicine and Gastroenterology, Italy Introduction: HEPATOCATT study group is a multidisciplinary team working from 2008 in Gemelli Hospital in Rome on HCC management. Patients are weekly evaluated and considered for all the available treatments, surgical, locoregional or even the innovative antiangiogenetic drugs. Aim and Methods: To evaluate improving efficacy and quality of a multidisciplinary team, investigating the frequency and the time from the first evaluation to antiangiogenetic drugs indication. Results: From May 2008 to May 2011 we enrolled 455 patients with primitive lesions of the liver. HCC was diagnosed according to AASLD guidelines in 380 (83,5%) patients. Considering the entire observation period, 84 out of 380 patients (22%) (66 male and 18 female) received indication to first line antiangiogenetic drug (sorafenib, sunitinib, brivanib), after exclusion of other curative strategies. When we stratified patients according to the year of enrollment: 22 out of 105 (21%) HCC patients received indication to antiangiogenetic drugs in the first year, 41 out of 207 (20%) patients in the second year and 21 out of 143 (14,6%) patients in the third year. On the whole, 46 out of 84 patients (54.8%) received a multimodal treatment before the indication to antianigiogenetics. Interestingly, the mean time before the indication to antiangiogenetics progressively increased during the years: 4.64±11.85 months in the first, 8.94±12.95 months in the second, 13.25±15.05 months in the last year. An effective multimodal ‘‘pre-antiangiogenetic’’ treatment was the only factor capable to delay the indication to antiangiogenetic drugs (p\0.0001; OR 0.306; 95% CI:11.360, 32.984), which, in turn, were reserved to patients whose performance status did not allow a surgical or locoregional treatment (p=0.018; OR 0.761; 95% CI: 1.485, 14.178). Conclusion: The number of patients candidated to antiangiogenetic drugs was lower in the last year than in the previous two years. This could be explained by a better follow up programme that allows the

Acute respiratory failure in a patient with upper airway infection and unknown obstructive sleep apnea syndrome S. Caravita*, L. Carassale**, S. Caporotundo**, A. Foresi***, S.C. Wu*, M.B. Secchi* *U.O.C. Medicina Interna, **U.O.C. Geriatria, Ospedale Bassini; ***U.O. Pneumologia, Ospedale Sesto San Giovanni, Azienda Ospedaliera Istituti Clinici di Perfezionamento, Milano, Italy

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dl. A course of antibiotic therapy with ceftriaxone and azithromycin was started; ramipril 10 mg, amlodipine 10 mg and acetyl salicylic acid 100 mg per day were introduced for the detection of high blood pressure. In search of a cause for the severe acute episode occurred, many diagnostic examinations were performed: extensive laboratory tests, serial ECG, 24-hours ECG recording, ECG stress test, echocardiogram, chest X-ray, carotid Doppler ultrasound, electroencephalogram, abdomen CT, head MRI, neurologic and cardiologic examinations, spirometry. All the aforementioned investigations were unremarkable, while polysomnography revealed a severe OSAS (AHI 57.4/hour) even if for technical problem oxygen saturimetry could not be available. The patient was discharged in good health with advice of starting nocturnal CPAP treatment and with persistent well-being at follow-up. Conclusions: We agree with the Authors who support the opinion that acute respiratory failure can occur in OSAS patients even without COPD or significant obesity, as in the case presented. We think that the upper airway tract infection (rhino-sinusitis with profuse rhinorrhea) in our patients was a possible trigger of the acute event in an unknown severe OSAS.

Comparison of culture positive and culture negative HCAP and CAP M. Carrabba, M. Zarantonello, C. Hu, G. Fabio Dip. di Medicina Interna, UO Med. Int. 1-A, Universita` degli Studi di Milano & Fondaz. IRCCS ‘‘Ca’ Granda’’ Ospedale Maggiore Policlinico, Italy Objective: The aim of this study is to describe the severity of illness and 30-day mortality among culture-negative (CN) and culturepositive (CP) patients with health-care-associated pneumonia (HCAP) and with community-acquired pneumonia (CAP). Methods: We used a prospective cohort study, examining adult patients with HCAP and CAP admitted to Internal Medicine Dept. in a tertiary care urban teaching hospital. Microbiologic studies were performed within 36 hours of admission: sample of blood cultures, of sputum, of bronco-aspirate, of bronchoalveolar-lavage, urinary antigen and serum antibody detection. Results: Six hundred twenty-nine patients with pneumonia were identified over a 6-year period of whom 141 (22.4%) were CP. Among the non-CP patients, 110 (17.5%) had no respiratory cultures obtained, and 378 (60.1%) had no growth or non-pathogenic oral flora identified and were classified as CN. Severity of illness as assessed by PSI scoring system was lower in CN compared with CP patients in both HCAP (81.3%) and CAP (18.7%; p =0.010). The in-hospital mortality was lower for CN patients (CN 10.3% vs CP 16.3% vs CN not-executed 23.6%, p =0.001) while hospital length of stay was higher in CP (CN 13.7±7.8 days vs CP 15.8±10.5 days vs CN not-executed 12.5±9.4 days, p =0.020). Comparison of in-hospital survival shows that HCAP CN patients without cultures obtained have a mortality trend worse than both CN and CP patients (CN not-execute vs CN p\0.001; CN not-execute vs CP p=0.003; CN vs CP p=0.387). Conclusions: In this analysis, patients with CN had lower severity of illness, hospital Mortality, and hospital length of stay compared with CP patients. HCAP patients CN and without culture obtained seem to differ from patients with HCAP with positive microbiologic cultures.

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Healthcare-associated pneumonia therapy: should we own follow the guidelines? M. Carrabba, M. Zarantonello, F. Minonzio, G. Fabio Dip. di Medicina Interna, UO Med. Int. 1-A, Universita` degli Studi di Milano & Fondazione IRCCS ‘‘Ca’ Granda’’, Italy Published guidelines for the treatment of healthcare-associated pneumonia (HCAP) recommend initial broad-spectrum antibiotics with appropriate de-escalation based on culture results. Guideline recommendations are based on data from intubated patients, in whom cultures are easily obtained. This study aims to investigate the in-hospital and 30-day mortality, long of hospital stay in both CAP and HCAP related to the empirical antibiotic therapy started at admission, before that microbiological data were available.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Patients and Methods: All patients admitted to a university hospital in Milan with a diagnosis of pneumonia from 2007 to 2010 were prospectical enrolled. CAP and HCAP were identified on the basis of the existing criteria. HAP and aspiration pneumonia were excluded. Antibiotics prescribed on admission during hospital stay, and on discharge were recorded. The initial prescription depended by the attending physician choice on the basis of clinical judgment. The Pneumonia Severity Index (PSI) was used for risk-adjustment. Results: A total of 275 patients, of whom 135 HCAP, were included in the analysis. Culture positive were 26.7% HCAP and 18.6% CAP. The majority of CAP was started with monotherapy (50%), while the most of HCAP with dual-therapy (43%). Triple-therapy was addressed for 20.7% of HCAP and 8.6% of CAP. Considering HCAP high-risk PSI class, 14.8% (n=4) of culture negative and 15.8% (n=3) of culture positive were treated with tripletherapy, while 51.9% (n=14) of culture negative, 31.6% (n=6) of culture positive and 83.3% (n=10) of not-obtained culture were treated with monotherapy. In CAP group none of the patients treated with triple-therapy died, and there are no differences for mortality between mono (8.6%) and dual-therapy (12.1%, p=0.406). In HCAP group 30-day mortality was 24.4%; dual-therapy seems to be associated with less mortality (8.6%) compared to both monotherapy (36.7%) and triple-therapy (35.7%; p=0.001). No differences were observed for length of stay in hospital. Conclusion: In this single-center study, most of the patients with HCAP started with an empirical dual therapy had a 30-day mortality similar to the one of CAP patients and lower than patients treated with triple therapy.

