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Congenital junctional ectopic tachycardia (CJET) is a rare tachyarrhythmia that remains difficult to manage, with suboptimal control in most cases. Here, we report literature research on the use of ivabradine in the treatment of pediatric junctional ectopic tachycardia (JET), both congenital and postoperative, and describe the successful use of ivabradine–flecainide association for CJET therapy resistant to other antiarrhythmic agents. This new drug combination was effective in completely suppressing JET. Ivabradine–flecainide combination may be considered a new therapeutic strategy of CJET with a satisfactory efficacy/tolerability ratio in patients resistant to conventional drug combinations.

This report presents the first case of Brugada pattern complicated by a supraventricular arrhythmia in a child with SARS-CoV-2 related Multisystem Inflammatory Syndrome in Children (MIS-C). A 7-year-old boy came to our Emergency Department with 7 days of abdominal pain and fever. MIS-C was diagnosed on the basis of the clinical, laboratory and instrumental tests. On admission, ECG showed type 1 Brugada pattern in the right precordial leads. During hospitalization the onset of supraventricular arrhythmias complicated the clinical picture. This case underlines management complexity of supraventricular arrhythmic events, different from atrial fibrillation, in patients with Brugada pattern in the context of a systemic inflammatory condition with significant cardiac involvement. All potential therapeutic choices should be considered to ensure the best outcomes.

The diagnosis of Kawasaki disease (KD) is challenging and often delayed mainly in case of young infants and in presence of an incomplete disease and atypical features. Facial nerve palsy is one of the rare neurologic symptoms of KD, associated with a higher incidence of coronary arteries lesions and may be an indicator of a more severe disease. Here, we describe a case of lower motor neuron facial nerve palsy complicating KD and perform an extensive literature review to better characterize clinical features and treatment of patients with KD-associated facial nerve palsy. The patient was diagnosed at the sixth day of disease and presented extensive coronary artery lesions. A prompt treatment with intravenous immunoglobulins, aspirin and steroids obtained a good clinical and laboratory response, with resolution of facial nerve palsy and improvement of coronary lesions. The incidence of facial nerve palsy is 0.9–1.3%; it is often unilateral, transient, more frequent on the left and seemingly associated with coronary impairment. Our literature review showed coronary artery involvement in the majority of reported cases (27/35, 77%) of KD with facial nerve palsy. Unexplained facial nerve palsy in young children with a prolonged febrile illness should prompt consideration of echocardiography to exclude KD and start the appropriate treatment.

The objective of the study is to evaluate 10 years of down-staging strategy for liver transplantation (LT) with a median follow-up of 5 years. Data on long-term results are poor and less information is available for hepatocellular carcinoma (HCC) non-responder patients or those ineligible for down-staging. The outcome of 308 HCC candidates and the long-term results of 231 LTs for HCC performed between 2003 and 2013 were analyzed. HCCs were divided according to tumor stage and response to therapy: 145 patients were T2 (metering Milan Criteria, MC), 43 were T3 successfully down-staged to T2 (Down-Achieved), 20 were T3 not fully down-staged to T2 (Down-not Achieved), and 23 patients were T3 not receiving down-staging treatments (No-Down). The average treatment effect (ATE) of LT for T3 tumors was estimated using the outcome of 535 T3 patients undergoing non-LT therapies, using inverse probability weighting regression adjustment. The 24-month drop-out rate during waiting time was significantly higher in the down-staging groups: 27.6% vs. 9.2%, p

Background: Comprehensive and contemporary data pertaining large populations of patients with Primary Biliary Cholangitis (PBC) and hepatocellular carcinoma (HCC) are missing. Aim: To describe main characteristics and outcome of PBC patients with HCC diagnosed in the new millennium. Methods: Analysing the Italian Liver Cancer registry we identified 80 PBC patients with HCC diagnosed after the year 2000, and described their clinical characteristics, access to treatment and survival. Results: Median age of patients was 71 years and 50.0% were males. Cirrhosis was present in 86.3% of patients, being well-compensated in 58.0%. Median HCC diameter was smaller in patients under surveillance (2.6vs 4.0cm, P=0.007). Curative treatment, feasible in 50.0% of patients, was associated with improved survival compared to palliative and supportive care (42vs 33vs 6 months, P

Background An enhanced surveillance schedule has been proposed for cirrhotics with viral etiology, who are considered at extremely high-risk of hepatocellular carcinoma (HCC). Aims We compared the 3- and 6-months surveillance interval, evaluating cancer stage at diagnosis and patient survival. Methods Data of 777 HBV and HCV cirrhotic patients with HCC diagnosed under a 3-months (n = 109, 3MS group) or a 6-months (n = 668, 6MS group) surveillance were retrieved from the Italian Liver Cancer database. Survival in the 3MS group was considered as observed and adjusted for lead-time bias, and survival analysis was repeated after a propensity score matching. Results The 3-months surveillance interval neither reduced the share of patients diagnosed outside the Milano criteria, nor increased their probability to receive curative treatments. The median survival of 6MS patients (55.0 months [45.9–64.0]) was not significantly different from the observed (47.0 months [35.0–58.9]; p = 0.43) and adjusted (44.9 months [33.4–56.4]; p = 0.30) survival of 3MS patients. A propensity score analysis confirmed the absence of a survival advantage for 3MS patients. Conclusions A tightening of surveillance schedule does not increase the diagnosis of early-stage tumors, the feasibility of curative treatments and the survival. Therefore, we should maintain the 6-months interval in the surveillance of viral cirrhotics.

Background: Hepatocellular carcinoma prognosis depends on both liver and tumor determinants, especially on maximum tumor diameter, multifocality, and presence of portal vein thrombosis, despite apparently complete tumor removal by resection or liver transplantation. Aims: To examine parameters of hepatocellular carcinoma aggressiveness as tumor size increases. Methods: A large hepatocellular carcinoma database was examined for trends in serum alpha-fetoprotein and the percentage of patients with macroscopic portal vein thrombosis or tumor multifocality. Results: A total of 13,016 hepatocellular carcinoma patients were identified having full tumor and survival data. Of these, 76.56% were male and 23.44% were female, with a median age of 64.4 years. We found that as the maximum tumor diameter increased, there was a significant trend for increased alpha-fetoprotein levels ( PConclusions: The greater fold-increases in alpha-fetoprotein and portal vein thrombosis compared with increases in maximum tumor diameter imply that hepatocellular carcinoma characteristics may change with increasing size to a more aggressive phenotype, suggesting that follow-up tumor sampling might be useful, in addition to baseline tumor sampling, for optimal therapeutic choices to be made.

