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BACKGROUND: Postmastectomy radiotherapy was shown in previous meta-analyses to reduce the risks of both recurrence and breast cancer mortality in all women with node-positive disease considered together. However, the benefit in women with only one to three positive lymph nodes is uncertain. We aimed to assess the effect of radiotherapy in these women after mastectomy and axillary dissection.METHODS: We did a meta-analysis of individual data for 8135 women randomly assigned to treatment groups during 1964-86 in 22 trials of radiotherapy to the chest wall and regional lymph nodes after mastectomy and axillary surgery versus the same surgery but no radiotherapy. Follow-up lasted 10 years for recurrence and to Jan 1, 2009, for mortality. Analyses were stratified by trial, individual follow-up year, age at entry, and pathological nodal status.FINDINGS: 3786 women had axillary dissection to at least level II and had zero, one to three, or four or more positive nodes. All were in trials in which radiotherapy included the chest wall, supraclavicular or axillary fossa (or both), and internal mammary chain. For 700 women with axillary dissection and no positive nodes, radiotherapy had no significant effect on locoregional recurrence (two-sided significance level [2p]>0·1), overall recurrence (rate ratio [RR], irradiated vs not, 1·06, 95% CI 0·76-1·48, 2p>0·1), or breast cancer mortality (RR 1·18, 95% CI 0·89-1·55, 2p>0·1). For 1314 women with axillary dissection and one to three positive nodes, radiotherapy reduced locoregional recurrence (2pINTERPRETATION: After mastectomy and axillary dissection, radiotherapy reduced both recurrence and breast cancer mortality in the women with one to three positive lymph nodes in these trials even when systemic therapy was given. For today's women, who in many countries are at lower risk of recurrence, absolute gains might be smaller but proportional gains might be larger because of more effective radiotherapy.FUNDING: Cancer Research UK, British Heart Foundation, UK Medical Research Council.

Background: Intracellular calcium is essential for muscle cells contrac- tion. Several drugs such as amines and levosimendan increase inotropism by acting directly or indirectly on intracellular calcium levels or sensitiv- ity. Serum calcium levels (SCL) are not directly correlated to intracellular calcium concentration, but a reduced gradient could influence intracellular concentrations. For this reason, we aimed to evaluate whether SCL could be related to in-hospital survival among patients affected by acute heart failure. Materials and Methods: 216 consecutive patients admitted to our Internal Medicine Department (IMD) for acute heart failure were retrospectively enrolled. In-hospital mortality and comorbidities (hypertension, diabetes, atrial fibrillation, chronic heart failure, acute coronary syndrome, COPD, sepsis, chronic kidney disease and cancer) were collected as binary vari- ables. Days of hospitalization were treated as continuous data. SCL were synthesized as an ordinal variable (25% low percentile, 50% middle percen- tile and 25% high percentile).Cox regression model was set up to evaluate the role of serum calcium levels on in-hospital mortality inserting in the model all the comorbidities, days of hospitalization, age and sex as covari- ates. Statistic was performed with SPSS 13.0 for Windows Systems. Results: Mean age was 80 years (±12,55 years), with M:F ratio of 1:1 (males 52.7%). Diabetes was present in 23,1%, hypertension in 34,3%, ac- tive cancer in 8,8%, atrial fibrillation in 30,1%, chronic ischemic cardiopa- thy in 28,2%, acute coronary syndrome in 12,5%, congestive heart failure in 42,6%, COPD in 18,1%, sepsis in 1,4%, chronic kidney disease in 18,5% of the sample. 13,4% of the sample died during the admission. Mean of the days of hospitalization was of 12,65 days (±8,28 days). In the Cox model, correcting for all the above-mentioned covariates, serum calcium levels taken at the admission behaved as an independent risk factor for in-hospital death (Figure 1). Lower or normal serum calcium levels were associated to a higher risk of in-hospital mortality (OR: 8,308; 95%CI:1,075-64,21; p

Introduction: The Sequential Organ Failure Assessment (SOFA) Score is a score validated to assess prognosis in septic patients. The initial SOFA score predicts in-hospital mortality: values above 11 are correlated with a mortal- ity more than 80%. Troponin I (TnI) is a marker of myocardial injury, but its role in sepsis is still controversial: it has been supposed that TnI could iden- tify patients with a worse prognosis. We aimed to evaluate if adding TnI to SOFA score resulted in a better prognostic performance in the septic patient. Materials and Methods: 81 patients affected by severe sepsis or septic shock and admitted to our Internal Medicine Department were enrolled. For each patient, SOFA score and serum TnI, procalcitonin (PCT), C-reactive protein (CRP) were evaluated at the admission. Outcome was defined as in-hospital death, and collected as a binary variable. TnI was recorded both as a continuous and as a dichotomous variable (≤0.05 or >0.05 ng/ml). Age and days of in-hospital admission were collected as continuous variables. Sex was treated as dichotomous. SOFA score was synthesized as an ordi- nal variable, considering partial pressure of oxygen, fraction of inhaled O2, platelet count, Glasgow coma scale, serum bilirubin and creatinine and the degree of hypotension (1) as single items of the scale. SOFA-T was calcu- lated adding 1 point to SOFA score if TnI levels were higher than 0.05 ng/ ml. The difference in levels of TnI between survivors and non survivors was analyzed with a Univariate/GLM including SOFA, CRP, PCT, age, sex and days of admission as covariates. ROC curve analysis was performed considering SOFA and SOFA-T to predict the main outcome. Analysis was performed with SPSS 13.0 for Windows systems. Results: Mean age was 77,7±11,24 years, males representing 53,8% of the sample. 33,8% of the patients died during the hospitalization. Mean SO- FA score was 6,42±3,24. The mean days of admission were 16,07±10,25. TnI had a mean concentration of 2,31±7,14 ng/ml, PCT 11,51±21,33 pg/ ml, CRP 14,96±11,1 mg/dl. At univariate/GLM model estimated mean TnI level was 1,028 ng/ml (SE: 0,722) among survivors, while it was 4,779 ng/ ml (SE:1,243) among non survivors, and this difference was statistically Figure 1. ROC curve analysis in predicting in-hospital death for patients with sepsis with SOFA or SOFA-T score significant (p