A severe case of respiratory failure in a subject with legionnaires’ disease G.A. Piccillo*, G. Mannino**, A. MO’***, E.G.M. Mondati****, P. Caponnetto****, R. Polosa****, G. Gasbarrini***** *Dept of Emergency Medicine, **Division of Infectious Diseases ***Intensive Care Unit of Cannizzaro Hospital, Catania; ****Dept of Internal Medicine, University of Catania; *****President of the Italian Association in Experimental Medicine, Italy Introduction: Legionellosis is a potentially fatal infectious disease caused by Legionella, a Gram negative, aerobic bacteria. Legionellosis takes two distinct forms: Legionnaires’ disease, also known as ‘‘Legion Fever’’, which is the more severe form of the infection and produces pneumonia and Pontiac fever that produces a mild respiratory illness without pneumonia resembling acute influenza. Among adult community acquired pneumonia, Legionella pneumophila has the potential to spread and be a fatal type of pneumonia. Legionella is consistently reported among the most commonly identified pathogens in community-and hospital-acquired pneumonia. About 20 different pathogenic species have been reported, with Legionella pneumophila accounting for more than 80% of human infections. Legionnaires’ disease can be acquired by the inhalation of contaminated aerosols or by microaspiration of contaminated water. Domestic aquatic reservoirs have been described as a source both in nosocomial and community-acquired infections. The clinical features of pneumonia caused by Legionella spp. are diverse. Early symptoms include fever, malaise, myalgia, anorexia, headache and slightly productive cough. During the course of illness, fever exceeding 40C, stupor, and respiratory and even multiorgan failure may develop. Elevation of creatinine kinase

S383 and diarrhoea have been reported as disease-specific symptoms for legionellosis. Current treatments of choice are quinolones and macrolides (tetracyclines for children above the age of 12). The incidence of community-acquired pneumonia caused by Legionella is probably underestimated as many species and serogroups are not properly detected by available tests. For this reason the patients with community-acquired legionellosis need admission to the hospital and the Intensive Care Unit more than the patients with pneumonia of other causes. Case report: A 62 year-old woman, smoker (61.25 pack/year), medical doctor operating in Emergency Department and affected with diabetes mellitus and hypertension in treatment on insulin, Ace inhibitors and Calcium antagonists, was admitted to our Emergency Department for a chilly sensation and general fatigue since 3 days. On admission, his temperature was 39.4 C, heart rate was 117 beats/ min, blood pressure was 115/72 mmHg and respiratory rate was 26 breathing/min. Physical examination revealed fine crackles and marked dullness of the right middle lobe. Laboratory testing was remarkable for leukocytosis (13.400/mmc) and elevated C-reactive protein (CRP, 392 mg/dl, normal \ 5).Glycaemia was very increased (580 mg/dl). Hepatic, pancreatic and renal parameters as well as urinalysis were normal. Capillary blood gas analysis confirmed moderate hypoxia and respiratory alkalosis due to hyperventilation (pO2 66 mmHg, pCO2 26 mmHg, pH 7.51, HCO3 21.1 mmol l-1). Chest radiograph and computed tomography revealed a distinct confluent infiltration of the right middle lobe including two small cavitations. Pleural effusions were absent. Bronchial obstruction or external compression could be excluded. During initial antibiotic therapy with intravenous piperacillin/tazobactam for 24 h, the clinical symptoms worsened markedly and the patient was intubated due to a severe episode of respiratory impairment and transferred to the Intensive Care Unit. Luckily, the patient ameliorated within 48 hours. One day later she was extubated. Legionella pneumophila serogroup 2 was isolated from a bronchoalveolar lavage specimen (BAL). Sputum and cultures for other bacteria (including mycobacteria), fungi and respiratory viruses were negative. All blood cultures remained negative. On the basis of these results, we made a definitive diagnosis of L. pneumophila pneumonia. Identification of L. pneumophila in BAL fluid prompted a change of antibiotic therapy to intravenous moxifloxacin. The patient recovered quickly and was switched to oral moxifloxacin for a total of 12 days. Glycaemia markedly improved as the patient recovered. Discussion: People of any age may suffer from Legionnaires’ disease, but the illness most often affects middle-age and older persons, particularly those who smoke cigarettes or have chronic lung disease. Immunocompromised patients are also at elevated risk. In the case reported here, a clinical presentation with high fever, markedly elevated CRP and the radiographic presentation of cavitating pneumonia in a diabetic patient was suggestive of classical pneumonia caused by Streptococcus pneumoniae. In fact, in Legionary’s disease defined as ‘‘atypical pneumonia’’, the clinical presentation is different and the chest radiographic findings are neither lobar nor consolidating. Threequarters of patients with L. pneumophila pneumonia present with an abnormal chest X-ray: patchy pneumonic infiltrates, predominantly of the lower lobes, but also circumscribed or even lobar consolidations are observed, while cavitations are rather uncommon. The presence of cavitations in legionellosis is probably more common in immunocompromised subjects than in immunocompetent patients. In our patient and dear colleague, we suspected and diagnosed Legionella, even if radiographic appearance suggests pneumococcal pneumonia. Although antigen assays and serology were negative, test of BAL fluid helped us to detect Legionella pneumophila and confirm our diagnosis.

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S384 A very insidious fever A. Schiavo, M. Renis Medicina Interna, P.O. Cava de’ Tirreni, A.O.U. ‘‘S.G.di D. e R. d’A.’’ Salerno, Italy Introduction: A symptom, often considered almost banal, such as fever, may hide many pitfalls. The authors describe a complex clinical case started with fever. Clinical case: G.V. male, 70 years old; anamnesis: diabetes mellitus type II (NIDDM), high blood pressure, Alzheimer’s disease, chronic cerebrovascular disease. The patient applies to Emergency Room (E.R.) complaining that he has been suffering with diarrhoea and vomit for a few days. In E.R.: body pressure (B.P.): 110/70 mmHg; heart rate (H.R.): 105/min arrhythmic; respiratory rate (R.R.): 18/min. The following tests are carried out: • •

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Electrocardiogram: ‘‘Arrhythmia: atrial fibrillation’’; Altered haematochemical tests: White blood cells (WBC): 17060 (N 88%, L 7%), Hb: 10.8 gr/dl, Glycaemia: 242 mg/dl; Creatinine: 2.3 mg/dl, Potassium (K): 1.8 mEq/lt, AST 247 U/lt, ALT 170 U/lt, LDH 1270 U/lt, CPK 1720 U/lt (anamnesis: no recent traumatisms). Chest X-ray: ‘‘Shaded parenchymal thickness in the right lower area’’. Acid/Base balance, with oxygen support at 4 lt/min: pH 7,58, pCO2: 46, pO2: 77, HCO3-: 43,1.

The patient is therefore admitted into the Internal Medicine Department, where cortisone and intensive antibiotic therapy (piperacillin/ tazobactam ? levofloxacine) is immediately established, together with additional charge of potassium (KCl) and magnesium-sulphate. Discussion: Body temperature, WBC and HR, already allow a SIRS (Systemic Inflammatory Response Syndrome). Diagnosis: The parenchymal thickening at X-rays allows to consider sepsis (SIRS ? presumed or confirmed infectious process) and the contemporary presence of renal failure, respiratory failure and the increase of transaminase, lead to think about a MODS (Multiple Organ Dysfunction Syndrome) diagnosis which, associated to Sepsis, reveals all the gravity of the Sepsis, suggesting, therefore to adopt an associated antibiotic therapy immediately, according to the guidelines. Hypokalemia picked out at the Acid–Base balance, that shows metabolic alkalosis, is a direct consequence of the prolonged vomit. Rhabdomyolysis and arrhythmia, also present in the first phases of the hospitalization, are a consequence of hypokalemia. The end of the case: The patient is therefore discharged after eleven days of hospitalization, with normalization of all parameters, with the following diagnosis: ‘‘Severe sepsis and MODS. Rhabdomyolysis and hypokalemia in metabolic alkalosis. NIDDM. High blood pressure. Alzheimer’s disease. Chronic cerebrovascular disease’’. Conclusions: Following carefully the guidelines, despite the presence of few records, it is possible to arrive rapidly to a diagnostic and prognostic framing, carrying out a quick suitable treatment, also in case of complex clinical cases.

Care for patients with chronic obstructive pulmonary disease (COPD) in primary health, Castilla and Leon (Spain) Sierra-Martı´nez, Leticia; Martı´nez-Fuerte, Ma Rosario Sacyl-Valladolid Este, Castilla y Leo´n, Spain

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Objective: To determine the prevalence of COPD patients in our area to provide primary healthcare to provide comprehensive and continuous care in response to physical, psychological and social, through the development of prevention, promotion and rehabilitation. Methods: Using computerized records in the history of our Health Center, based at the Department of Care for patients with COPD Portfolio Sacyl Services (Health Castilla and Leon, Spain), which met the inclusion criteria of major or equal 40 years of age who meet at least one of the following diagnostic criteria: 1 - Have been diagnosed with the following diagnostic criteria spirometry: FEV1/FVC below 70% and FEV1 below 80%. 2-That it is a history of smoking, cough, sputum and/or dyspnea and spirometry is appreciated as a reduction in the FEV1/FVC ratio below 70%. FEV1, peak expiratory volume in one second of a forced expiration (expressed in milliliters). FVC: Forced vital capacity (FVC) (expressed in milliliters). Results: 1-Target population,[ 40: 10087, 5394 women, 4693 men. 2-COPD in 192 men and 52 women. 3-Age distribution of patients with COPD: 90-100 -12 men and 4 women. 80-90 - 60 and 12 women. 70-80- 63 men and 9 women. 60-70- 28 men and 17 women. 50-60 - 22 men and 7 women. 40-50 - 7 men and 3 women. 4-The overall prevalence of 2.41%, the male 4.09% and 0.96% in women. Conclusions: There is a record low of patients included in the Service to people with COPD in our Health Centre with a total prevalence of 2.41%, much lower than that estimated in Castilla y Leon is 10.3%, as the men 4.09% and women 0.96% lower than those in the community who are 15% and 5.5% respectively. Improvement Plan: Make records for the diagnosis of dementia in the Computer History of our Health Center to allow us to determine the prevalence of people with COPD to develop a plan that includes prevention, promotion and rehabilitation from our consultation primary care.