Background. Hepatocellular carcinoma (HCC) factors, especially maximum tumor diameter (MTD), tumor multifocality, portal vein thrombosis (PVT), and serum alpha-fetoprotein (AFP), influence survival. Aim. To examine patterns of tumor factors in large HCC patients. Methods. A database of large HCC patients was examined. Results. A multiple Cox proportional hazard model on death identified low serum albumin levels and the presence of PVT and multifocality, with each having a hazard ratio ≥2.0. All combinations of these three parameters were examined in relation to survival. Using univariate Cox analysis, the combination of albumin &gt, 3.5 g/dL and the absence of both PVT and multifocality had the best survival rate, while all combinations that included the presence of PVT had poor survival and hazard ratios. We identified four clinical phenotypes, each with a distinct median survival: patients with or without PVT or multifocality plus serum albumin ≥3.5 (g/dL), with each subgroup displaying high (≥100 IU/mL) or low (&lt, 100 IU/mL) blood AFP levels. Across a range of MTDs, we identified only two significant trends, blood AFP and platelets. Conclusions. Patients with large HCCs have distinct phenotypes and survival, as identified by the combination of PVT, multifocality, and blood albumin levels.

Introduction: The prognosis of patients undergoing transarterial chemoembolization (TACE) is extremely variable, and a confounding factor is that TACE is often repeated several times. We retrospectively evaluated the accuracy of different prognostic scores and staging systems in estimating overall survival (OS) in patients with hepatocellular carcinoma (HCC). Methods: An analysis considering prognostic models as time-varying variables was performed, calculating OS from the time of TACE to the time of the subsequent treatment. Total follow-up time for each patient was therefore split into several observation times accounting for each TACE procedure. Values of the likelihood ratio test (LRT) and Akaike information criterion (AIC) were used to compare different systems. Univariable and multivariable analyses were conducted to identify additional factors predictive of OS. We analyzed 1,610 TACE performed in 1,058 patients recorded in the Italian Liver Cancer database from 2008 through 2016. Results: The median OS of the enrolled patients was 41 months. According to LRT χ2 and AIC values based on the time-varying analysis, mHAP-III achieved the best values (41.72 and 4,625.49, respectively, p < 0.0001), indicating the highest predictive performance compared with all other scores (HAP, mHAP-II, ALBI, and pALBI) and staging systems (MELD, ITALICA, CLIP, MESH, MESIAH, JIS, HKLC, and BCLC). In the multivariable Cox proportional hazards model, mHAP-III maintained an independent effect on OS (hazard ratio 1.31, 95% CI: 1.10–1.55, p < 0.0001). Time-varying age, alcoholic etiology, radiologic response to TACE, and performing ablation or surgery after TACE were additional significant variables resulting from the multivariable model. Conclusion: An innovative time-varying analysis revealed that mHAP-III was the most accurate model in predicting OS in patients with HCC undergoing TACE. Other clinical pre- and post-TACE variables were also found to be relevant for this prediction.

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits and collated via case report forms. Results: In total, 956 patients with CTEPH were included in the analysis. The most common AEs in these patients were peripheral edema/edema (11.7%), dizziness (7.5%), right ventricular (RV)/cardiac failure (7.7%), and pneumonia (5.0%). The most common SAEs were RV/cardiac failure (7.4%), pneumonia (4.1%), dyspnea (3.6%), and syncope (2.5%). Exposure-adjusted rates of hemoptysis/pulmonary hemorrhage and hypotension were low and comparable to those in the long-term extension study of riociguat (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial [CHEST-2]). Conclusion: Data from EXPERT show that in patients with CTEPH, the safety of riociguat in routine practice was consistent with the known safety profile of the drug, and no new safety concerns were identified. © 2020 The Authors Eli Lilly and Company; Pfizer; Bayer; GlaxoSmithKline; Merck; Actelion Pharmaceuticals; Meso Scale Diagnostics; United Therapeutics Corporation; Novartis Pharma; Merck Sharp and Dohme; GlaxoSmithKline Australia; Deutsche Forschungsgemeinschaft; Grupo Ferrer Internacional, S.A The EXPERT registry was funded by Bayer AG (Berlin, Germany) and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA. The authors acknowledge the database administration by Torsten Tille, Dresden, and the project administration of Mrs Romy Hoppenz and Mrs Linda Kottke at GWT-TUD GmbH, Dresden. Medical writing services provided by Richard Murphy PhD of Adelphi Communications Ltd, Macclesfield, UK were funded by Bayer AG in accordance with Good Publication Practice (GPP3) guidelines. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof Marius M. Hoeper reports personal fees from Bayer AG, during the conduct of the study; personal fees from Actelion, personal fees from Acceleron, personal fees from MSD, personal fees from Jansen, personal fees from Pfizer, outside the submitted work. Dr Hans Klose reports speaker and consultancy fees from Actelion, Bayer AG, GSK, Novartis, Pfizer, and United Therapeutics and research support from Actelion, Bayer AG, GSK, Pfizer, and MSD. Dr Michael Halank reports personal fees and non-financial support from Actelion, AstraZeneca, Bayer AG, Berlin-Chemie, GSK, OMT, MSD, and Novartis. Dr George Giannakoulas reports speaker and consultancy fees from Actelion, Bayer, ELPEN Pharmaceuticals, GSK, Pfizer, Lilly, and United Therapeutics, and research support from GSK, ELPEN Pharmaceuticals, and Galenica. Dr Henning Gall has received honoraria and/or other support from Actelion, AstraZeneca, Bayer, BMS, GSK, Janssen-Cilag, Lilly, MSD, Novartis, OMT, Pfizer, and United Therapeutics. Dr Pavel Jansa reports consultancy and speaker fees from MSD, AOP Orphan, and Actelion. Prof Ekkehard Grünig reports research grants and speaker honoraria/consultancy fees from Actelion and Bayer/MSD, research grants from GSK, United Therapeutics, Bellerophon, OMT GmbH, Pfizer, Reata, and Novartis, and speaker honoraria from Bial, Medscape, and OrPha Swiss GmbH. Prof David Pittrow reports personal fees from Actelion, Bayer AG, Aspen, Boehringer Ingelheim, Sanofi, Biogen, Shire, and MSD outside the submitted work. Silvia Ulrich reports research grants and personal fees from Actelion, Bayer, MSD, and Orpha Swiss. Tobias J. Lange has received personal fees from Actelion, MSD, Pfizer, and OMT orphan. Dr Iraklis Tsangaris reports speaker and consultancy fees from Actelion, Bayer AG, ELPEN, GSK, MSD, Pfizer, and United Therapeutics. Stephan Rosenkranz reports remunerations for lectures and/or consultancy from Abbott, Actelion, Arena, Bayer, Ferrer, GSK, MSD, Novartis, Pfizer, and United Therapeutics; and research support to his institution from Actelion, Bayer, Novartis, Pfizer, and United Therapeutics. Repke J. Snijder reports grants from Pfizer and Actelion Pharmaceuticals. Prof Iveta Šimková reports consultancy and speaker fees from MSD, AOP Orphan, and Actelion. Dr Marc Humbert reports grants and personal fees from Bayer and GSK, and personal fees from Actelion, Merck, and United Therapeutics. Marion Delcroix has received investigator, speaker, consultant, and steering committee member fees from Actelion, Bayer AG, Bellerophon, Eli Lilly, GlaxoSmithKline, MSD, Pfizer, and Reata, and research grants from Actelion. Joan A. Barberà reports receipt of honoraria for consultation or speaker fees from Actelion and Merck; and research support through his institution from Actelion, Merck, GlaxoSmithKline, and Ferrer. Joanna Pepke-Zaba reports research grants and speaker honoraria/consultancy fees from Actelion, Bayer/MSD, and GSK. Jean-Luc Vachiéry reports ongoing consultancies to Actelion, Sonnivie, Arena Pharma, Bial Portela, and Respira Therapeutics, past consultancies to AstraZeneca, BayerShering, CardioMEMS, GlaxoSmithKline, Pfizer, Merck, and United Therapeutics, and current membership of an advisory board or similar group for Actelion and GlaxoSmithKline. Jean-Luc Vachiéry's institution receives funding from Actelion Pharmaceuticals for performing clinical studies. Regina Steringer-Mascherbauer, Jens Klotsche, and Miguel-Angel Gomez Sanchez have no conflicts of interest relevant to the EXPERT study. Hossein-Ardeschir Ghofrani reports personal fees for advisory board work, and payment for lectures including service on speaker bureaus, from Actelion, Bayer, GSK, Novartis, and Pfizer; consultancy fees from Actelion, Bayer, Bellerophon Pulse Technologies, GSK, MSD, Novartis, and Pfizer; and grants from Deutsche Forschungsgemeinschaft (DFG). Pilar Escribano Subias reports personal fees from Actelion, Bayer AG, GlaxoSmithKline, and Merck Sharp & Dohme, and grants from Actelion, Bayer AG, GlaxoSmithKline, and Ferrer, outside the submitted work. Gérald Simonneau reports personal fees and non-financial support from Actelion, personal fees and non-financial support from Bayer, personal fees and non-financial support from MSD, outside the submitted work. Douglas S. Helmersen reports industry-sponsored research with Bayer AG, United Therapeutics, and Gilead Sciences, Inc., and advisory board/speaker fees from Bayer AG and Actelion. David Langleben reports honoraria, consultation fees, research support, and/or travel expenses from Actelion, Arena, Bayer AG, Northern Therapeutics, PhaseBio, Acceleron, Janssen, and United Therapeutics. Anco Boonstra reports consultancy fees from Pfizer BV and hospitality from Teva Nederland. Lisa M. Mielniczuk reports speaker fees and honoraria from Bayer AG, and speaker fees, consultancy fees, and travel fees from Actelion. Evgenia Williams and Christian Meier are employees of Bayer AG.