Background: Seric uric acid (SUA) is the final product of purine metabo- lism, known as the cause of gout and uratic nephropaty. In the last decades many studies have been performed to investigate its role as a cardio-vascu- lar risk factor and today literature defines SUA as a controversial protective antioxidant resource against cardiovascular diseases that seems to lose this role both in case of lower SUA levels and in hyperuricemia, when antioxi- dant activity is imbalanced into the field of oxidant injury. Methods: We retrospectively collected data from 651 patients with acute stroke followed during the period between 2011 and 2013. Mean age of the sample was 79 years, males represented 47,6%; patients affected by chronic kidney disease were 47.5%. Results: The duration of hospitalization for acute stroke, when related to SUA levels, showed a J-curve distribution, with longer admissions observed among patients with both lower (7 mg/dl) SUA levels (Fig.1). Kaplan-Meier’s curve showed that patients with levels between 4.5 and 7.0 mg/dl had a significantly better in-hospital survival than patients with low SUA levels ( 7 mg/dl), as shown in Fig.2 (p

8th Congress of the Pan-Asian-Committee-for-Research-and-Treatment-of-Multiple-Sclerosis (PACTRIMS) -- NOV 19-21, 2015 -- Seoul, SOUTH KOREA Belachew, Shibeshih/0000-0003-3976-1950; Horakova, Dana/0000-0003-1915-0036; Lugaresi, Alessandra/0000-0003-2902-5589; Havrdova, Eva Kubala/0000-0002-9543-4359; WOS: 000372242400086 … Pan Asian Comm Treatment & Res Multiple Sclerosis

32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) -- SEP 14-17, 2016 -- London, ENGLAND Havrdova, Eva Kubala/0000-0002-9543-4359; Lugaresi, Alessandra/0000-0003-2902-5589; Horakova, Dana/0000-0003-1915-0036 WOS: 000383267202355 … European Comm Treatment & Res Multiple Sclerosis Biogen IncBiogen; NovartisNovartis; Bayer Vital GmbHBayer AG; Biogen IdecBiogen; Merck SeronoMerck SeronoMerck & Company; Sanofi GermanySanofi-Aventis; Sanofi US; Acorda; Actelion; Allozyne; BaroFold; Bayer HealthCareBayer AGBayer Healthcare Pharmaceuticals; Bayer ScheringBayer AG; Bayhill Therapeutics; Elan; European UnionEuropean Union (EU); Genmab; Gianni Rubatto Foundation; GlaxoSmithKlineGlaxoSmithKline; Glenmark; MediciNova; Novartis Research Foundation; RocheRoche Holding; Roche Research Foundation; Sanofi-AventisSanofi-Aventis; Santhera; Swiss MS Society; Swiss National Research FoundationSwiss National Science Foundation (SNSF); Teva Neuroscience; UCBUCB Pharma SA; WyethWyeth; SanofiSanofi-Aventis; Teva; GenzymeGenzyme Corporation; BayerBayer AG; BiogenBiogen; Fondazione Italiana Sclerosi MultiplaFondazione Italiana Sclerosi Multipla (FISM); EMD SeronoMerck Serono; CIHRCanadian Institutes of Health Research (CIHR); MS Society of Canada; Teva-Neuroscience; Canadian Multiple sclerosis society; Bayer Health CareBayer AGBayer Healthcare Pharmaceuticals; CSL; Genzyme SanofiGenzyme Corporation; Almirall; Sanofi AventisSanofi-Aventis; Associazione Marchigiana Sclerosi Multipla e altre malattie neurologiche Tim Spelman received compensation for serving on scientific advisory boards, honoraria for consultancy and funding for travel from Biogen Inc; speaker honoraria from Novartis.; Heinz Wiendl received compensation for serving on scientific advisory boards for Bayer Healthcare, Biogen Idec, Genzyme, Merck Serono, Novartis, and Sanofi; speaker honoraria and travel support from Bayer Schering AG, Bayer Vital GmbH, Biogen Idec, CSL Behring, Fresenius Medical Care, Genzyme, GlaxoSmithKline, GW, Merck Serono, Novartis, and Sanofi; compensation as a consultant from Biogen Idec, Merck Serono, Novartis, and Sanofi; research support from Bayer Vital GmbH, Biogen Idec, Merck Serono, Novartis, Sanofi Germany, and Sanofi US.; Ludwig Kappos received research support from Acorda, Actelion, Allozyne, BaroFold, Bayer HealthCare, Bayer Schering, Bayhill Therapeutics, Biogen Idec, Elan, European Union, Genmab, Gianni Rubatto Foundation, GlaxoSmithKline, Glenmark, MediciNova, Merck Serono, Novartis, Novartis Research Foundation, Roche, Roche Research Foundation, Sanofi-Aventis, Santhera, Swiss MS Society, Swiss National Research Foundation, Teva Neuroscience, UCB, and Wyeth.; Guillermo Izquierdo received consulting fees from Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi, and Teva.; Eva Havrdova received speaker honoraria and consultant fees from Biogen Idec, Merck Serono, Novartis, Genzyme and Teva, as well as support for research activities from Biogen Idec and Merck Serono.; Alessandra Lugaresi was a Bayer, Biogen, Genzyme, Merck Serono, Novartis Advisory Board Member. She received travel grants and honoraria from Bayer, Biogen, Merck Serono, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla, her Institution received research grants from Bayer, Biogen, Merck Serono, Novartis, Sanofi, Teva and Fondazione Italiana Sclerosi Multipla.; Pierre Duquette has received honoraria for organising CME events and has obtained funding to attend meetings from Biogen Idec, EMD Serono, TEVA Neuroscience, Novartis, and Genzyme, has received funding for investigator-initiated trials with Biogen Idec, EMD Serono and Novartis, and has received peer-review funding from CIHR and from the MS Society of Canada.; Pierre Grammond is a Novartis, Teva-neuroscience, Biogen Idec advisory board member, consultant for Merck Serono, received payments for lectures by Merck Serono, Teva-Neuroscience and Canadian Multiple sclerosis society, and received grants for travel from Teva-Neuroscience and Novartis.; Jeannette Lechner-Scott has accepted travel compensation from Novartis, Biogen and Merck Serono. Her institution receives the honoraria for talks and advisory board commitment and also clinic support from Bayer Health Care, Biogen, CSL, Genzyme Sanofi, Merck Serono, Novartis and TEVA.; Franco Granella has served on scientific advisory boards for Biogen Idec, Novartis and Sanofi Aventis and has received funding for travel and speaker honoraria from Biogen Idec, Merck Serono, and Almirall.; Eugenio Pucci served on scientific advisory boards for Genzyme, Novartis and Biogen-Idec; he has received honoraria and travel grants from Sanofi Aventis, Novartis, Biogen Idec, Merck Serono, Genzyme and Teva; he has received travel grants from Associazione Marchigiana Sclerosi Multipla e altre malattie neurologiche.; Helmut Butzkueven received honoraria for consultancy and/or speaking from Biogen Idec, Genzyme-Sanofi, Merck Serono, Novartis, and Roche; research grants from Biogen Idec, Merck Serono, Novartis, and Teva.