Rheumatology To insist… It’s ‘‘Still’’ the case! A. Belfiore, N. Pinto, M. Frualdo, A. Lasorella, A. Mele, G. Palasciano Clinica medica ‘‘Augusto Murri’’ policlinico, Bari, Italy S.M., male, 23 years old, with several hospital admissions in the last four months for thoracic pain and fever. During the first hospitalization thoracic CT scan concluded for pulmonary embolism, pleuric and pericardic effusion, mediastinal limphoadenopathies and an inhomogeneus tissue in thymic region. Warfarin and steroids were introduced in therapy. When steroids were stopped the patient presented again all the clinical symptoms. Next radiological exams (CT and MR) confirmed the presence of a thymic lesion compatible with the diagnosis of Thymoma; this hypothesis was supported by the finding of sieric hypogammaglobulinemia. The patient was addressed to surgeons who decided to remove the suspected thymic tumor. The histological exam excluded the presence of a thymoma. Synovitis and relapsing fever indicated the possibility of Familiar Mediterranean Fever but since the clinical manifestations did not regress after therapy with colchicine this diagnostic hypothesis was ruled out. Diseases like LES, other connectivitis, infections,

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 neoplasms, and other causes of recurrent fever were excluded and diagnosis of Still’s Disease was made. Still’s disease is a ‘‘diagnosis of exclusion’’ supported in our patient by the presence of biohumoral markers like leucocytosis, hyperferritinemia, increased inflammatory markers and persistent clinical manifestations without steroid therapy. High doses of steroids were prescribed with quick remission of all clinical symptoms. Anticoagulants were suspended. After a month of therapy the patient was still asymptomatic with the drop of ferritinemia levels and flogosis markers. Conclusions: Still’s disease symptoms often simulate other pathologies (connectivitis, infections, neoplasms). Diagnosis needs a careful clinical approach. In this case radiological findings complicated our job shifting the attention towards a thymic disease.

Macrovascular and microvascular damage in the course of mixed connective tissue disease observation and description of some cases V. Bruzzese, C. Marrese Nuovo Regina Margherita Hospital CHU of Internal Medicine, Section of Rheumatology, Rome, Italy Mixed connective tissue disease (MCTD) is an autoimmune disease that is relatively rare and almost exclusively affects females. It usually appears in the second and third decade of life but can also be observed in other age groups. It is described for the first time by Sharp et al. (1) as a disease characterized by typical clinical signs of other connective tissue diseases (scleroderma, LES, polymyositis) associated with the presence of a high titer of anti-ribonucleoprotein antibodies (Anti-RNP) in serum. MCTD, in fact, has a polymorphous clinical expression and may present multiple onsets. The most common symptom of onset is Raynaud’s phenomenon, which is sometimes severe, as well as edema of the fingers, myalgia (in 50% of cases), polyarthritis, acrosclerosis, and skin rash. Over the past two years, three patients with MCTD have come to our attention. Since the presence of a generalized multiorgan vasculopathy has been reported in literature (2) in some cases of MCTD, we studied our patients even from a vascular point of view. Thanks to the ability to perform, in a short amount of time, a nail fold videocapillaroscopy (VCP) and a Doppler ultrasound examination of the epiaortic arteries in the department of Angiology, we have been able to observe the progression of macroscopic and microscopic vascular damage associated with this connective tissue disease. G.Q., 72-year-old female, myalgia and Raynaud’s phenomenon, hypersedimetry, high positive ANA test (1:2560) and Anti-RNP (326). The VCP showed dystrophic, branched ‘‘bushy’’ capillary formations, ectasia and apical microaneurysms. The Doppler ultrasound showed, at the beginning of the internal carotid artery, a fibrocalcific plaque with irregular margins and, at the left carotid bifurcation and ipsilateral internal carotid artery, some fibrolipid plaque which produced a hemodynamically significant stenosis (80% of the vascular lumen). M.M., 74-year-old female, Raynaud’s phenomenon for years followed by skin sclerosis confined to the hands, positive ANA test with homogeneous and nucleolar patterns (1:1280) and Anti-RNP ([ 100). The VCP showed irregular distribution of capillary loops, localized ectasia, tortuosity, arborescent kinks in the form of a ball. The Doppler ultrasound showed thickening of the vessel wall (IMT = 1.4 mm) with hypoechoic atherosclerotic apposition at the cost of the internal carotid artery (30% of the vascular lumen). E.C., 68-year-old female, arthralgia and Raynaud’s phenomenon, Anti-RNP ([ 100) and ANA test (1:1280). The VCP showed microhaemorrhages, hairpin loops and ‘‘top hat’’ ectasia of the loop in its

S385 entirety with venular branch tortuosity. The Doppler ultrasound confirmed the presence of patchy hyperechoic plaque in the right carotid bifurcation, intimal thickening on the left and bilateral tortuosity of the internal carotid artery. Conclusion: The characteristic alterations of the capillaroscopic framework and the increase of carotid IMT observed in our patients are consistent with the data in literature (2) which indicate, in the course of MCTD, the presence of an extensive vascular proliferation, resulting in a narrowing of the lumen even of large vessels such as aorta, coronary, pulmonary and renal arteries. We deduce that the frameworks described are certainly the result of a missed diagnosis that allowed for the emergence of the most disabling manifestations, and, although not yet noted in these patients, the IMT is predictive of coronary artery disease and of cardiovascular and cerebrovascular events. We also believe that the VCP and the Doppler ultrasound of the epiaortic arterial vessels should become routine tests in all forms of connective tissue diseases. References 1. Sharp GC, Irvin WE, Tan EM, Gould RG, Holman HR. Mixed connective tissue disease—an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA). Am J Med. 1972;52:148–59 2. Maddison PJ. Mixed connective tissue disease: overlap syndromes. Best Pract Res Clin Rheumatol. 2000;14(1):111–24

Carotid intima-media thickness and bone mineral density in female patients with systemic sclerosis R. Cimino, S. Giancotti, M. Conte, M.T. Polistena, C. Pintaudi, V. Nestico`, S. Mazzuca S.O.C. Internal Medicine, Az. Osp. ‘‘Pugliese-Ciaccio’’ Catanzaro, Italy The CCA-IMT is widely used as an early indicator of atherosclerotic process, and it has been demonstrated to have an inverse correlation with bone mass. The systemic inflammatory status, associated with atherosclerosis, can induce smooth muscle cells to produce osteoblasts-related proteins. Recent findings (Busti C. 2009) demonstrate how matrix metalloproteinases can both stimulate smooth muscle cell migration through the internal elastic lamina into the intima, and generate monomeric collagen for the development of atherosclerotic plaque The Aim is to analyze bone mineral density (BMD) parameters in female patients with SSc and to evaluate the relationship between BMD and Carotid intima-media thickness (IMT) as a marker of atherosclerosis severity. Methods. 114 female pts, all postmenopausal, with SSc (ACR SSc criteria fulfilled),mean age 56.42 ± 4.76 years, mean disease duration 9.69 ± 5.9 years, mean BMI 25.34 ± 3.4 kg/m2, were evaluated for their BMD, T-score on lumbar spine and femoral neck by dual x ray absorptiometry (DXA). According to the criteria defined by LeRoy (1988),72 pts had Diffuse SSc subtype (63.1%) and 42 pts Limited SSc subtype (36.9%).All the patients underwent bilateral carotid ultrasonography with a 7.5-MHz lineararray transducer, and a duplex scanner (ESAOTE), at approximately 1 cm proximal to the bulb. The results were compared to the same parameters obtained in control group of 50 healthy women comparable according to age, menopause duration, body mass index. Student’s t test, Pearson and Spearman’s test were used, as appropriate. Results: 19.2%(22 pts)of SSc pts had osteoporosis, while 49.1% (56 pts) had osteopenia. We found lower BMD in SSc pts, compared control group (0,865±0,82 D-SSc vs 0,978±0,12 L-SSc vs 1, 129±0,10 control group, p\0,02; T-score: -2,43±1,61 D-SSc vs -

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S386 1,72±1,62 L-SSc vs- 0,30±0,92 control group, p\0,01).The mean common carotid artery intima media thickness (mm) were: 0,92±0,36 D-SSc vs 0,74±0,22 L-SSc vs 0,63±0,32 control group, p\0,01. In five D-SSc pts (4.3%) we found a localized irregular intima media thickening of 1,5 mm and were defined as carotid artery plaque and were related lower T-score. Conclusion: Our findings revealed that osteopenic syndrome is significant and frequent complication of Systemic sclerosis and suggest that bone turnover and carotid intima-media thickness are related to a common pathogenetic mechanism responsible for the simultaneous and frequent presence of osteoporosis and arteriosclerosis in these subjects.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 control 240±33PU), p[0,05. Ach–induced vasodilation was negatively correlated with ANA-levels in pts with SSc r=-0,66,p\0,001);a weaker negative correlation was also seen for ANA and SNP-mediated vasodilation (r=-0,35,p\0,01). No correlation was demonstrated for the scores of capillaroscopic alterations and vasodilatatory responses. Conclusion: our study indicate that elevated ANA directly reflect impairment of microvascular function in SSc pts, and to our knowledge our study is the first to show a significant correlation of endothelial function and ANA levels.