The etiologic diagnosis of pulmonary hypertension (PH) may be very challenging. Right-heart catheterization (RHC) in isolation cannot classify a precapillary PH patient into group 1, 3, 4, or 5. Moreover, RHC may be not sufficient for reaching a definitive differential diagnosis of precapillary or postcapillary PH if hemodynamic data are not integrated in clinical context and combined with information gleaned from noninvasive imaging. Therefore, only the integration of risk factors, clinical evaluation, invasive and noninvasive tests allows the physician to distinguish between different forms of PH.

Background: The Italian Liver Cancer (ITA.LI.CA) prognostic system for patients with hepatocellular carcinoma (HCC) has recently been proposed and validated. We sought to explore the relationship among the ITA.LI.CA prognostic variables (ie tumour stage, functional score based on performance status and Child-Pugh score, and alpha-fetoprotein), treatment selection and survival outcome in HCC patients. Patients and Methods: We analysed 4,867 consecutive HCC patients undergoing six main treatment strategies (liver transplantation, LT; liver resection, LR; ablation, ABL; intra-arterial therapy, IAT; Sorafenib, SOR; and best supportive care, BSC) and enrolled during 2002-2015 in a multicenter Italian database. In order to control pretreatment imbalances in observed variables, a machine learning methodology was used and inverse probability of treatment weights (IPTW) was calculated. An IPTW-adjusted multivariate survival model that included ITA.LI.CA prognostic variables, treatment period and treatment strategy was then developed. The survival benefit of HCC treatments was described as a hazard ratio (95% confidence interval), using BSC as a reference value and as predicted median survival. Results: After the IPTW, the six treatment groups became well balanced for most baseline characteristics. In the IPTW-adjusted multivariate survival model, treatment strategy was found to be the strongest survival predictor, irrespective of ITA.LI.CA prognostic variables and treatment period. The survival benefit of different therapies over BSC was: LT=0.19 (0.18-0.20); RES=0.40 (0.37-0.42); ABL 0.42 (0.40-0.44); IAT=0.58 (0.55-0.61); SOR=0.92 (0.87-0.97). This multivariate model was then used to predict median survival for each therapy within each ITA.LI.CA stage. Conclusion: The concept of therapeutic hierarchy was established within each ITA.LI.CA stage.

Background and Aims:Hepatocellular carcinoma is associated with several chronic liver diseases, especially chronic hepatitis B virus, hepatitis C virus, and alcoholism. It is increasingly appreciated that obesity/metabolic syndrome is also associated with chronic liver disease and subsequent hepatocellular carcinoma.Methods:We retrospectively investigated the serum lipid profiles in a large hepatocellular carcinoma cohort, associated predominantly with the hepatitis B virus, hepatitis C virus, alcohol or nonalcoholic steatohepatitis. The cohort was examined both as a whole, as well as stratified by etiology.Results:We found significant associations between parameters of hepatocellular carcinoma biology such as maximum tumor diameter, portal vein thrombosis, tumor multifocality or alpha-fetoprotein levels and individual lipid components, including total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides and body mass index. In a final multiple linear regression model considering all lipid variables together, only high-density lipoprotein cholesterol was significantly associated with the tumor Tumor Aggressiveness Index. High-density lipoprotein cholesterol was found to have a statistically higher hazard ratio for death than low high-density lipoprotein cholesterol levels (Cox). On examination by etiological group, alpha-fetoprotein levels were significantly higher in patients with hepatitis C virus compared to those with alcohol or nonalcoholic steatohepatitis, but maximum tumor diameter, tumor multifocality and portal vein thrombosis were similar across etiological groups. Nonalcoholic steatohepatitis patients had significantly less cirrhosis than other groups and hepatitis B virus patients had significantly higher cholesterol and low-density lipoprotein cholesterol levels than hepatitis C virus patients.Conclusions:This is the first report, to our knowledge, of a relationship between serum lipid parameters and indices of hepatocellular carcinoma growth, invasion and aggressiveness, as well as with survival.