Background: There are a few and conflicting results from randomised controlled trials (RCTs) pertaining to the influence of gender in response to currently used disease modifying drugs in Multiple Sclerosis (MS). Observational studies may be especially valuable for answering effectiveness questions in subgroups not studied in RCTs. Objective: To conduct a post-marketing analysis aimed to evaluate the gender effect on Interferon beta (IFN beta) treatment response in a cohort of relapsing (RR) MS patients. Methods: A cohort of 2570 IFN beta-treated RRMS was prospectively followed for Lip to 7 years in 15 Italian MS Centers. Cox proportional hazards regression models were used to assess gender differences for risk of reaching 1st relapse and risk of progression by I point on Expanded Disability Status Scale (EDSS) score. Gender effects were also explored by a propensity score (PS) matching algorithm, and a tree-growing technique. Results: The multivariate Cox Regression analyses showed that male patients had a significant (p = 0.0097) lower risk for 1st relapse and a trend (p = 0.0897) for a higher risk to reach I point EDSS progression than females. The PS matched multivariate Cox Regression confirmed these results. The RECPAM analysis showed that male sex conferred a significant reduction in the risk for 1st relapse (HR = 0.86; 95% Cl = 0.76-0.98; p = 0.0226) in the subgroup with a low pre-treatment number of bouts, and a significant increase in the risk for I point EDSS progression (HR = 1.33; 95% Cl: 1.00-1.76; p

OBJECTIVE: Recent findings support greater efficacy of early vs. delayed interferon beta (IFNbeta) treatment in patients with a first clinical event suggestive of multiple sclerosis (MS). We aimed to evaluate the effectiveness of early IFNbeta treatment in definite relapsing-remitting MS (RRMS) and to assess the optimal time to initiate IFNbeta treatment with regard to the greatest benefits on disability progression. METHODS: A cohort of 2,570 IFNbeta-treated RRMS patients was prospectively followed for up to 7 years in 15 Italian MS Centers. A Cox proportional hazards regression model adjusted for propensity score (PS) quintiles was used to assess differences between groups of patients with early vs. delayed IFNbeta treatment on risk of reaching a 1-point progression in the Expanded Disability Status Scale (EDSS) score, and the EDSS 4.0 and 6.0 milestones. A set of PS-adjusted Cox hazards regression models were calculated according to different times of treatment initiation (within 1 year up to within 5 years from disease onset). A sensitivity analysis was performed to assess the robustness of findings. RESULTS: The lowest hazard ratios (HRs) for the three PS quintiles-adjusted models were obtained by a cutoff of treatment initiation within 1 year from disease onset. Early treatment significantly reduced the risk of reaching a 1-point progression in EDSS score (HR = 0.63; 95% CI = 0.48-0.85; p < 0.002), and the EDSS 4.0 milestone (HR = 0.56; 95% CI = 0.36-0.90; p = 0.015). Sensitivity analysis showed the bound of significance for unmeasured confounders. INTERPRETATION: Greater benefits on disability progression may be obtained by an early IFNbeta treatment in RRMS.

OBJECTIVE—To evaluate the impact of a continuous quality improvement effort implemented by a network of diabetes outpatient clinics in Sicily, Italy. RESEARCH DESIGN AND METHODS—Twenty-two clinics adopted the same electronic medical record system. Process and intermediate outcomes indicators were identified and software was developed, enabling the extraction of the information needed for the profiling of quality of care. Data were centrally analyzed anonymously every year, and results were discussed in meetings with the participants. The performances of the different centers were ranked against the “best performers,” and the reasons for variation were discussed. RESULTS—From 2001 to 2005, a total of 26,782 patients aged ≥18 years have been seen in the participating clinics. Rates of monitoring of A1C, blood pressure, lipid profile, and microalbuminuria constantly increased over the years. The percentage of individuals with A1C values ≤7.0% increased by 16.6%, while the proportion of patients with blood pressure ≤130/85 mmHg increased by 10.7%. The percentage of individuals with LDL cholesterol levels CONCLUSIONS—We found a strong consistency between increasing rates of monitoring, increasing drug prescription, and better levels of intermediate outcomes. Despite the satisfactory achievements, a substantial room for improvement in the care of diabetes still persists.