The effect of a sequential therapy with prostanoids and bosentan in the treatment of digital ulcers in sclerosis systemic patients Significant correlation of endothelial function and ANA levels in systemic sclerosis R. Cimino, S. Giancotti, C. Pintaudi, M. Conte, A. Costantino, G. Clerico’, S. Mazzuca S.O. C. Internal Medicine, Az. Osp. Pugliese-Ciaccio, Catanzaro, Italy Background: Functional and structural alterations of the arterial wall are related to morbidity and mortality in cardiovascular disease. Systemic Sclerosis (SSc) is a chronic multisystem autoimmune disease with the characteristic pathophysiologic triad of vascular damage, autoimmunity and fibrosis. Scleroderma vascular pathology serves as a paradigm for both structural vascular changes and endothelial dysfunction. Microvascular abnormalities are a key feature in SSc and seem to play a pathogenic role. There is an evidence for endothelial cells activations and or apoptosis as an early event. Objectives: We investigated digital skin microvascular blood flow by laserDoppler and morphological microangiopathy by videocapillaroscopy in pts with Systemic Sclerosis, and we investigated the relationship between endothelial function and serological markers of inflammation and activation of immune system. Methods: we performed the study on 24 consecutive patients (22 W- 2 M) with SSc from January to December 2010. The patients were selected for study if they fulfilled the diagnosis of SSc according to the criteria of the American College of Rheumatology and diagnosis of Limited Skin Sclerosis as defined by LeRoy (1988). The patients had a mean age 51,2 years (range 13-84), and mean duration of disease 12,2 years ± 7,5 (range 1-24 years). As expected all pts suffer from Raynaud’s Phenomenon and nailfold videocapillaroscopy (NVC) was performed on all patients. During NVC examination three parameters were strictly defined: number of capillaries, microhemorrhage, maximum diameter of megacapillary. All capillaroscopic findings were transformed into semiquantitative rating scale to score these changes: Score 0: fewer capillaroscopic alterations, characterized by well preserved capillary architecture and density, Score 3: more capillaroscopic alterations characterized by severe capillary architecture disorganization with loss of capillary and large avascular areas. LaserDoppler flowmetry was performed on all pts at baseline and then again at 1-min intervals after iontophoresis, with acetylcholine (Achendothelial dependent) and sodium nitropresside (SNP-endothelial independent), to determine maximum perfusion responses. Both drugs were iontophoresed simultaneously. Levels of ERS, CRP, and antinuclear antibodies (ANA) were determined. Data were analyzed using t-test and Pearson correlation analysis and are given as mean ± SD. Age and sex matched healthy volunteers (n=20) were used as controls. Results: Ach- induced vasodilation was reduced in pts with SSc (SSc 190± 14 PU vs control 270 ± 13 PU), p\0,001; while vasodilation to SNP did not differ significantly between groups (SSC 199±26PU vs

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R. Cimino, S. Giancotti, C. Pintaudi, G. Muccari, V. Nestico`, M.T. Polistena, A. Costantino, S. Mazzuca S.O. C. Internal Medicine, AZ. OSP. Pugliese-Ciaccio, Catanzaro, Italy Background: Systemic Sclerosis (SSc) is a chronic multisystem autoimmune disease with a characteristic pathophysiologic triad of vascular damage, autoimmunity and fibrosis. Microangiopathy is the main histopathologic feature that is early detectable in the course of SSc and digital ulcers are a major complication which influences the personal and professional life of patient. DU is painful, heals slowly, is difficult to treat and often require hospital based treatment. To treat vascular complications of SSc, the best approach include drugs that promotes vasodilatation. Objectives: to assess the variation of digital ulcers number in SSc patients receiving a combined therapy with prostanoids and endothelin receptor antagonist. We compared data of initial patient registration (December 2009) and three follow-up visit included by December 2010 to explore associations of disease subset, antibody profile, organ involvement, season, time interval after onset of Raynaud’s phenomenon with development of DU and we describe potential risk factors for DU by comparing patients with and without active DU at time of entry. Patients and methods: At time of entry in December 2009 a total of 142 (122Women-20Men) unselected consecutive pts with SSc were included in our study. They had mean age 51.2 years (range 13-84), disease duration 12.2 years ± 7.5 (range 1-24). All met the preliminary American College oh Rheumatology classification criteria for SSc. And according skin cutaneous subsets: 16 pts (11.3%) with Early Sclerosis, 12 pts (8.4%) with intermediate cutaneous SSc, 72 pts (50.7%) with Limited cutaneous SSc, 42 pts (29.6%) with Diffuse cutaneous SSc. As expected all pts suffer from Raynaud’s Phenomenon and nailfold videocapillaroscopy (NVC) was performed on all patients, and skin sclerosis was measured with Rodnan Skin Score (mRSS). During NVC examination three parameters were strictly defined: number of capillaries, microhemorrhage, maximum diameter of megacapillary. All capillaroscopic findings were transformed into semiquantitative rating scale to score these changes: Score 0: fewer capillaroscopic alterations, characterized by well preserved capillary architecture and density, Score 3: more capillaroscopic alterations characterized by severe capillary architecture disorganization with loss of capillary and large avascular areas. DU occurs in about onethird of SSc pts. The patients with DU were treated with the dual endothelin receptor antagonist bosentan, which was administered for one month at an initial dose of 62,5 mg bid and afterwards uptitrated to 125 mg bid and a parenteral infusion therapy with iloprost once daily for a total of 5 days. Results: At the start in December 2009: 36 pts (25,3%) had active digital ulcers, 106 pts (74,7%) without digital ulcers. Comparing 106

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 pts without digital ulcers (group A) vs 36 pts with active digital ulcers (Group U) we revealed: systolic blood pressure 144.8±20.1 mmHg (A) vs 143.3±20.4 (U) pNS; Body mass index 25.2±3.3 (A) vs 23.4±2.6 (U) p\ 0,32; Disease duration 10.8±3.2 years (A) vs 8.6±2.7 (U) p\0,32; age 49.6 ± 6.5 (A) vs 53.8±4.9 years (U) p\0,32; male sex: 5 pts (A), 15 pts (U) p\0,01; SCL-70 8 pts (A) vs 28 pts (U) p\0,01; total cholesterol 190±30 (A) vs 213±28 mg/dl (U) \p0,32; LDL Cholesterol 130±30 (A) vs 129±31 (U) pNS; HDL cholesterol 43±15 (a) vs 39±14 (U) p 0,32; Rodnan Skin Score 9.6±2.5 (A) vs 22.3±5.3 (U) p\0,32. Comparing the 36 pts with DU, the nailfold capillaroscopic analysis revealed: 8 pts with capillaroscopic score \1 and mRSS 9.6; 28 pts with capillaroscopic score 2,12 and mRSS 22.8. In this group we registered 6 deaths (4 male sex). Our study showed a correlation between capillaroscopic damage and a higher degree of skin score, a higher prevalence of DU in pts with SSc who were male, and had diffuse cutaneous subset with anti-SCL-70 antibodies and cardiac and lung involvement. More Digital Ulcers were present from February to May (p 0,036). Univariate analysis reveal a higher prevalence of SCL-70, Diffuse SSc, Male gender, PAH, oesophagus involvement, lung fibrosis in patients with DU (p\0,0001).Digital ulcers healed in 26 patients within an observational period of 2,80 months (min 1, max 6 months).After the follow-ups at December 2010 only 10 patients (7,04%) had active digital ulcers and only Diffuse SSc, SCL-70 and lung fibrosis are significantly associated with DU. Conclusion The decreasing incidence of DU in follow-ups is ascribed to management of DU and we illustrated good long term outcomes through the utilization of combined treatment modalities to prevent amputation, to improve ischemic rest pain and to spread up the healing process of disease related ulcers.