The etiologic diagnosis of pulmonary hypertension (PH) may be very challenging. Right-heart catheterization (RHC) in isolation cannot classify a precapillary PH patient into group 1, 3, 4, or 5. Moreover, RHC may be not sufficient for reaching a definitive differential diagnosis of precapillary or postcapillary PH if hemodynamic data are not integrated in clinical context and combined with information gleaned from noninvasive imaging. Therefore, only the integration of risk factors, clinical evaluation, invasive and noninvasive tests allows the physician to distinguish between different forms of PH.

Two studies were conducted during the Italian General Elections of 2006 (N = 179) and 2008 (N = 607), to investigate the relationships among implicit and explicit attitudes, voting intention and voting behaviour. Several structural equation models that included direct and indirect effect of implicit and explicit attitudes toward political objects (coalitions and leaders) on voting intention and behaviour were executed to test a prediction model of political preferences and voting behaviour. Notwithstanding some differences, the results of the two studies showed that (i) the implicit evaluations of political objects are more differentiated than the explicit ones; (ii) that implicit attitudes contribute in a specific and additive way to determine the voting intention and behaviour, and (iii) that the effect of the implicit attitude is also mediated by the explicit attitudes. Findings are discussed in the frame of dual cognition models and in the light of the peculiar political scenarios of the considered electoral process.

Aim: A fluid challenge with rapid saline infusion during right heart catheterization has been shown to be useful for the differential diagnosis between pre- and post-capillary pulmonary hypertension. The aim of this study was to evaluate the prognostic relevance of fluid challenge-induced changes in pulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH).Methods: Overall, 118 PAH patients (mean age 57 +/- 15 years, 80 female) underwent hemodynamic measurements before and after rapid saline infusion (7 mL/kg in 10 min) and were followed up for 19 +/- 4 months.Results: Thirty-two patients (27%) had a clinical worsening event defined as the occurrence of one of the following: death, lung transplantation, initiation of parenteral prostanoids, or worsening of PAH (defined as the presence of all of the three following components: a decrease in the 6-minute walk distance of at least 15% from baseline, worsening of PAH symptoms, and need for new PAH treatment). Cardiac index (CI), stroke volume and pulmonary artery compliance were lower whereas right atrial pressure (RAP), the ratio of RAP to pulmonary artery wedge pressure (PAWP) and pulmonary vascular resistance were higher in patients with a clinical worsening event versus patients without events, both at baseline and after fluid challenge (all p < 0.01). At multivariable Cox proportional hazards regression analysis, a post-fluid challenge CI

Aim: To determine whether right atrial (RA) function has prognostic value in patients with idiopathic pulmonary arterial hypertension (PAH).Methods and results: Overall, 104 patients (70 female, mean age 58 +/- 13 years) with idiopathic PAH underwent standard Doppler echocardiography and strain and strain rate (SR) analysis before right heart catheterization. At a mean follow-up of 22 +/- 7 months, 30 patients (29%) had clinical worsening. On Cox multivariable proportional-hazards regression analysis, RA reservoir function measured as peak longitudinal SR (hazard ratio [HR] 0.5; P < 0.0001), RA area (HR 1.2; P < 0.01), right ventricular (RV) SR (HR 0.6; P < 0.0001), cardiac index (HR 0.79; P < 0.01), and mixed venous oxygen saturation (HR 0.82; P < 0.01) were found to be independent correlates of cardiac events. A RA SR reservoir cut-off value of

AIMS A simple echocardiographic score was designed for diagnosing precapillary vs postcapillary pulmonary hypertension and for discriminating between isolated postcapillary pulmonary hypertension (Ipc-PH) and combined precapillary and postcapillary pulmonary hypertension (Cpc-PH). METHODS The score comprised 7 points (2 for E/e' ratio ≤10, 2 for a dilated non-collapsible inferior vena cava, 1 for a left ventricular eccentricity index ≥1.2, 1 for a right-to-left heart chamber dimension ratio >1 and 1 for the right ventricle forming the heart apex) and was applied to 230 consecutive patients referred for evaluation of pulmonary hypertension. RESULTS Precapillary pulmonary hypertension and postcapillary pulmonary hypertension were diagnosed in 160 and 70 patients, respectively. In the latter, Ipc-PH was found in 51 and Cpc-PH in 19. The echo score was higher in precapillary vs postcapillary pulmonary hypertension patients (4.2 ± 1.7 vs 1.6 ± 1.7, P

Down syndrome (DS) is the most common autosomal chromosome abnormality with an estimated incidence of approximately 1.1 per 1000 live births, without significant differences across different races. Pulmonary hypertension (PH) can significantly affect the prognosis and quality of life of DS patients. While the most common cause of PH is congenital heart disease (CHD), DS is often associated with comorbidities that may cause or worsen PH.

Background Fluid challenge may help in the differential diagnosis between pre- and postcapillary pulmonary hypertension (PH). However, the test is still in need of standardization and better defined clinical relevance. Methods Two hundred twelve patients referred for PH underwent a right-sided heart catheterization with measurements before and after rapid infusion of 7mL/kg of saline. PH was defined as mean pulmonary artery pressure≥ 25mmHg, and postcapillary PH was defined as pulmonary artery wedge pressure (PAWP) > 15mmHg. An increase in PAWP≥ 18mmHg was considered diagnostic for postcapillary PH. At baseline, 66 patients received a diagnosis of no PH; 22, of postcapillary PH; and 124, of precapillary PH (mostly pulmonary arterial hypertension). Results After fluid challenge, five of 66 patients with no PH (8%) and eight of 124 with precapillary PH (6%) had the diagnosis reclassified as postcapillary PH. Fluid challenge was associated with an increase in PAWP by 7 ± 2mmHg in postcapillary PH and 3 ± 1mmHg in both precapillary PH and no-PH groups. Between-group differences were significant, but there was overlap. There were no adverse events related to fluid challenge. Prediction bands calculated from quadratic fits of the PAWP responses in pooled control subjects with no PH and patients with precapillary PH helped confirm 18mmHg as the cutoff for diagnosing postcapillary PH. Conclusions Fluid challenge with 7mL/kg saline increases PAWP, more in postcapillary than in precapillary PH or in control subjects with no PH. A cutoff value of 18mmHg allows reclassification of 6%to 8%of patients with precapillary PH or normal hemodynamic characteristics at baseline.