Objective: To investigate the quality of type 2 diabetes care according to sex. RESEARCH DESIGN AND METHODS: Clinical data collected during the year 2009 were extracted from electronic medical records; quality-of-care indicators were evaluated. Multilevel logistic regression analysis was applied to estimate the likelihood of women versus men to be monitored for selected parameters, to reach clinical outcomes, and to be treated with specific classes of drugs. The intercenter variability in the proportion of men and women achieving the targets was also investigated. RESULTS: Overall, 415,294 patients from 236 diabetes outpatient centers were evaluated, of whom 188,125 (45.3%) were women and 227,169 (54.7%) were men. Women were 14% more likely than men to have HbA1c>9.0% in spite of insulin treatment (odds ratio 1.14 [95% CI 1.10-1.17]), 42% more likely to have LDL cholesterol (LDL-C)≥130 mg/dL (1.42 [1.38-1.46]) in spite of lipid-lowering treatment, and 50% more likely to have BMI≥30 kg/m2 (1.50 [1.50-1.54]). Women were less likely to be monitored for foot and eye complications. In 99% of centers, the percentage of men reaching the LDL-C target was higher than in women, the proportion of patients reaching the HbA1c target was in favor of men in 80% of the centers, and no differences emerged for blood pressure. CONCLUSIONS: Women show a poorer quality of diabetes care than men. The attainment of the LDL-C target seems to be mainly related to pathophysiological factors, whereas patient and physician attitudes can play an important role in other process measures and outcomes

BACKGROUND/OBJECTIVES:Dietary habits are important determinants of individual cardiovascular and metabolic risk. This study investigated the association between dietary patterns and asymptomatic carotid atherosclerosis, defined as the presence of plaques and/or increased intima-media thickness, and metabolic biomarkers of insulin resistance, including the homeostasis model assessment of insulin resistance (HOMA-IR) and the trygliceride/high-density lipoprotein (HDL)-cholesterol (Tg/HDL) ratio in a cohort of adults without known diabetes or atherosclerotic cardiovascular disease.SUBJECTS/METHODS:Nine hundred and twenty-nine randomly selected participants were cross-sectionally investigated. Each participant answered a food frequency questionnaire, and underwent high-resolution ultrasonographic evaluation of both carotid arteries. Laboratory blood measurements were obtained in a subsample of 507 participants.RESULTS:A dietary pattern that could be defined as unhealthy (high consumption of soft drinks, fried foods, seed oils, cured meats, butter, red meat and sweets) was identified in 21% of the cohort, whereas 34% of the cohort exhibited a dietary pattern that resembled the Mediterranean diet (high intakes of fruit, milk and cheese, olive oil, vegetables, pasta and bread). Intermediate habits characterized the remaining 45%. After adjusting for age, body mass index (BMI), waist circumference, glycated hemoglobin (HbA1c) and hypertension on treatment, the Mediterranean dietary pattern was associated with significantly lower HOMA-IR (β-coefficient=-0.51; P=0.003). After adjusting for gender, BMI and HbA1c, the unhealthy dietary pattern was associated with a significantly higher Tg/HDL-cholesterol ratio (β-coefficient=0.43; P=0.006). No significant association was found between dietary patterns and carotid atherosclerosis.CONCLUSIONS:This study suggests that, independent of measures of adiposity, a Mediterranean dietary pattern is associated with lower insulin resistance.

Introduction: Sepsis and septic shock are severe medical conditions,often observed in Internal Medicine Departments (IMD). Even if not recognized by some authors as an additional risk factor, troponin I (TnI) could be an early marker of cardiac microvessels derangement and septic cardiomyopathy,but is not included in the common scores used to assess prognosis. Objective: To examine association between SOFA-score and TnI in a retrospective cohort of septic patients. Methods: We retrospectively collected data from patients’ files treated in our IMD for severe sepsis/septic shock. Age,sex,SOFA-score,TnI and in-hospital death were considered for the analysis. TnI was treated as binary(cutoff 0.08ng/ml),while SOFA-score was analyzed both as an ordinal variable and a binary variable(cutoff at 9 points). The relationship between SOFA-score and the risk of in-hospital death was analyzed with CHi-squared statistic. The association between SOFA-score and TnI was assessed with an ordinal regression model using a complementary log-log link function. Accounting of age and sex as covariates, we obtained a significant model(p9 points)resulted significantly associated with an increased risk of in-hospital death(OR=3.00;95%CI 1.10-9.30;p

31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) -- OCT 07-10, 2015 -- Barcelona, SPAIN Lugaresi, Alessandra/0000-0003-2902-5589; Horakova, Dana/0000-0003-1915-0036; Havrdova, Eva Kubala/0000-0002-9543-4359; Belachew, Shibeshih/0000-0003-3976-1950; WOS: 000365729400450 … European Comm Treatment & Res Multiple Sclerosis

Background and aims Metformin is the first-line therapy in type 2 diabetes. In patients inadequately controlled with metformin, the addition of a sulfonylurea or pioglitazone are equally plausible options to improve glycemic control. However, these drugs have profound differences in their mechanism of action, side effects, and impact on cardiovascular risk factors. A formal comparison of these two therapies in terms of cardiovascular morbidity and mortality is lacking. The TOSCA.IT study was designed to explore the effects of adding pioglitazone or a sulfonylurea on cardiovascular events in type 2 diabetic patients inadequately controlled with metformin. Methods Multicentre, randomized, open label, parallel group trial of 48 month duration. Type 2 diabetic subjects, 50–75 years, BMI 20–45 Kg/m 2 , on secondary failure to metformin monotherapy will be randomized to add-on a sulfonylurea or pioglitazone. The primary efficacy outcome is a composite endpoint of all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, and unplanned coronary revascularization. Principal secondary outcome is a composite ischemic endpoint of sudden death, fatal and non-fatal myocardial infarction and stroke, endovascular or surgical intervention on the coronary, leg or carotid arteries, major amputations. Side effects, quality of life and economic costs will also be evaluated. Efficacy, safety, tolerability, and study conduct will be monitored by an independent Data Safety Monitoring Board. End points will be adjudicated by an independent external committee. Conclusions TOSCA.IT is the first on-going study investigating the head-to-head comparison of adding a sulfonylurea or pioglitazone to existing metformin treatment in terms of hard cardiovascular outcomes. Registration: Clinicaltrials.gov ID NCT00700856.