Deterioration of the lung function and presence of teleangiectases in systemic sclerosis R. Cimino, S. Giancotti, C. Pintaudi, S. Riccio, A. Costantino, M.T. Polistena, S. Mazzuca S.O.C. Internal Medicine, Az. Osp. ‘‘Pugliese-Ciaccio’’, Catanzaro, Italy Recent studies suggest that teleangiectases are associated with a more aggressive pulmonary involvement and with a worse clinical outcome in SSc. Teleangiectases are vascular lesions composed of vasodilated post-capillary venules without evidence of neovascularization or inflammation. Although they are thought to occurred more commonly in pts with Limited SSc, they became more numerous overtime in both Limited and Diffuse subtype. The Aim: to investigate the association between the presence of teleangiectases and lung involvement in a cohort of SSc Patients. Methods: during 2010 a total of 88 SSc patients with teleangiectases were assessed. All clinical parameters were evaluated and the presence of teleangiectases was assessed in 11 different body areas. The teleangiectasia’s score for each body areas was calculated: zero if teleangiectases were absent, 1 point if were 1-9, 2 point if C 10 teleangiectases were present. A total teleangiectasia’s score was obtained by the sum of the score of the each individual body area (max score 22).Lung function were assessed by evaluating the forced vital capacity (FVC) and the ratio between DLCO/FVC. Association between total teleangiectasia’s score and lung function was investigated by Spearmen’s rank correlation coefficient and independent associations were investigated using multivariate linear regression analysis adjusted for age, gender, disease duration, smoking habitus, immunologic parameters and p value\0,5 was considered significant. Results: We found: stellate teleangiectases in 4%, matted teleangiectases in 34%, both type in 62%. Body median teleangiectasia’s score: face 1,6- arms 0,7- hands 0,4- thorax 0,6-abdomen 1,4-back

S387 1,2- legs 0,8- feet 0,7. Female gender (79,9%), Age 54,7±12,9 years, disease duration 14,3±12,2 years; Diffuse subset in 16(18,2%), Limited subset in 62(70,4%), intermediate subset in 22,4%); Total teleangiectasia score: 7,07±0,72; FVC: 99,2±25,7; DLCO/ FVC: 92,6±22,3; Digital Ulcers in 8 pts(9,7%); Digital Amputation in 6 pts(6,8%):Asymmetric peripheral pulse in 10 pts(11,8%), claudicatio in 18pts(20,5%);Infarction in 6pts(6,8%); Creatinin 0,69±12 mg%;ACA (47,7%); SCL-70(27,3%). In multivariate linear regression analysis: Total teleangiectasia score vs. DLCO/FVC: rho 0,42 p\0,005. Conclusion: in the SSc cohort, the presence of higher total teleangiectasia’s score was associated with a more important deterioration of the lung function and teleangiectases in SSc are clinical marker of pulmonary involvement.

Treatment response in interstitial lung disease in inflammatory myopathies M.G. Danieli, L. Pettinari, R. Moretti, M. Permon, L. Maringeli Medical and Surgical Science Department, Polytechnic University of Marche & Ospedali Riuniti, Ancona, Italy Objective: Idiopathic inflammatory myopathies comprises a heterogeneous group of acquired muscle diseases, characterised by inflammatory changes on muscle biopsy. Morbidity and mortality are greatly affected by the appearance of interstitial lung disease (ILD). We reviewed the incidence, the clinical features and treatment response of ILD in a series of patients with Polymyositis (PM) and Dermatomyositis (DM). Methods: We reviewed the clinical notes of 77 consecutive patients with myositis followed from 1985 in Clinical Medicine Section. Myositis was diagnosed according to the Bohan and Peter’s criteria. A standardised protocol collected the demographic, clinical and serological data. Deaths were registered and causes of death ascertained. Results: Our series included 25 subjects with PM, 33 with DM, 8 and 11 with cancer- or connective tissue disease (CTD)- associated myositis, respectively. ILD was documented in 20 patients (26%). All of them had a restrictive pattern (FVC or total lung capacity \80% of the predictive value for age and height) at the pulmonary function testing (PFT) with a reduced diffusing capacity for carbon monoxide (DLCO). Ground glass opacities and fibrosis accompanied by a loss of lung volume and traction bronchiectasies were documented at high-resolution CT scanning of the thorax in four and sixteen patients, respectively. In our experience, the presence or absence of an antisynthetase antibody does not seem to influence the long-term outcome. Initially 50% of patients responded to glucocorticoid therapy alone. Eleven patients were treated with cyclosporine A with a complete or partial remission in more than 75% of the cases, in particular when used the early stage of the disease. Despite treatment, ILD-related deaths occurred in 25% of the patients, a higher percentage than that documented as for the disease related deaths (17%). Conclusions: Despite major progress in treatment, ILD in the course of PM and DM remain a severe complication, significantly affecting the survival and the quality of life of the subjects.

Systemic lupus erythematosus (SLE) associated with antiphospholipid syndrome (APS) and Guillain-Barre´ Syndrome P. Ghiringhelli*, R. Cattaneo*, A. Diana*, M. Ossola**, D. Uccellini** Azienda ospedaliera dibusto arsizio, Dipartimento medico; *S.C. Medicina, **U.O. Neurologia, Italy

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S388 Introduction: The complexity of differential diagnosis in internal medicine makes it, in most cases, difficult. Case report: A 33 years old woman, diagnosed with SLE for 8 years, in remission for 4 years, in oral anticoagulation therapy for previous deep vein thrombosis (DVT) and concomitant detection of APS, was hospitalized for myalgic pain and widespread of progressive deterioration of strength in all 4 limbs with difficulty in standing. The reflexes were present, the sensitivity appeared preserved. The brain magnetic resonance image showed the presence of a non recent infarcted area in the right hemisphere. The electromyography (EMG) was not oriented towards myasthenia. Lumbar puncture revealed the presence of protein elevation in cerebrospinal fluid (140 mg per deciliter), and 14 per microliter of white blood cell, mainly lymphocytes. In the suspicion of a Neuro-LES steroid therapy was initiated at high doses. Myalgic pain disappeared but, on the other side weakness worsened with onset of severe dysphagia and inability to keep her head erect. EMG was repeated and oriented towards a Guillain–Barre syndrome. After four sessions of plasmapheresis, the patient had regained an acceptable swallowing and partial control of the trunk. After 3 months she walked on crutches. Conclusions: The association between SLE and Guillain-Barre´ syndrome is rare but is reported in the literature.

T regulatory lymphocytes expression in lupus nephritis K. Giannakakis*, A. Gigante**, A. Onetti Muda***, R. Cianci**, A. Amoroso**, D.P.E. Margiotta****, F. Pugliese**, A. Afeltra**** *Department of Radiology, Oncology and Pathology, Sapienza University of Rome; **Department of Clinical Medicine, Sapienza; ***Department of Pathologic Anatomy, University Campus BioMedico of Rome; ****Department of Clinical Medicine, Immunology and Rheumatology, University Campus Bio-Medico of Rome, Italy Background: Lymphocyte regulatory T cells (Tregs) play an important role in the maintenance of immune tolerance and in the pathogenesis of autoimmune diseases, such as SLE. Identification of the intracellular marker FoxP3 is important in the context of Tregs. Several studies describe a quantitative or functional deficiency of Tregs in SLE. However, the role of Tregs in the lupus nephritis (LN) is still unclear. There are no data demonstrating a quantitative difference or quality of Tregs in the kidney of lupus patients and healthy subjects and lacks the existence of a prognostic relevance of Tregs infiltration in LN. Aim of the study: The study aims to evaluate the expression of FoxP3 positive regulatory T lymphocytes in the inflammatory infiltrate of LN classes compared to that crescentic glomerulonephritis (CrGn), acute tubulointerstitial nephritis (ATN) and nephroangiosclerosis (NAS). Materials and Methods: 27 consecutive patients with histologically proven LN (class III: 3 patients, class IV: 17 patients, class V: 7 patients), 3 patients with ANCA CrGn, 6 patients with NTA, and 2 patients with NAS. Sections of paraffin kidney biopsies have been stained by immunohistochemistry with CD3 and FoxP3 antibody, performed separately on consecutive sections. The number of FoxP3 positive cells and CD3 positive was counted using digitalization of slides with Aperio scanner for unit area mm2 and FoxP3?/CD3?. Results: CD3? were more expressed in ATN (5713/mm2) and in the CrGn (5121/mm2) than LN-IV (3558/mm2), LN-III (2491/mm2), NAS (2379/mm2) and LN-V (2220/mm2). Instead we found significantly decreased of FoxP3?/CD3? ratio in patients with LN-IV (1,6) and, although less significantly, in patients with CrGn (3) than in course of NAS (3,9), ATN (4), and LN-V (4,5). Conclusion: The results presented herein, although preliminary, suggest an important role of Treg in the pathogenesis of autoimmune

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 disease, particularly during the most active phases of LN, as observed in LN-IV class.