Background: Exercise-induced increase in pulmonary artery systolic pressure (PASP) as a possible measure of right ventricular (RV) contractile reserve has been shown to predict survival in severe pulmonary hypertension. However, RV contractile reserve can also be measured by changes in stroke volume (SV), tricuspid annular plane systolic excursion (TAPSE), or tricuspid annular systolic velocity (S'). The limits of normal values and the functional significance of these changes in healthy subjects are not well known. Methods: In this prospective study, 90 healthy subjects (45 male, mean age 39 ± 13years) underwent exercise stress echocardiography with measurement of TAPSE, S', TAPSE/PASP, SV, and PASP at rest and peak exercise. Maximum and minimum normal values were reported for all indices. Results: Normal values of exercise-induced changes (Δ) were 4 to 10mm for TAPSE, 6 to 14cm/s for S', 12 to 57mm Hg for PASP, 0 to 96mL for SV, and −1.2 to 0mm/mm Hg for TAPSE/PASP. At peak exercise, women showed lower ΔTAPSE/PASP, ΔPASP, ΔS', and ΔSV, but higher TAPSE/PASP than men. Aging was associated with decreased ΔTAPSE/PASP, ΔTAPSE, ΔS', ΔPASP, and ΔSV. In addition, ΔS', ΔTAPSE/PASP, ΔPASP, and ΔSV, but not ΔTAPSE, were directly correlated with maximum workload. Conclusions: Our results provide age- and sex-related limits of normal for RV contractile reserve as assessed by exercise stress echocardiography and demonstrate that RV systolic function indices (PASP, TAPSE, S', and TAPSE/PASP) correlate with maximum exercise capacity.

Background: Echocardiography is a valid tool for predicting the presence of pre- or post-capillary pulmonary hypertension (PH). A diastolic pulmonary gradient (DPG) equal or higher than 7 mmHg is a marker of pulmonary vascular disease also in patients with post-capillary PH. Aim: To detect if an echocardiographic score is able to allow a differential diagnosis between isolated post-capillary PH (Ipc-PH) and combined post- and pre-capillary PH (Cpc-PH). Methods: An echo-score, including right-to-left-heart chamber dimension >1 (2 points), dilation and no collapsibility of inferior vena cava (2 points), left ventricular eccentricity index ≥1.2 (1 point), E/e9 ratio ≤10 (1 point), and the right ventricle forming the heart apex (1 point), was applied to 230 consecutive patients referred for evaluation of PH and quasi-simultaneous right heart catheterization RHC (within 1 hour). Results: One-hundred-sixty/230 (70%) patients had pre-capillary PH and 70/230 (30%) had post-capillary PH. Within the 70 patients with post-capillary PH, 51/70 had Ipc-PH and 19/70 had Cpc-PH. There was a moderate linear correlation between Echo score and DPG (R 2 = 0.34). Echo score was higher in pre- vs post-capillary PH patients (4.0±2.0 vs 1.6±1.8, p The sensitivity and the specificity of Echo score ≥3 for pre-capillary PH were respectively 74% and 73%. Considering the 70 patients with post-capillary PH, the sensitivity and the specificity of Echo score ≥3 for Cpc-PH were respectively 68% and 88%. Conclusions: Echocardiography allows a satisfactory differential diagnosis not only between pre- and post-capillary PH, but also between Ipc-PH and Cpc-PH.

Objectives: Undifferentiated connective tissue disease at risk for Systemic Sclerosis (UCTD-risk-SSc) is a condition characterized by Raynaud9s phenomenon (RP) with SSc marker autoantibodies and/or typical capillaroscopic findings and unsatisfying classification criteria for the disease. UCTD-risk- SSc patients have been reported to show a preclinical vascular internal organ disease in about 40% of the patients. The present study is devoted to assess the prevalence of right (RV) or left ventricle (LV) systolic and/or diastolic dysfunction as assessed by tissue Doppler imaging (TDI). Methods: Fifty-three patients with UCTD-risk-SSc (46 female, aged 45±12 years, range 16-67) and 52 age- and sex-matched controls underwent cardiac assessment by standard echocardiography and TDI. Results: UCTD-risk-SSc patients and controls did not show any difference at standard echocardiographic evaluation. In particular, an inverted E/A ratio was pointed out in 14/53 patients and 12/52 controls (p=ns). TDI showed a mild impairment of LV and RV diastolic (E m 16±5 vs 19±5, p m 6.3±3.0 vs 4.9±1.4, p=0.005; E t 16±4 vs 18±3, p=0.03; E t /A t 1.1±0.4 vs 1.3±0.4, p m 11±3 vs 14±2 cm/sec, p t 14±3 vs 16±3 cm/sec, p=0.01) in UCTD- risk-SSc patients in comparison to controls. Estimated pulmonary artery systolic pressure (27±5 vs 25±4; p=0.07) and TAPSE (23±3 vs 23±4; p=0.20) were not significantly different between the 2 groups. Conclusions: Our study shows that UCTD-risk-SSc patients present a previously unrecognized, mild biventricular systolic and diastolic dysfunction as compared to controls.

Aim: To explore the hemodynamic response to a fluid challenge test (FCT) in normal subjects and in patients with different forms of pulmonary hypertension (PH). Methods: Two-hundred-twentysubjects underwent right heart catheterization in basal conditions and after FCT (volume loading with rapid saline infusion of 7 mL/Kg in 10 min). Results: At baseline, 61 subjects showed normal pressures (healthy controls), 22 post-capillary, 118 different forms of pre-capillary PH (mainly pulmonary arterial hypertension - PAH) and 11 patients, 5 apparently normal and 6 considered having PAH at baseline, were considered patients with “hidden post-capillary PH” after FCT due to a steeper increase in pulmonary arterial wedge pressure (PAWP, >7 mmHg increase reaching an absolute value >20 mmHg). All measurements were obtained at baseline and immediately after FCT. Rapid volume loading resulted in a significant increase in right atrial pressure (RAP), PAWP, mean pulmonary arterial pressure (mPAP) and cardiac index (CI) in all groups. RAP and mPAP increased more in pre- and post-capillary PH than in controls (respectively: 5±2 and 5±2 vs 3±2 mmHg, both p Conclusions: Pulmonary pressures rise significantly with volume loading, even in healthy volunteers. The response in acute volume loading is different in pre- and post-capillary PH patients.