Objective The European Acquired Haemophilia registry (EACH2) collected data on the demographics, diagnosis, underlying disorders, bleeding characteristics, treatment, and outcome of women with acquired haemophilia A (AHA), a rare and often severe bleeding disorder caused by autoantibodies directed against coagulation factor VIII. Design Prospective, multi-centre, large-scale, pan-European registry. Setting A total of 117 haemophilia centres in 13 European countries. Population Pregnancy-associated AHA. Methods Data were reported using a web-based electronic case report form. Diagnosis was based on the presence of a prolonged activated partial thromboplastin time, reduced coagulation Factor VIII level and positive inhibitor assay. Main outcome measures Presenting characteristics, time to diagnosis, haemostatic treatment and outcome, immunosuppressive treatment and outcome. Results The EACH2 registry (n = 501) documented 42 (8.4%) cases of AHA associated with the peripartum period, a median Factor VIII level at diagnosis of 2.5 (range 0-25) IU/dl and inhibitor titre of 7.8 (range 0.7-348) BU/ml. Antepartum inhibitors were evident in eight women. Time to diagnosis of AHA after delivery was 89 (range 21-120) days. First-line haemostatic treatment was successful in 20/23 (87%) women treated. Bleeding episodes resolved in 17/18 (94%) women treated with a bypassing agent and 29/39 (74%) women achieved complete remission with first-line immunosuppressive treatment. Two babies experienced postnatal bleeding, suggesting transplacental transfer of the antibody. All women were alive at last follow-up. Conclusions Although rare, pregnancy-associated AHA may cause severe bleeding-related morbidity. Once diagnosed, women respond well to haemostatic treatment with bypassing agents and immunosuppression. Awareness of peripartum AHA requires improvement to facilitate rapid and appropriate management.

Background: Levosimendan is a pyridazone-dinitrile derivative. Its primary action is to increase cardiac contractility: binding to troponin C in a calcium-dependent manner and stabilizing it, levodimendan induces actomyosin cross-bridging without increasing myocardial consumption of adenosine triphosphate (ATP) or intracellular calcium concentration. Thus, cardiac performance and contractility are improved with no increase in the total myocardial energy demand and oxygen consumption. Exerting its effects mainly during systole, regular ventricular filling and coronaric flow are preserved in dyastole. Moreover, arrhytmogenesis is not increased as total intracellular calcium levels are not raised. Levosimendan’s peripheral actions are mainly related do vasodilatation, with reduction of cardiac afterload. Independent to the beta-adrenergic pathway, levosimendan increases cardiac inotropism, reduces peripheral vasoconstriction even in presence of the beneficial effects of beta-blockade. Clinical trials have already evaluated the potential clinical application of this drug in acute decompensated heart failure (AHF), without being conclusive for a definite beneficial effect of levosimendan on major outcomes over classic inotropic drugs, such as beta-agonists [1, 2], actually representing an expensive, secondline option in this setting. On the other hand, only small, nonrandomized studies have evaluated the role of the pulsed i.v. administration of this drug in patients affected by chronic heart failure (CHF) with low ejection fraction [3, 4]. To our knowledge, one RCT has been performed on a the oral formulation of levosimendan in this setting [5], and a larger trial on the i.v. pulsed administration is still ongoing [6]. Aims of the study: To describe how pulsed, chronic i.v. administration of levosimendan affected survival, funtional class, number of admissions due to AHF and ejection fraction in ten patients with chronic, compensated heart failure followed by our Internal Medicine department. Materials and methods: Ten consecutive male patients, homogeneous for pathology (postischemic hypertrophic-dilated cardiopathy) and functional class (NYHA class IIIB-IV) were selected for pulsed administration of levosimendan, 0.15 lg/kg/min every 3 weeks starting from 01/01/2007. History and physical examination were performed every admission. Echocardiography and BNP were performed at the time of the first infusion and every 3 months. Statistical analysis was performed with SPSS 13.0 for Windows. Results: Mean age of the group was 76 ± 12 years. All the patients were under therapy with beta-blocker, an ACE-I or an ARB, loop diuretics, spironolactone or similar anti-aldosteronic drugs and statins. Two patients died for acutely decompensated heart failure (32 and 14 months, respectively, after the first infusion). 40% of the group needed further admissions for acutely decompensated heart failure. Mean survival of the group was 25.6 ± 16.5 months. Ejection fraction was 30.8 ± 6.2% at baseline and increased to 40 ± 5.9% at 3 months (p\0.05, using Wilcoxon Signed rank test and t test for repeated measures). BNP mean level was 718. ± 227.2 ng/ml at baseline and decreased to 503 ± 159.3 ng/ml at 3 months (p\0.05, using Wilcoxon Signed rank test and t test for repeated measures). NYHA class remained constant within the controls (p[0.05 using Chi-squared test). Discussion: In this small case series, survival and rehospitalization rates were lower than the ones described in literature [7]. We also observed an overall improvement of echocardiographic and laboratoristic parameters in patients undergoing to levosimendan therapy. Since large, randomized, studies of the use of this drug in chronic, compensated heart failure are still ongoing [6], our data are only suggestive fore possible a role of i.v. administration of levosimendan in manteinance therapy in CHF. These data are consistent with those already described in other studies [3, 4]. References 1. Follath F, Cleland JG et al (2002) Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised doubleblind trial. Lancet 360(9328):196–202 2. Mebazaa A, Nieminen MS et al (2007) Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE randomized trial. JAMA 297(17):1883–1891 3. Nanas JN, Papazoglou P et al (2005) Efficacy and safety of intermittent, long-term, concomitant dobutamine and levosimendan infusions in severe heart failure refractory to dobutamine alone. Am J Cardiol 95(6):768–771 4. Drakos SG, Kanakakis JV et al (2009) Intermittent inotropic infusions combined with prophylactic oral amiodarone for patients with decompensated end-stage heart failure. J Cardiovasc Pharmacol 53(2):157–161 (PubMed PMID: 19188832) 5. Nieminen MS, Cleland JG et al (2008) Oral levosimendan in patients with severe chronic heart failure—the PERSIST study. Eur J Heart Fail 10(12):1246–1254 (Epub 2008 Oct 21) S92 Intern Emerg Med (2010) 5 (Suppl 2):S91–S128 123 6. Altenberger J, Parissis JT, Ulmer H, Poelzl G, LevoRep Investigators (2010) Rationale and design of the multicentre randomized trial investigating the efficacy and safety of pulsed infusions of levosimendan in outpatients with advanced heart failure (LevoRep study). Eur J Heart Fail 12(2):186–192 7. Fauci AS, Braunwald E et al (1998) Harrison’s Principles of Internal Medicine, 17th edn. McGraw-Hill, New York This contribution has been awarded as Best Communication.