Spirometric parameters that better correlated with increased systolic pulmonary arterial pressure in scleroderma patients M. Lucci, I. Paglione, A. Kafyeke, A. Gabrielli, P. Fraticelli Istituto di Medicina Interna, Malattie Respiratorie e Immunoallergiche. Sezione di Clinica Medica, Universita` Politecnica delle Marche, Ancona, Italy Background: pulmonary arterial hypertension (PAH) occurs in 8-12% of patients with systemic sclerosis (SSc) and is widely recognized as a major complication of both the limited and diffuse cutaneous subtypes of SSc. Subtle symptoms and physical findings of pulmonary involvement can be missed and consequently a patient may present with advanced signs of right-heart failure and an ominous prognosis. Timely identification of PAH has assumed great importance because early therapeutic intervention among these patients could be beneficial. Rightheart catheterization (RHC) remains the definitive test in the diagnosis of pulmonary hypertension. However it is impractical as a screening test; therefore various non-invasive tests (Doppler echocardiography and pulmonary function tests) have been proposed as useful screening tests for PAH in SSc patients. Objective: to evaluate pulmonary function tests that best correlate with increased systolic pulmonary arterial pressure (sPAP) on echocardiogram to target SSc patients who will require RHC or frequent screening because at risk of PAH. Methods: 135 scleroderma patients referred to the Department of Medical Clinic at the Marche Polytechnic University of Ancona were reviewed. SSc was classified as limited or diffuse cutaneous subtype according to the criteria described by LeRoy et al. All SSc patients underwent Doppler echocardiography, pulmonary function tests and HRCT as well as routine clinical assessments. Exclusion criteria were left heart dysfunction and diagnosis of mixed connective tissue disease or other connective tissue diseases. Results: 113 scleroderma patients were included in this retrospective analysis; 37 patients had autoantibodies against centromere (32,7%) and 46 were positive for Scl-70 antibodies (40,7%). Mean sPAP was 32,5±15,2 mmHg, with values [ 36 mmHg in 25 patients (28%). A significant correlation was observed between DLCO%, DLCO/VA%, FVC%/DLCO% (RATIO) and sPAP in the whole population and in anti-centromere positive subgroup, but not in the Scl-70 subpopulation. No correlation was found between FVC% and sPAP. Among 15 scleroderma patients who underwent RHC, hemodynamic data confirmed clinical suspicion of PAH in 9 of them. Conclusion: this retrospective study suggests that RATIO, DLCO/ VA% and DLCO% all correlate significatively with increased systolic pulmonary arterial pressure on echocardiogram in scleroderma patients. These non-invasive tests represent functional indexes able to identify, early in the course of SSc, patients with increased pulmonary arterial pressure. Patients presenting with anti-centromere antibodies, RATIO[ 2.0 and sPAP[ 36 mmHg by echocardiography, seems to be the most likely subgroup to develop PAH, requiring closer assessment.

Metabolic syndrome and vascular damage: a study of microcirculation using nailfold videocapillaroscopy A. Matarangolo, V.C. Rollo, F.P. Soldo, D’G. Alessandro Clinica Medica Azienda Ospedaliera Universitaria, Ospedali Riuniti Foggia. Centro Studio Malattie Apparato Osteoarticolare ed Immunoproliferative, Italy

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 Introduction: Patients affected by Metabolic Syndrome present a group of contemporaneous risk factors leading to alterations of macrocirculation and microcirculation. Several studies have analyzed the alterations of microcirculation in patients affected by essential hypertension, diabetes mellitus or dyslipidemia, but few studies in our knowledge exists which focalize on the alterations that microcirculation undergoes when these pathological conditions occur all together at the same time, like in Metabolic Syndrome. The aim of this study was to verify the structural and functional characteristics of the microcirculation in patients affected by Metabolic Syndrome using videocapillaroscopy. Patients and Methods: We enrolled 30 Caucasian patients affected by Metabolic Syndrome, 24 women and 6 men, with mean age about 56 years, using NCEP-ATPIII criteria for the diagnosis. We performed nailfold videocapillaroscopy by a videocapillaroscopic instrument type ‘‘VideoCap’’ with contact cold light probe. Results: Patients with Metabolic Syndrome showed a constant videocapillaroscopic pattern, characterized by contemporaneous presence of edema, tortuous capillaries, decreased bloody flow velocity and reduced capillary density, accompanied by other changes different from patient to patient. These alterations were recurrent, but also they presented an elevated damage score, sign of high severity of microangiopathy. Conclusions: In according to the images obtained, the constancy and the elevated score of the alterations found, makes us suppose that in Metabolic Syndrome exists a recurrent videocapillaroscopic pattern which is the representation of an extended endothelial damage. So videocapillaroscopy demonstrated to be a simple and valid instrument for the analysis ‘‘in vivo’’ of microcirculation and for follow-up of these patients.

S389 Results: 36 pts (25,3%) had digital ulcers, 106 pts (74,7%) without digital ulcers. Comparing 106 pts without digital ulcers (group A) vs 36 pts with digital ulcers (Group U) we revealed: systolic blood pressure 144.8±20.1 mmHg (A) vs 143.3±20.4 (U) pNS; Body mass index 25.2±3.3 (A) vs 23.4±2.6 (U) p\ 0,32; Disease duration 10.8±3.2 years (A) vs 8.6±2.7 (U) p\0,32; age 49.6 ± 6.5 (A) vs 53.8±4.9 years (U) p\0,32; male sex: 5 pts (A), 15 pts (U) p\0,01; SCL-70 8 pts (A) vs 28 pts (U) p\0,01; total cholesterol 190±30 (A) vs 213±28 mg/dl (U) \p0,32; LDL Cholesterol 130±30 (A) vs 129±31 (U) pNS; HDL cholesterol 43±15 (a) vs 39±14 (U) p 0,32; Rodnan Skin Score 9.6±2.5 (A) vs 22.3±5.3 (U) p\0,32. Comparing the 36 pts with DU, the nailfold capillaroscopic analysis revealed: 8 pts with capillaroscopic score \1 and mRSS 9.6; 28 pts with capillaroscopic score 2,12 and mRSS 22.8. In this group we registered 6 deaths (4 male sex). Our study showed a correlation between capillaroscopic damage and a higher degree of skin score, a higher prevalence of DU in pts with SSc who were male, and had diffuse cutaneous subset with anti-SCL-70 antibodies and cardiac and lung involvement. Conclusion: In pts with DU we revealed highest value of total cholesterol and a significantly lower HDL cholesterol. These results are of clinical relevance for counselling patients and for considering prophylactic strategies with statins for patients with secondary Raynaud’s Phenomenon who have not yet developed DU.

Pulmonary involvement in Sjogren’s syndrome R. Moretti, S. Gambini, L. Pettinari, L. Paolini, M.G. Danieli Medical and Surgical Science Department, Polytechnic University of Marche & Ospedali Riuniti, Ancona, Italy

Lipid profile and pro-thrombotic disorder in systemic sclerosis patients S. Mazzuca, S. Giancotti, C. Pintaudi, G. Muccari, V. Nestico`, M.T. Polistena, R. Cimino S.O. C. Internal Medicine, Az. Osp Pugliese, Ciaccio, Catanzaro, Italy Background: Systemic Sclerosis (SSc) is characterized by widespraid vascular lesion and endothelial dysfunction, fibrosis and immune abnormalities that might advance occlusive vascular complications. Objectives: to evaluate the lipid pattern in patients with SSc and to investigate the potential involvement of lipid abnormalities in onset and progression of digital ulcers. Patients and Methods: in 2010 a total of 142 (122Women-20Men) unselected, consecutive pts with SSc were included in our study. They had mean age 51.2 years (range 13-84), disease duration 12.2 years ± 7.5 (range 1-24). All met the preliminary American College oh Rheumatology classification criteria for SSc. And according skin cutaneous subsets: 16 pts (11.3%) with Early Sclerosis, 12 pts (8.4%) with intermediate cutaneous SSc, 72 pts (50.7%) with Limited cutaneous SSc, 42 pts (29.6%) with Diffuse cutaneous SSc. As expected all pts suffer from Raynaud’s Phenomenon and nailfold videocapillaroscopy (NVC) was performed on all patients, and skin sclerosis was measured with Rodnan Skin Score (mRSS). During NVC examination three parameters were strictly defined: number of capillaries, microhemorrhage, maximum diameter of megacapillary. All capillaroscopic findings were transformed into semiquantitative rating scale to score these changes: Score 0: fewer capillaroscopic alterations, characterized by well preserved capillary architecture and density, Score 3: more capillaroscopic alterations characterized by severe capillary architecture disorganization with loss of capillary and large avascular areas.