Background: Right ventricular (RV) contractile reserve measured as exercise-induced increase in the pulmonary artery systolic pressure (PASP) has been shown to predict survival in severe pulmonary hypertension. However, RV contractile reserve can also be measured by changes in stroke volume (SV), tricuspid annular plane excursion (TAPSE) or tricuspid annulus systolic velocity (S). Aim: To explore the limits of normal and functional significance of these changes in healthy subjects, that is not exactly known so far. Methods and results: We measured PASP, TAPSE, SV, and S in 90 subjects aged 39 ± 13 yrs, 50% female, at rest and at maximum exercise, and estimated limits of normal as mean – 2SD to mean + 2SD. Normal values of exercise-induced changes (Δ) were 4 to 10 mm for TAPSE, 6 to 14 cm/s for S, 0 to 96 ml for SV, 12 to 57 mmHg for PASP and – 1.2 to 0 mm/mmHg for TAPSE/PASP. Limits of normal (shaded) and exercise-induced changes as a function of workload in TAPSE, S, SV, and PASP are shown in Figure 1. As compared to men (n=45), women had decreased ΔS, ΔTAPSE/PASP, ΔPASP and ΔSV, but increased TAPSE/PASP at peak exercise. Aging was associated with decreased ΔS, ΔTAPSE, ΔPASP, ΔSV and TAPSE/PASP. Changes in S, TAPSE/PASP, PASP and SV were directly correlated to workload. Conclusions: These results provide age- and sex-related limits of normal RV contractile reserve as assessed by stress echocardiographic PASP, TAPSE, S and TAPSE/PASP. Right ventricular contractile reserve, however measured, correlates with exercise capacity.

Four HCC characteristics typically inform tumor behavior: maximum tumor size, number of nodules, portal vein thrombosis and serum AFP level. The sum of these parameters was recently published as an HCC Aggressiveness Index. We aimed to validate this index retrospectively in a larger and independent HCC cohort of 2706 Italian HCC patients, and to evaluate a possible relationship between the index and liver function parameters. The scores in the HCC Aggressiveness Index were again found to significantly relate to patient survival. Furthermore, in a multiple logistic regression model of the Aggressiveness Index score categories, there were significant differences in several liver parameter terciles amongst the score categories, suggesting a relationship of liver function to tumor aggressiveness. It was concluded that a prognostically significant Tumor Aggressiveness Index was validated and was found to be related to levels of some common liver function parameters.

Enlargement and dysfunction of the right atrium might be an early sign for pulmonary hypertension in systemic sclerosis (SSc). This is the first study to analyse right atrial morphology and function in SSc patients compared to healthy controls by speckle-tracking two-dimensional strain echocardiography (2DSE) at rest and during exercise. Furthermore, right atrial function was correlated with further clinical findings. Adult patients with SSc for > 3 years (n = 90) and 55 age- and gender-matched healthy controls underwent a panel of non-invasive assessments including transthoracic echocardiography, pulsed Doppler myocardial imaging and 2DSE at rest and during exercise. Furthermore, serological tests and high-resolution chest computed tomography were performed. SSc patients showed significant impairment of right atrial function and the right atrial enlargement, measured by 2DSE at rest and during exercise compared to controls (both p < 0.001). These findings were more evident in SSc patients with pulmonary fibrosis (p < 0.001) and in patients with high pulmonary artery systolic pressures (PAPs) during exercise. In the SSC patients, right atrial lateral strain was significantly associated with PAPs during effort, right atrial area, left ventricle stroke volume and inferior vena cava diameter using multivariable analysis. The findings of this study suggest that a high proportion of SSc patients reveal right atrial dysfunction even without manifest pulmonary hypertension. Impaired right atrial function occurred mostly in patients with pulmonary fibrosis and/or elevated PAPs during exercise, was independently associated with prognostic factors and may therefore be useful for risk stratification. Further studies are needed to analyse if right atrial dysfunction assessed by 2DSE may help to improve early diagnosis of pulmonary hypertension.

A Hepatocellular (HCC) Aggressiveness Index was recently constructed, consisting of the sum of the scores for the 4 clinical parameters of maximum tumor size, multifocality, presence of portal vein thrombus and blood alphafetoprotein levels. It was observed that there was an association with several liver function tests. We have now formed a Liver Index from the 4 liver parameters with the highest hazard ratios with respect to HCC aggressiveness, namely: blood total bilirubin, gamma glutamyl transpeptidase (GGTP), albumin and platelet levels (cirrhosis surrogate). We found that the scores for the Liver Index related significantly to survival, but also to the Aggressiveness Index and to its individual HCC components as well as showing significant trends with the components. These results support the hypothesis that liver function is not only an important prognostic factor in HCC patients, but may also be involved in HCC biology and aggressiveness. Blood albumin, GGTP, albumin and platelet levels were used to create a Liver Index that related significantly to parameters of HCC aggressiveness.

Aims Relationship between obesity and cardiovascular (CV) disease depends not only on the amount of body fat, but also on its distribution. For example, individuals with increased fat accumulation in the abdominal region have atherogenic lipid profiles and are at increased CV risk. The loss of elasticity in medium and large arteries is an early manifestation of atherosclerosis. The aim of this study was to evaluate whether echocardiographic epicardial adipose tissue, an index of cardiac adiposity, is related to carotid stiffness and carotid intima-media thickness (IMT), indexes of subclinical atherosclerosis, better than waist circumference in hypertensive patients.Methods and results We studied 459 patients with Grade I and II essential hypertension who were referred to our outpatient clinic over a period from May 2007 to March 2008. The population was first sorted by waist circumference and then by epicardial fat ≤7 or >7 mm. We measured epicardial fat thickness, waist circumference, carotid artery stiffness, and carotid IMT in all patients. Patients divided according to waist circumference showed no statistical differences in carotid artery stiffness between the two groups. Subjects with epicardial fat >7 mm were older, had higher systolic, diastolic, and pulse pressure, increased left ventricular mass index, carotid IMT, diastolic parameters, and stiffness parameters compared with those with epicardial fat ≤7 mm (P < 0.001). A positive correlation was found between epicardial fat and age, pulse pressure, stiffness parameters, carotid IMT, systolic blood pressure, and duration of hypertension, and a negative correlation was found with diastolic parameters. Age, carotid IMT, and stiffness parameters were independently related to epicardial fat.Conclusion Our findings indicate that epicardial fat reflects carotid artery stiffness in hypertension-induced organ damage. © The Author 2009.