Background: Atherosclerosis is a systemic process, involving multiple arterial districts at the same time. Carotid doppler ultrasound is an easy and non-invasive test, able to evaluate the layers of the neck arteries and the involvement of this district in the atherosclerotic process. Carotid intima-media-thickness (IMT) is known to be a marker of the systemic atherosclerotic process. Dopper ultrasound could become useful, allowing a correct risk stratification in the systemic involvement by the atherosclerotic process. Moreover, it could be functional, in association with the other already-validated rulers, in targeting the best therapeutic choice for acute coronary heart disease [6]. An increase of IMT or the presence of atherosclerotic plaque in asymptomatic patients have been associated to an increased risk for coronary heart disease (CHD) in large, perspective studies [1–4]. On the other hand, a recent meta-analysis [5] showed that neither the presence of an increased IMT neither the presence of a plaque were discriminatory enough to be considered a reliable screening test among patients with symptomatic CHD. Aims of the study: To evaluate a correlation between carotid arteries ultrasonographic pattern and coronaric pathology extension among symptomatic CHD patients living in our region. Materials and methods: In the period 01/2007–01/2008, we enrolled 100 consecutive patients admitted to our Internal Medicine Department for acute coronary syndrome (ACS). For each patient, we evaluated the classical risk factors (familiarity, known CHD, diabetes mellitus, dyslipidemia, hypertension, smoke and obesity), the extent of the atherosclerotic pathology (cerebrovascular events, peripheral arteries pathology and CHD) and the therapy at the moment of the admission. Every subject underwent to doppler ultrasound: IMT, presence of carotid plaque and degree of stenosis were evaluated. Coronarographic assessment evaluated the number of arteries with significant obstruction, the total coronary score (TCS), the site and the degree of stenosis. We performed the statistical analysis with SPSS 13.0 package for Windows systems. Results: The absence of a previous history of CHD and a negative carotid ultrasound (normal IMT, no evidence of any plaque) were the strongest protective factors for multiple-vessel coronary disease (CHD: OR = 0.132; 95% CI 0.027–0.628, p\0.05; Negative US: OR = 0.223; 95% CI: 0.067–0.742, p\0.05). Lower percentages of stenosis were associated to lower TCS as detected at coronarography (0–30% stenosis at US: OR = 6.76 [95% CI: 19.25–2.37, p\0.05] of obtaining a low TCS) with a decrease of the risk of low TCS with proportional to the increase of carotid stenosis. Discussion: In this small, retrospective analysis we correlate a normal carotid ultrasonographic pattern with a low risk of multiple-vessel involvment at coronarography. Moreover, in this population of symptomatic patients, we correlate the percentage of carotid stenosis with a proportional increase of the risk of an higher TCS at coronarography. These data suggest that among high-risk, symptomatic patients, carotid ultrasound and doppler evaluation can be a reliable indicator of the extent of coronary pathology. References 1. Simon A, Chironi G, Levenson J (2007) Comparative performance of subclinical atherosclerosis tests in predicting coronary heart disease in asymptomatic individuals. Eur Heart J 28(24):2967–2971 (review) 2. Chambless LE, Heiss G, Folsom AR, Rosamond W, Szklo M, Sharrett AR, Clegg LX (1997) Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987–1993. Am J Epidemiol 146:483–494 3. O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr (1999) Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med 340:14–22 4. Salonen T, Salonen R (1991) Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arterioscler Thromb 11:1245–1249 5. Wald DS, Bestwick JP (2009) Carotid ultrasound screening for coronary heart disease: results based on a meta-analysis of 18 studies and 44,861 subjects. J Med Screen 16(3):147–154 6. Flu WJ, van Kuijk JP, Hoeks SE, Kuiper R, Schouten O, Goei D, Winkel T, van Gestel YRBM, Verhagen HJM, Bax JJ, Poldermans D, Rotterdam, and Leiden, The Netherlands, Coronary Artery Disease Intima media thickness of the common carotid artery in vascular surgery patients: a predictor of postoperative cardiovascular events

AIMS: We evaluated the impact of a continuous quality improvement effort implemented by a network of Italian diabetes clinics operating in the national healthcare system. METHODS: This was a controlled before-and-after study involving 95 centres, of which 67 joined the initiative since 2004 (group A) and 18 were first involved in 2007 (group B, control). All centres used electronic medical record systems. Information on quality indicators was extracted for the period 2004-2007. Data were centrally analysed anonymously and results were published annually. Each centre's performance was ranked against the 'best performers'. We compared quality indicators between the two groups of centres over 4 years. RESULTS: Over 100 000 Type 2 diabetes mellitus patients were evaluated annually. The proportion of patients with glycated haemoglobin levels < 7% increased by 6% in group A (2007-2004 difference) and by 1.3% in group B. The proportion of patients with low-density lipoprotein-cholesterol < 100 mg/dl improved by over 10% in both groups. The rate of patients with blood pressure values < or = 130/85 mmHg increased in group A (+6.4%), but not in group B (-1.4%). The use of insulin increased in group A only (+5.2%), while the use of statins increased by over 20% in both groups. CONCLUSIONS: A physician-led quality improvement effort, based on the systematic evaluation of routine data, is effective in improving the performance of a large number of diabetes clinics. The small percentage increase in the number of patients at target, if applied to large numbers of patients, would translate into a significant impact on public health.