Objective: Sjo¨gren’s syndrome (SS) is a chronic and systemic autoimmune disease characterized by a wide variety of glandular and extraglandular manifestations. Pulmonary involvement is frequently reported and the most common features include xerotrachea, small airway obstruction, interstitial lung diseases (ILD), pulmonary hypertension and primary pulmonary lymphoma. Interstitial lung disease is reported in 8-38% of the cases ranging from alveolitis to reticulation and honeycombing of the lung parenchyma. We analyse the incidence and the clinical features of ILD in a large series of patients with SS. Methods: The medical notes of 100 consecutive subjects with SS followed by our Clinical Medicine Section from 1985 to 2011 were reviewed. Diagnosis was made according to the American-European criteria. Demographic, clinical and serological data were collected following a standardised protocol. Results: Fifteen patients with ILD, confirmed by the thoracic highresolution CT scan evaluation, were identified. Only seven patients (5%) had dyspnoea on exertion, the others were asymptomatic. Clinical examination showed crackles (rales) in all patients evaluated. Pulmonary function testing (PFT) documented a restrictive pattern of the disease (FVC or total lung capacity \80% of the predictive value for age and height) with a decrease in the diffusing capacity for carbon monoxide (DLCO) in all of the patients. High-resolution CT scanning of the thorax revealed micronodules, linear opacities, ground glass opacities and fibrosis. In three cases, intravenous cyclophosphamide was used in monthly infusions, methotrexate in one patient and glucocorticoids in the other cases. After a five years follow-up period, only five patients showed resolution of ground glass areas, documented by high-resolution CT scanning; only in two cases there was a disease progression, with reticular and nodular tomography aspect.

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S390 Conclusion: In our series, pulmonary involvement in SS is quite common, with an incidence of about 15%. The relatively high frequency of asymptomatic subjects, with subclinical interstitiopathy, documented by the presence of restrictive framework to functional tests and radiographic features, suggests the importance of early diagnosis.

Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 obtain with this treatment. Because of paucity of the RCTs, further studies need to confirm the effectiveness of spa therapy in FMS patients.

Interstitial lung disease in systemic lupus erythematosus L. Pettinari, R. Moretti, L. Marinangeli, G. Nicoletti, M.G. Danieli

A critical review of clinical researches on spa therapy in fibromyalgia L. Petraccia*, G. Mennuni*, M. Grassi*, A. Serio**, M. Fontana***, J. Campanella*, F. Libri*, C. Maxia*, S. Nocchi*, A. Fraioli* *UOC Medicina Interna E, Terapia Medica e Medicina Termale, Dip. Medicina Interna e Specialita` Mediche, Sapienza Universita` di Roma; **Universita` Campus Bio-Medico di Roma; ***Dip. di Scienze Biochimiche, Sapienza Universita` di Roma, Italy Background: Fibromyalgia is a chronic syndrome of unknown etiology; it is characterized by chronic widespread musculo-skeletal pain and morning stiffness, induced tenderness by digital pressure on muscle and tendon insertions (tender points), sleep disturbances, chronic fatigue, depressive episodies, anxiety. Irritable bowel, irritable bladder and temporo-mandibular syndromes are often associated. Therapy of fibromyalgia includes: non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, ansiolytics, corticosteroids, selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), MAO–inhibitors, tricyclic antidepressants, alfa-2-delta ligands pregabalin and gabapentin. Reuptake inhibitors of serotonin and norepinephrine, tricyclic antidepressants, alfa-2-delta ligands pregabalin and gabapentin showed a better efficacy. There are also non pharmacological therapies. Aim: In the present systematic review we want to evaluate the studies regarding the efficacy of spa therapy such as bath or mud-bath therapy in fibromyalgia. Methods: We collected the studies regarding Fibromyalgia Syndrome (FMS), searching in Pub Med, Medline, Cochrane Library, EMBASE, Web of Science by key words fibromyalgia, spa therapy, balneology, mud-pack therapy, mineral waters. In our study we chose only studies done using mineral waters as baths or, mixed with solid substances, muds; we excluded therapy based on the use of tap water (hydrotherapy) or sea water. Studies from 2000 to 2010 are collected. Results: We found 6 studies out of 64, 5 RCTs and 1 retrospective research; they have homogenous methods of collection of patients, all fulfilling ACR criteria for diagnosis, and homogenous tools for evaluation of clinical outcome. The main methods used for the clinical assessments were: FIQ (fibromyalgia impact questionnaire), VAS (visual analogue scale), TP (tender point count) and BDI (Beck depression inventory). Spa therapy (baths or baths and mud-packs) was applied in 143 patients and other 93 were included in the control group. In all the studies the end points were evaluated at start and at the end of therapy but other times were used in the single studies (three weeks, one, three, six or nine months after the end of therapy). All of them found significant improvement of symptoms measured by FIQ, VAS, TP and BDI at the single step of the follow-up. The results were controlled by statistical analysis using the main tests to evaluate the differences between the experimental and the control group. In one study improvement was evaluated only after the end of spa therapy and a significant decrease of blood levels IL-1 and LTB4 was observed. Conclusion: The researches on the efficacy of spa therapy in the treatment of FMS confirm the good result which is possible to

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Medical and Surgical Science Department, Polytechnic University of Marche & Ospedali Riuniti, Ancona, Italy Background: Interstitial lung disease (ILD) in systemic lupus erythematosus (SLE) is not as well-known as the cutaneous, rheumatological and renal manifestations. It can present acutely or chronically, with acute presentations. ILD can be the result of a disease’s direct lung involvement or the complication due to other conditions such as pulmonary thromboembolic disease or drug toxicity. Objectives: We report our data related to a series of patients affected by ILD associated with SLE followed by our Department. Methods: SLE was diagnosed according to the Tan revised criteria. Demographic, clinical, laboratory and therapeutical informations were collected through a standardized protocol. ILD was defined by the presence of a severe shortening of CO-diffusing capacity associated with a restrictive pattern by spirometry and a high resolution tomography showing reticulonodular infiltrates in accord with the diagnosis. Results: 87 consecutive patients (78 F and 9 M) with LES were included in our observation. The mean age of SLE onset was 33 years. Pulmonary fibrosis was present in 13 subjects (15%) with mean age of 38 years and mean disease duration of 11 years at the onset of the respiratory involvement. Six patients presented with dyspnoea while 7 were asymptomatic for respiratory symptoms. They all were treated with steroid associated to an immunosuppressant (Cyclophosphamide in 7 patients and Methotrexate in 6 patients), thus obtaining a substantial stability of the interstitial involvement at last follow-up. Conclusion: ILD represents a late complication in the course of SLE. As with other connective tissue diseases, early and specific therapeutic intervention is indicated to preserve pulmonary function slowing down the progression of the damage.

A case of anemia in a postmenopausal woman with osteoporosis and vertebral fracture treated with intermittent parathyroid hormone A. Ragno*, A. Silvestri*, D. Pierangeli*, L.S. Martin*, F. Angelini#, A.E. Catucci* *S.C. di Medicina Interna e Nefrologia; #S.C. di OncologiaEmatologia. Ospedale ‘‘Regina Apostolorum’’, Albano Laziale (RM), Italy It’s presented a case of a 63-year-old woman with severe postmenopausal osteoporosis (menopause at 51 years of age; lumbar BMD t-score was -2,5 SD, Total Femoral BMD t-score was -2.0 SD; her plain radiographs of the spine revealed three vertebral fracture at T12, T10, T9). The patient reported no family history of any disease, she reported history of hypertension and colonic diverticulosis, she takes Losartan more than 5 years (50 mg/day). As a consequence of severe osteoporosis she was assigned to fulllength recombinant PTH 1–84 (Preotact100 lg) subcutaneously plus 1000 mg elemental calcium and 800 IU vitamin D daily. Two months later she reported anemia (Hb: 8.8 g/dL, RBC: 3.58 M/ll, Ht:

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28,2%, MCV: 78,8 fL, MCH: 24,5 pg, MCHC: 31,1 g/dL, RDW: 13,8%; WBC: 5100/ml; PLT: 428000/dL). The patient was asymptomatic and thorough physical examination revealed no signs of anemia. It were excluded other causes of anemia (Table 1) and the patient underwent to bone marrow aspiration and biopsy that were normal. The anemia was attributed to PTH 1–84 and the medication was discontinued. Two months later, Ht and Hb were restored to normal values. The patient was assigned to weekly Alendronate plus 1000 mg elemental calcium and 800 IU vitamin D daily.