To evaluate differences in success rate between two dosages of intraluminal urokinase (IL-UK) for treatment of withdraw occlusion in central venous catheters (CVC) and to confirm the efficacy of a salvage protocol with low-dose systemic urokinase (S-UK) in case of failure of IL-UK or of complete catheter obstruction.All malfunctioning or occluded partially implanted indwelling catheters inserted in a 29-month period in children with cancer at two tertiary care centers (Genoa and Turin) in Italy were eligible for this study. In cases of withdraw occlusion, IL-UK was used as first-line treatment with different schedules of administration in the two centers: a 5,000 IU/ml dose was used in Genoa and a 25,000 IU/ml dose in Turin (Protocol A). In case of failure of the front-line protocol or in case of complete CVC occlusion, S-UK at 1,000 IU/kg per hour for 3 h was used as a salvage protocol in both centers (Protocol B).There were 81 episodes of malfunction and three of occlusion recorded in 68 CVCs. Protocol A was successful in 75 (92.5%) of the malfunction episodes. In particular, the dose of 5,000 IU of IL-UK was successful in 42 (89%) CVCs while the 25,000 IU dose resolved 33 (97%) of the episodes (not significant). The six patients with CVC refractory to IL-UK and the three subjects with complete CVC occlusion were treated with S-UK. Patency was obtained in seven cases (78%); the remaining two catheters had to be removed.We found that 5,000 IU of IL-UK were as effective as 25,000 IU to resolve withdrawal occlusion in partially implanted CVCs and that systemic treatment with urokinase may rescue a significant proportion of CVCs refractory to IL-UK or that are apparently completely occluded.

e13052 Background: Obesity prevalence among Hispanic communities is alarmingly high. The correlation between obesity and elevated blood glucose levels with increased cancer risk has remained controversial for several years. Thus, the main objectives of this study are: 1) to estimate the prevalence of obesity and overweight in a women cancer population; 2) to compare our findings with the general population; 3) to assess the stage at time of diagnosis by cancer site. Methods: An exploratory, cross-sectional study was conducted at one oncology women clinic located in Ponce, Puerto Rico. The medial records were selected by a Simple Random Sampling, all adult women with any type of cancer were included. Descriptive statistics were used to summarize patient demographics, morbidity, and clinical characteristics. Results: 216 medical records were reviewed. The distribution by age group was: 21-30 (n = 3 (1.4%); 31-35 (n = 35 (16.2%); 46-64 (n = 96(44.4%); ≥65 (n = 82(38%). The 50.5% (109) of the patients presented breast cancer, 24 (11.2%) uterine cancer and 17 (7.9%) colon cancer. FBS ≥ 126 was presented by 38 participants (19.6%). A BMI ≥ 30 was presented by 121 (56%) of the patients and 54 (25%) were overweight (81% of obesity and overweight). Obesity and overweight in women from Puerto Rico Behavioral Risk Surveillance System (PRBRFSS, 2014) presents a prevalence of 64% and Loren et al (2014) found a prevalence of 65.1% in women without cancer, comparing with our finding (81%) this difference is statistically significant (p < 0.05). A 26.9% (n = 58) of Hispanic women in our study presented diabetes vs 17.2% in the Hispanic women population (PRBRFSS, 2015) this difference is statistically significant (p < 0.05), controlling by cancer diagnosis. Analyzing stage (from I to IV) by breast cancer or not, we found a significant statistically difference (p < 0.001), 83.9% of breast cancer are stage I and II vs. 45.3% of no breast cancer. Conclusions: Our results suggest that a BMI ≥ 25 kg/m2 and diabetes are part of the profile of the Hispanic women with a diagnosis of a malignancy. Breast cancer is diagnosed at an earlier stage than any other malignancy, which could be explained by the amount of information available for breast cancer screening.

Background HCC patients are heterogeneous in terms of both tumor and liver factors. Alpha-fetoprotein (AFP) is an important prognostic tumor marker for those patients with elevated AFP levels. Aims To examine the differences in HCC patients with high or low AFP levels in blood and evaluate the prognostic parameters in low AFP patients. Methods A cohort of 2,440 HCC patients from 11 Italian medical centers was studied. AFP-positive patients were compared to AFP-negative ones, and the blood and tumor parameters of AFP-negative patients were examined. Results Low blood AFP levels were found in 58% of the total cohort, in 64% of patients with small HCCs, and in 51% of patients with large HCCs. In patients with large tumors, platelet and gamma glutamyl transpeptidase (GGTP) levels, tumor multifocality and portal vein thrombosis (PVT) incidence were all greater than in patients with small tumors, regardless of AFP status. Patients with higher AFP levels had worse survival rates than those with low AFP in each tumor size group. In patients with small tumors, the elevated AFP was associated with significantly increased PVT and worse survival. In patients with large tumors, the elevated AFP was associated with significantly higher GGTP, ALKP, and bilirubin levels, as well as with increased PVT and multifocality, and worse survival. Low-AFP patients with high GGTP levels had worse survival than patients with low GGTP levels. Conclusion Patients with low AFP were the majority in this cohort, and patients with elevated GGTP had worse prognosis than those with low GGTP. GGTP may be a useful tumor and prognosis marker in low-AFP patients. AFP-negative patients are important to identify due to their enhanced survival.

Cirrhosis-related abnormal liver function is associated with predisposition to hepatocellular carcinoma (HCC). It features in several HCC classification systems and is an HCC prognostic factor. The aim of the present study was to examine the phenotypic tumor differences in HCC patients with normal or abnormal plasma bilirubin levels. A 2,416-patient HCC cohort was studied and dichotomized into normal and abnormal plasma bilirubin groups. Their HCC characteristics were compared for tumor aggressiveness features, namely, blood alpha-fetoprotein (AFP) levels, tumor size, presence of portal vein thrombosis (PVT) and tumor multifocality. In the total cohort, elevated bilirubin levels were associated with higher AFP levels, increased PVT and multifocality, and lower survival, despite similar tumor sizes. When different tumor size terciles were compared, similar results were found, even among patients with small tumors. A multiple logistic regression model for PVT or tumor multifocality showed increased odds ratios for elevated levels of gamma glutamyl transpeptidase (GGTP), bilirubin, and AFP and for larger tumor sizes. We conclude that HCC patients with abnormal bilirubin levels had worse prognosis than patients with normal bilirubin. They also had an increased incidence of PVT and tumor multifocality, and higher AFP levels, in patients with both small and larger tumors. The results show an association between bilirubin levels and indices of HCC aggressiveness.

Aim of the study was to explore the response to a fluid challenge test (FCT) in normal subjects and in patients with pulmonary hypertension (PH). 168 subjects underwent right heart catheterization in basal conditions and after FCT. At baseline, 50 subjects showed normal pressures (healthy controls

Our attention was focused on the section dealing with the natural history of aortic stenosis (AS), particularly on these lines: “In most patients with severe AS, impaired platelet function and decreased levels of von Willebrand factor can be demonstrated. The severity of the coagulation abnormality correlates with the severity of AS and resolves after valve replacement . . . . After the onset of symptoms, average survival is 2 to 3 years, 10% to 11% with a high risk of sudden death. Thus, the development of symptoms identifies a critical point in the natural history of AS. The management decisions are based largely on these data; most clinicians treat asymptomatic patients conservatively, whereas corrective surgery is generally recommended in patients with symptoms thought to be due to AS. Symptoms may be subtle and often are not elicited by the physician in taking a routine clinical history

Acute toxic exposures in childhood are quite a frequent event in Paediatric Emergency Medicine. Despite that, there are few papers about clinical toxicology in children, at least in Italy. This paper is the first that takes into account both epidemiological aspects and clinical features of acute poisoning in children on a national basis. Collected data show the increased use of activated charcoal as a treatment and the use of the short stay observation unit as an appropriate answer to the real clinical situation, although some aspects are still controversial. It will be necessary to reconsider the whole matter widening the number of participating centres, so that the most controversial aspects may be clarified.