Case report: We report a case of two successful pregnancies in a patient with a prior diagnosis of essential thrombocytemia with secondary portal vein thrombosis and portal hypertension. A 19-year-old woman affected by undefined thrombocytosis (platelets count 650,000 mmc-1) since 1990 was admitted to our department in May 1995 for severe abdominal pain and hepatosplenomegaly. History was negative for smoking or autoimmune disorders and laboratoristic exams showed a slight increase of leukocytes, erythrocytes, hemoglobin, transaminases, bilirubin, and decreased PT. Portal hypertension secondary to inferior vena cava thrombosis was confirmed by Doppler evaluation that revealed the presence of a complete splenoportal occlusion. Ultrasonographic assessment showed also severe hepatosplenomegaly and presence of ascites. Thrombolytic therapy with urokinase was started within 3 h from the admission. She underwent to diuretic and beta-blocking ther- apy, with gradual remission of the presenting clinical features and progressive reperfusion of the vessel. Recanalization of the portal axis was documented by ultrasound and subsequent MRI with contrast medium. Bone marrow aspiration and biopsy resulted highly suggestive for essential thrombocytemia (ET), and the cause of the clinical epiphenomena were referred to this chronic mye- loproliferative syndrome. A course of interferon-alpha, according to literature, was started and subsequent follow-ups showed a stability of clinical and laboratoristic data. Two years later, the patient was admitted again for the occurrence of ascites, subcutaneous venous collaterals and acute bleeding of oesophageal varices. She underwent to endoscopic band ligation in the emergency depart- ment. CT scan and subsequent MRI with arteriographic evaluation of splancnic arteries and veins were highly suggestive of Budd- Chiari syndrome with subsequent portal and splancnic hyperten- sion. Imaging suggested the presence of hypervascular nodules in the liver, narrowing of the vena cava and left hepatic vein occlusion. Liver biopsy showed areas of nodular hyperplasia. On- cocarbide was started, and patient was put in list for liver transplantation. Orthotopic liver transplantation was performed in November 1998, with a regular clinical course. Serial clinical and laboratoristic controls were in the normal range. In the following years patient continued her therapy with interferon-alpha. Despite her clinical history, she had two uncomplicated pregnancies after withdrawal of oncocarbide. Currently both the patient and her children are doing well. Discussion: Essential thrombocythemia (ET) is an acquired mye- loproliferative disorder with a prolonged clinical course and a near- normal life expectancy [1, 2]. It is characterized by a sustained elevation of platelet number with an increased risk for thrombosis and hemorrhage. Whereas most of the patients with ET are asymptomatic, some may experience vasomotor, thrombotic, or hemorrhagic disturbances. Arterial and venous thromboses, as well as platelet-mediated transient occlusions of the microcirculation and bleeding, represent the main risks for ET patients. This pathology has been described to complicate pregnancy with recurrent abortions, intrauterine death, and fetal growth retardation due to placental infarctions [3]. However, pregnants affected by ET have often a favourable outcome. An increased risk for thrombosis is always present among pregnants, and it can be increased in the ET subgroup. On the other hand, hemorrhagic risk is low, except in patients with acquired Von Willebrand’s disease [4]. Many pregnancies in ET have a successful outcome with minimal ther- apy. Cytoreductive treatment should preferably be avoided, especially during the first trimester [5]. Moreover, none of these has a product license for use in pregnancy. Interferon use has been associated with a higher live birth rate, whereas ASA treatment didn’t affect any major outcome [2]. IFN-a does not cross the placental barrier, and represents a potential therapeutic solution when platelet reduction is required for high risk patients. Reducing the platelet count using IFN-a might improve the chance of a successful outcome in subsequent pregnancies [5]. References 1. Birgega ̊rd G (2009) Long-term management of thrombocytosis in essential thrombocythaemia. Ann Hematol 88(1):1–10 2. Melillo L, Tieghi A, Candoni A et al (2009) Outcome of 122 pregnancies in essential thrombocythemia patients: A report from the Italian registry. Am J Hematol 84(10):636–640 3. Buyukbayrak EE, Ergen B, Karageyim Karsidag AY et al (2010) Successful pregnancy in a patient with portal hypertension secondary to portal vein thrombosis due to essential thrombocythaemia: a rare case. J Matern Fetal Neonatal Med 23(2):187–189 4. Griesshammer M, Heimpel H, Pearson T (1996) Essential thrombocythemia and pregnancy. Leuk Lymphoma 22(Suppl 1):57–63 5. Jean B Brie`re (2007) Essential thrombocythemia. Orphanet J Rare Dis 2:3. doi:10.1186/1750-1172-2-3