Table 1 Tests, radiologic images and endoscopic exams conducted to exclude other causes of anemia ESR

35

CPR (reference value: 0-5 mg/dL)

4.8

Alpha-1 acid glycoprotein (r.v: 0.3-120 mg/dL)

121

LDH (r.v.: 208-378 U/L)

220

Reticulocite (r.v.: 0.8-2.10%)

2

Serum iron (r.v.: 50-170 mcg/dL)

60

Ferritin (r.v.: 24-260 ng/mL)

250

Direct/Indirect Coombs

Negative

Total bilirubin (r.v.: 0.3-1.20 mg/dL)

0.2

Direct bilirubin (r.v.: 0.0-0.3 mg/dL)

0.05

Serum vitamin B12 (r.v.: 211-911 pg/mL)

382

Serum folic acid (r.v.: 3-14 ng/mL)

7.13

Beta-2 microglobulin (r.v.: 0.7-1.8) ANA

1.6 Negative

Abdomen contrast-enhanced -CT

Negative

Chest radiograph

Negative

Colonoscopy

Negative

Gastroscopy

Negative

Conclusion: Severe hyperparathyroidism (HPT), both primary (pHPT) and secondary (sHPT), may cause normochromic normocytic anemia. Parathyroidectomy has been reported to reverse anemia in pHPT and improve it in sHPT. A MEDLINE search up to present (May 2011) revealed one report of anemia resulting from treatment with either PTH 1–84 or PTH 1–34 (1). In the summary of product characteristics (SPC) of PTH 1–84, anemia is not reported as an AE; in the SPC of PTH 1–34, anemia is reported as a common AE without further details. The mechanism of anemia is unclear; marrow fibrosis caused by excess parathyroid hormone (PTH) has been proposed. Furthermore, in vitro studies showed no direct inhibitory effect of either PTH 1–84 or PTH 1–34 on animal and human hematopoietic progenitor growth. On the other hand, in another in vitro study PTH 1–84 exerted a negative effect in erythropoiesis. In our patient bone marrow aspiration and biopsy were normal, furthermore we do not know biochemical signals during recombinant human PTH induced anemia. In conclusion other studies are necessary to indagate the problem and monitoring Hb and Ht in PTH 1-84 and Teriparatide treated patients is advised. References 1. Anastasilakis AD, et al. J Bone Miner Metab. 2010;28(1):108–110

Pulmonary function evaluation in patients with rheumatoid arthritis treated with dmard’s classic or TNF a inhibitors: results of a retrospective analysis V.C. Rollo, M. Talia, A. Matarangolo, G. D’Alessandro Clinica Medica Azienda Ospedaliera Universitaria, Ospedali Riuniti Foggia. Centro studio malattie apparato osteoarticolare ed immunoproliferative, Italy Objective: Rheumatoid arthritis is a common inflammatory disease, affecting about 1% of the population, with female predominance. It is a systemic and autoimmune disease, characterized by symmetrical and erosive synovitis. Although the central pathology of rheumatoid arthritis develops within the synovium of diarthrodial joints, many non-articular organs become involved, infact extra-articular manifestations can be detected in almost all organ systems as cutaneous, ocular, hematological, cardiovascular and pulmonary lesions. In particular, with this study, we want to underline the correspondence between Rheumatoid arthritis and the small airways obstruction and to investigate the effects of different therapies on. Methods: We have recruited 28 patients (21 women and 7 men) from January to May 2011, that fulfill criteria of the American Rheumatoid Association for rheumatoid arthritis. Their mean age was about 58 years (range 40-75), and they were heterogeneous for smoking status (16 smoking, 12 non-smoking). These were also categorized according to their therapy into the following two sub-groups: 10 patients which received DMARD’s treatment (Methotrexate, Leflunomide, Hydroxychloroquine) and 18 which received TNFa9-inhibitors ones (Etanercept, Infliximab and Adalimumab). Pulmonary disorders were studied with spirometry, evaluating FEV1, FVC, FEV1/FVC, FEF 25-75%. Results: Analysis showed that a significant rate of patients had abnormal pulmonary function tests; more specifically 65% (18 patients)was affected by small airway obstruction and 7% (2 patients) by mixed respiratory involvement and 28% (8 patients) showed normal pulmonary function test. Among the patients with small airway obstruction, the 55% received TNFa9-inhibitors and the 45% DMARD’s treatment. In this study, smoking was not a confounding parameter, because the frequency of dysfunction was analogue between smoking and non-smoking (68% vs 58%). Conclusions: our experience shows that obstructive dysfunction of small airway is common among rheumatoid arthritis patients, confirming the literature we refer (from Collins’ ‘‘Obstructive pulmonary disease in rheumatoid arthritis’’ of 1976, and Geddes’ ‘‘Airways obstruction in rheumatoid arthritis’’ of 1979, to Fuld’s ‘‘). A longitudinal study of lung function in non-smoking patients with rheumatoid arthritis’’ of 2003, and Mori’s ‘‘Small airway obstruction in patients with rheumatoid arthritis’’ of 2010), and, besides, that this disease does not correlate with different kind of therapies or smoking status. Fever of unknown origin in ankylosing spondylitis E. Verrecchia, M. Giovinale, C. Fonnesu, A. Marinaro, R. Landolfi, R. Manna Periodic Fever Research Center, Internal Medicine Department. Catholic University of Sacred Heart, Rome, Italy The seronegative spondyloarthropathies are chronic inflammatory disorders characterized by articular manifestations and extra-articular symptoms. However in some cases, they may begin in an atypical way, only with fever of unknown origin (FUO).

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S392 We describe three patients which began with fever and then the final diagnosis was psoriatic arthritis in the first two patients and ankylosing spondylitis in the third one. In all these cases fever disappeared after treatment with anti-TNF drugs.

Two cases of hypercalcemia with different etiologies L. Castoldi§, M. Licini*, A. Coppini*, G. Bulgari§, M. Mazza§ § Clinica Medica Universita` degli Studi di Brescia; *II Medicina Interna Spedali Civili di Brescia Universita` degli Studi di Brescia, Italy

Hypercalcemia is a relatively common clinical problem. Different etiologies can cause increase in serum calcium concentrations. The parathyroid glands promote calcium homeostasis through a sensitive and complex self-regulating system. The intricacy and stability of this system are remarkable. Nonetheless, defects in vitamin D synthesis, mutations in the calcium-sensing receptor gene, insensitivity of the target organ, disturbances in the dietary intake of calcium, phosphorus and vitamin D and diseases of the parathyroid gland, liver and kidney may cause significant disorders in calcium homeostasis.We reported two cases admitted to our medical division with hypercalcemia of different origin. Case one: a 59 years old woman was admitted for epigastralgias, nausea, vomiting and thoracic pain. The patient’s medical history included a cronic gastritis in treatment with lansoprazole. Initial physical examination and hemodynamic parameters were normal. Basic blood chemistry showed a high serum calcium concentration of 15,18 mg/dl with 9,1 mg/dl of ionized calcium and an increase in serum creatinine (2,4 mg/dl),not previously reported, and in serum lipase (7965 U/L). The EKG showed a short QTc interval calculated at 0.34 s. The dosage of plasmatic 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D were elevated with a parathormone (PTH) clearly reduced. Treatment of hypercalcemia included hyperhydration, high doses of intravenous loop diuretics and zolendronate infusion. Hormonal, radiological, abdominal and cardiac investigations combined with a new parental interview led to the diagnosis of vitamin D intoxication due to excessive daily administration for a mistake in composition of officinal preparation. Pancreatitis required parenteral nutrition, antibiotic treatment and initial use of

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Intern Emerg Med (2011) 6 (Suppl 2):S191–S392 somatostatine with rapid resolution. At discharge her serum calcium level was 9 mg/dl. Case two: a 70-years old man was admitted with worsening weakness, drowsiness and an episode of lipothymia. The patient’s medical history included hypertension in treatment with amlodipine, chronic renal disease, benign prostatic hypertrophy and a recent pleuropneumonia. Physical examination was normal. Basic blood chemistry showed a high serum calcium concentration of 16 mg/dl with 8,0 mg/dl of ionized calcium. Thyroid function was normal. The dosage of PTH was extremely elevated (849 pg/ml; n.r. 11-67 pg/ml). Neck’s ultrasound scan showed a nodule in the right lobe of thyroid gland, suspected for parathyroid adenoma and then confirmed by scintigraphy. Treatment of hypercalcemia included hyperhydration, intravenous loop diuretics and pamidronate infusion. Later the patient underwent surgery (inferior right parathyroidectomy) that required also right emithyroidectomy for the discover of a thyroid nodule. Histology confirmed parathyroid adenoma and showed a non medullary thyroid carcinoma. For this reason he underwent radical thyroidectomy after one month. At discharge his serum calcium level was 8,8 mg/dl. Discussion: Hypercalcemia could be a serious and possible lifethreatening problem, causing acute renal insufficiency and pancreatitis. Over a promt treatment, facing a patient with repeatedly elevated serum calcium levels, there is the necessity to evaluate different etiologies. Anamnesis could be clarifying, in particular paying attention to every drug and medication the patient is taking. Initial drug-taking history in the first case described did not reveal the use of over-thecounter supplements, which underlines the importance of a thorough evaluation of non prescribed medication. Moreover, these supplements may contain higher levels of vitamin D than the label states. That’s the reason why dosage should be carefully evaluated, and if officinal preparations are used, it should be focused on concentration of calcium and vitamin D and possible mistaken in concentration, as in the first case reported. If calcipherol dosage is normal, the most common causes of hypercalcemia are hyperparathyroidism and malignant conditions. Considering the former etiology, we want to focus on the possibility, already cited in a small series of reports in the literature, of a coexistent primary hyperparathyroidism and thyroid carcinoma, but not-medullary, as in the second case reported. This represents a condition of hypercalcemia due to parathyroid dysfunction but with a parallel neoplasm, not related to MEN, but in which hypercalcemia could be the key to make an early diagnosis and treatment of a thyroid carcinoma.