Metanephric adenomas are benign tumors frequently found post-mortem (from 7% to 22% of autopsies) which originate from distal tubules; they are generally small in dimensions (smaller than 1 cm) and located in the renal cortex. Etiology is unknown, even though they could be associated with smoke, tubular nephrosclerosis, dialysis. An endocrinal relationship was proposed, because of its more frequent incidence in female (2:1). Metanephric adenoma is an uncommon kind of renal adenoma with no malignant potentiality: from the clinical and diagnostic viewpoint its own greater importance depends on the probability of diagnostic misunderstanding with Wilms' tumor; furthermore its echographic, tomographic and arteriographic characteristics are often similar to small renal adenocarcinoma ones (100). Polycytemia is frequently associated to metanephric adenoma as paraneoplastic syndrome and, more rarely, abdominal mass, abdominal pain, hematuria and hypertension (140). The most important study on metanephric adenoma is the one realized by E.K. Mostofi, including 50 cases from the Department of Genitourinary Pathology, Armed Forces Institute of Pathology, Washington, D.C., published in 1995; in this study half of findings was incidental; mean dimension of tumor about 5,5 cm and in 50% it could be seen a distinct capsule sourrounding the tumor (in the remaining cases the capsule was discontinuos or absent) (210). An important radiological characteristic is that metanephric adenomas are more frequent calcificated than other histotypes and, from the pathological viewpoint, the most important differential element seems to be the smaller dimensions of its cells with hyperchromatic nuclei in the absence or lack in mitotic activity and in the absence of chromosome aberrations. In the case of difficult histological diagnosis, cytogenetic and immunohistochemical analysis can be useful. In conclusion, because it is impossible to distinguish in the preoperatory between the metaneprhic adenomas and the other tumoral types on the bases of the symptoms, dimensions or radiographic appearance, it is mandatory to treat it as malignant eteroformations in a therapeutical strategy, when it is possible.

Elective surgery cannot be recommended in every patient with asymptomatic severe aortic stenosis, and predictors identifying high-risk patients need to be identified. In guidelines we read that elective surgery, at the asymptomatic stage, can only be recommended in selected patients, at low operative risk (see guidelines of European Society of Cardiology and American Heart Association), but we have not read any reference to patients with severe calcific aortic stenosis after symptomatic spontaneous calcium cerebral embolism. Because cardioembolic stroke is associated with poor prognosis compared to other stroke subtypes, in patients with asymptomatic severe aortic stenosis and spontaneous calcific embolic stroke valve replacement appears to offer the best hope of avoiding a recidivation of stroke and should be considered in most cases. On the contrary, is it still correct to consider as asymptomatic patients with severe aortic stenosis and cerebral thromboembolism from a calcified aortic valve?

e11568 Background: Estrogen (ER), progesterone (PR) receptors and HER2 are important markers for breast cancer (BC) treatment planning. These markers are often measured by immunochemistry (IHC) but IHC is subject to limitations of operator subjectivity and equivocal results making selection of appropriate therapy difficult and ultimately affecting patient outcome. Methods: 135 females with BC were recruited in Puerto Rico between Sept and Dec 2012. Median patient age was 57 and 95 % had invasive ductal carcinoma. Our aim was to compare discordance rates of ER, PR and HER2 between IHC and AQUA, an automated fluorescent technology that quantifies antigen expression, in a population of Hispanic women and to investigate whether specimen type or tumor grade influence discordance rate between the two technologies. Results: 103 of 135 patient samples were found to be ER+ by both technologies and 28 samples were ER- by both IHC and AQUA. 4 samples (3%) were discordant; 2 each were AQUA+/IHC- and AQUA-/IHC+. 73 of 135 samples expressed PR by both technologies and 55 samples were PR- by both IHC and AQUA. 14 samples (10%) were discordant; 7 each were AQUA+/IHC- and AQUA-/IHC+. 87 of 135 samples were HER2- and 13 patients were found to be HER2+ by both technologies. However 35 samples (26%) were discordant for HER2 status; 31 were AQUA+/IHC- while 4 AQUA-/IHC+. 100 of the HER2 results were scored 0-1 (negative) by IHC and 25 % of these cases were overturned by AQUA to HER2 +. 19 of the HER2 results were scored 2 (borderline) by IHC. 32 % of these cases were positive by AQUA. Conclusions: Discordance rate were 3% for ER, 10 % for PR but 26% for HER2 between IHC and AQUA. The Cohen’s Kappa coefficient for ER and PR were 0.914 and 0.785 respectively but only 0.299 for HER2 (p values < 0.00001 for all 3 values). Needle/core biopsy yielded more HER2 discordance than lumpectomy/mastectomy (31% vs. 16%). HER2 discordance between IHC and AQUA was more common in higher grade tumors. The large number of HER2 negative IHC cases scored positive by AQUA, and considering the data demonstrating that HER2 by AQUA better predicts benefit from trastuzumab (Slamon D, SABCS 2012) suggests that a significant additional number of patients could benefit from such targeted therapy.

In November, 2008 a 13-year-old boy (weight 45 kg, height 160 cm) was taken by his parents to the emergency department. His parents reported that after school the boy had been agitated and aggressive, in contrast with his normal mood. He denied feeling stressed or having used drugs or stimulants. He complained of abdominal discomfort, increased diuresis, dysuria, and prickling sensations in his legs. On examination, he was restless, with sinus tachycardia (147 beats per min [bpm] on electrocardiogram [ECG]), tachypnoea (25 breaths per min), and raised blood pressure (145/90 mm Hg). Chest radiography and laboratory blood test results were normal. Toxicological screen was negative for cocaine, heroin, and amphetamine. Psychiatric consultation was unremarkable. Our patient’s condition improved overnight without any treatment and he was discharged the following morning. At discharge he was noted to have sinus bradycardia (40 bpm).Later that day, his mother returned to the emergency unit with two empty packets of stimulant (“energy”) chewing gum that she had found in her son’s bag; he had admitted consuming the confectionery at school. The chewing gum contained 160 mg caff eine per packet (0·57% caff eine per gum pellet) and non-specifi ed amounts of guarana