none 23 no Objective: To assess pregnancy and fetal outcomes after in utero exposure to interferon-beta (IFN beta) in all pregnancies occurring in women with multiple sclerosis (MS) during the study period, with a specific focus on the risk of spontaneous abortion. Methods: In this cohort study, data were gathered through a standardized, semi-structured interview. Patients who discontinued IFN beta less than 4 weeks from conception (exposed) were compared with those who had discontinued the drug at least 4 weeks from conception or who were never treated (not exposed). Possible confounders were handled through multivariate analyses adjusted for propensity score (PS). Results: We collected data on 396 pregnancies in 388 women, 88 classified as exposed (mean exposure 4.6 +/- 5.8 weeks). IFN beta exposure was not associated with an increased risk of spontaneous abortion (PS-adjusted odds ratio [OR] 1.08, 95% confidence interval [CI] 0.4 to 2.9, p = 0.88), although it was associated with both lower baby weight (PS-adjusted beta -113.8, p < 0.0001) and length (PS-adjusted beta -1.102, p < 0.0001). Proportion of spontaneous abortion in exposed patients fell within the range expected for the Italian population in the same period. IFN beta exposure (PS-adjusted OR 2.11, 95% CI 1.18 to 3.78, p = 0.012) and cesarean delivery were the only predictors of preterm delivery. In the exposed group, we did not observe any significant fetal complications, malformations, or developmental abnormalities over a median follow-up of 2.1 years. Conclusions: Our findings point to the relative safety of IFN beta exposure times of up to 4 weeks and can assist neurologists facing therapeutic decisions in women with MS with a pregnancy plan. Neurology (R) 2010;75:1794-1802 none Amato MP; Portaccio E; Ghezzi A; Hakiki B; Zipoli V; Martinelli V; Moiola L; Patti F; La Mantia L; Mancardi GL; Solaro C; Tola MR; Pozzilli C; De Giglio L; Totaro R; Lugaresi A; Di Tommaso V; Paolicelli D; Marrosu MG; Comi G; Pellegrini F; Trojano M MS Study Group of the Italian Neurological Society; De Luca G Amato MP; Portaccio E; Ghezzi A; Hakiki B; Zipoli V; Martinelli V; Moiola L; Patti F; La Mantia L; Mancardi GL; Solaro C; Tola MR; Pozzilli C; De Giglio L; Totaro R; Lugaresi A; Di Tommaso V; Paolicelli D; Marrosu MG; Comi G; Pellegrini F; Trojano M MS Study Group of the Italian Neurological Society; De Luca G

Background and aims: Evaluation of incidence and correlates of severe hypoglycemia (SH) and diabetes ketoacidosis (DKA) in children and adolescents with T1DM. Methods and results: Retrospective study conducted in 29 diabetes centers from November 2011 to April 2012. The incidence of SH and DKA episodes and their correlates were assessed through a questionnaire administered to parents of patients aged 0e18 years. Incidence rates and incident rate ratios (IRRs) were estimated through multivariate Poisson regression analysis and multilevel analysis. Overall, 2025 patients were included (age 12.4 � 3.8 years; 53% males; diabetes dura- tion 5.6 � 3.5 years; HbA1c 7.9 � 1.1%). The incidence of SH and DKA were of 7.7 and 2.4 events/ 100 py, respectively. The risk of SH was higher in females (IRR Z 1.44; 95%CI 1.04e1.99), in pa- tients using rapid acting analogues as compared to regular insulin (IRR Z 1.48; 95%CI 0.97e2.26) and lower for patients using long acting analogues as compared to NPH insulin (IRR Z 0.40; 95% CI 0.19e0.85). No correlations were found between SH and HbA1c levels. The risk of DKA was higher in patients using rapid acting analogues (IRR Z 4.25; 95%CI 1.01e17.86) and increased with insulin units needed (IRR Z 7.66; 95%CI 2.83e20.74) and HbA1c levels (IRR Z 1.63; 95% CI 1.36e1.95). Mother' sa ge was inversely associated with the risk of both SH (IRRZ 0.95; 95%CI 0.92e0.98) and DKA (IRR Z 0.94; 95%CI 0.88e0.99). When accounting for center effect, the risk of SH associated with the use of rapid acting insulin analogues was attenuated (IRR Z 1.48; 95%CI 0.97e2.26); 33% and 16% of the residual variance in SH and DKA risk was ex- plained by center effect. Conclusion: The risk of SH and DKA is mainly associated with treatment modalities and strongly depends on the practice of specialist centers.

ISBN 978-84-942844-7-2; International audience; This paper presents a parallel remeshing algorithm for distributed-memory architectures. It is an iterative parallel algorithm that divides the areas to be remeshed into multiple pieces which can be distributed to as many processing elements as pos-sible, in order for these pieces to be remeshed concurrently by a third-party sequential remesher. Then, remeshed pieces are reintegrated into the distributed mesh, and this pro-cess is iterated until all relevant areas of the mesh have been remeshed. Any sequential remesher can be used, provided it allows some of the mesh elements not to be modified, so as to preserve interfaces between pieces. Our method, which has been implemented in the PaMPA library, is validated by a set of experiments involving both isotropic and anisotropic meshes.

Purpose: We evaluated the predictors of the incidence of erectile dysfunction in patients with type 2 diabetes mellitus and identified subgroups of patients in whom the interaction between clinical and psychological characteristics determined an increase in the risk of erectile dysfunction. Materials and Methods: The study was based on 670 individuals. The presence of erectile dysfunction and the severity of depressive symptoms were investigated with a questionnaire filled in every 6 months for 3 years. Poisson regression was used to calculate incidence rates. To evaluate interactions among the different variables and identify distinct and homogeneous subgroups in terms of incidence of erectile dysfunction, RECursive Partitioning and AMalgamation method was used. Results: Overall erectile dysfunction developed in 192 men with type 2 diabetes, with an incidence rate of 166.3 per 1,000 person-years. Age, insulin treatment, hemoglobin A1c greater than 8.0%, total cholesterol greater than 3.88 mmol/l and severity of depressive symptoms represented independent predictors of erectile dysfunction. RECursive Partitioning and AMalgamation analysis identified 5 classes with a marked variation in the risk of erectile dysfunction. Patients with low levels of depressive symptoms and hemoglobin A1c 8.0% or less showed the lowest risk of erectile dysfunction. Compared with this subgroup patients with higher levels of depressive symptoms and treated with insulin had a 3-fold risk of erectile dysfunction. Age, smoking, high cholesterol levels and neuropathy were globally predictive variables associated with an increased risk of erectile dysfunction. Conclusions: The incidence of erectile dysfunction is predicted by modifiable risk factors. Even in diabetes, psychological problems can contribute to the pathogenesis of erectile dysfunction, in addition to organic causes.