Restrictive cardiomyopathy and hypertrophic cardiomyopathy overlap: the importance of the phenotype

Restrictive cardiomyopathy (RCM) is defined on the basis of the haemodynamic finding of restrictive ventricular physiology. However, restrictive ventricular pathophysiology is also a feature of other subtypes of cardiomyopathy, including hypertrophic cardiomyopathy (HCM). Clinically and aetiologically, there is an overlap between RCM and HCM with restrictive physiology. However, the clinical distinction between these two entities can be an important pointer towards the underlying aetiology. This review highlights the importance of the recognition of the clinical phenotype as the first step in the classification of cardiomyopathies

Efficiency and costs of the health management in an organic dairy farm where we use unconventional medicines

The EU organic regulation explicitly promote the use of unconventional therapies, like homoeopathy and phytotherapy. The aim of the present study was to investigate the efficiency and the costs of these treatment methods. From December 2006 to September 2008, we analyzed the data recorded in an organic dairy farm where the animals are normally treated by classical unicistic homeopathy and phytotherapy, and only when indispensable, by allophaty, antiparasitic drugs, surgery and vaccines. The use of homeopathy resulted to be predominant in comparison with the others treatments. Besides, our trial showed that homeopathy and phytotherapy could be used to treat, with good outcomes, the majority of diseases that occur in a dairy cattle farm, even if, sometimes, conventional medicines have to be used. The costs for unconventional treatments are very low in comparison with conventional ones. This will allow the spreading of unconventional medicines in the Italian organic farms

GATA-1 as a Regulator of Mast Cell Differentiation Revealed by the Phenotype of the GATA-1low Mouse Mutant

Here it is shown that the phenotype of adult mice lacking the first enhancer (DNA hypersensitive site I) and the distal promoter of the GATA-1 gene (neoΔHS or GATA-1low mutants) reveals defects in mast cell development. These include the presence of morphologically abnormal alcian blue+ mast cells and apoptotic metachromatic− mast cell precursors in connective tissues and peritoneal lavage and numerous (60–70% of all the progenitors) “unique” trilineage cells committed to erythroid, megakaryocytic, and mast pathways in the bone marrow and spleen. These abnormalities, which were mirrored by impaired mast differentiation in vitro, were reversed by retroviral-mediated expression of GATA-1 cDNA. These data indicate an essential role for GATA-1 in mast cell differentiation

A Systematic Error in the Internal Friction Measurement of Coatings for Gravitational Waves Detectors

Low internal friction coatings are key components of advanced technologies such as optical atomic clocks and high-finesse optical cavity and often lie at the forefront of the most advanced experiments in Physics. Notably, increasing the sensitivity of gravitational-wave detectors depends in a very large part on developing new coatings, which entails developing more suitable methods and models to investigate their loss angle. In fact, the most sensitive region of the detection band in such detectors is limited by the coating thermal noise, which is related to the loss angle of the coating. Until now, models which describe only ideal physical properties have been adopted, wondering about the use of one or more loss angles to describe the mechanical properties of coatings. Here we show the presence of a systematic error ascribed to inhomogeneity of the sample at its edges in measuring the coating loss angle. We present a model for disk-shaped resonators, largely used in loss angle measurements, and we compare the theory with measurements showing how this systematic error impacts on the accuracy with which the loss model parameters are known

Detecting the gravito-magnetic field of the dark halo of the Milky Way - the LaDaHaD mission concept

We propose to locate transponders and atomic clocks in at least three of the Lagrange points of the Sun-Earth pair, with the aim of exploiting the time of flight asymme- try between electromagnetic signals travelling in opposite directions along polygonal loops having the Lagrange points at their vertices. The asymmetry is due to the pres- ence of a gravito-magnetic field partly caused by the angular momentum of the Sun, partly originating from the angular momentum of the galactic dark halo in which the Milky Way is embedded. We list also various opportunities which could be associated with the main objective of this Lagrange Dark Halo Detector (LaDaHaD)

Prognostic value of the fibrosis-4 index in human immunodeficiency virus type-1 infected patients initiating antiretroviral therapy with or without hepatitis C virus

Objective: To evaluate the Fibrosis (FIB)-4 index as a predictor of major liver-related events (LRE) and liver-related death (LRD) in human immunodeficiency virus (HIV) type-1 patients initiating combination antiretroviral therapy (cART). Design: Retrospective analysis of a prospective cohort study. Setting: Italian HIV care centers participating to the ICONA Foundation cohort. Participants: Treatment-naive patients enrolled in ICONA were selected who: initiated cART, had hepatitis C virus (HCV) serology results, were HBsAg negative, had an available FIB-4 index at cART start and during follow up. Methods: Cox regression models were used to determine the association of FIB4 with the risk of major LRE (gastrointestinal bleeding, ascites, hepatic encephalopathy, hepato-renal syndrome or hepatocellular carcinoma) or LRD. Results: Three-thousand four-hundred seventy-five patients were enrolled: 73.3% were males, 27.2% HCV seropositive. At baseline (time of cART initiation) their median age was 39 years, had a median CD4+ T cell count of 260 cells/uL, and median HIV RNA 4.9 log copies/mL, 65.9% had a FIB-4 <1.45, 26.4% 1.45–3.25 and 7.7% >3.25. Over a follow up of 18,662 person-years, 41 events were observed: 25 major LRE and 16 LRD (incidence rate, IR, 2.2 per 1,000 PYFU [95% confidence interval, CI 1.6–3.0]). IR was higher in HCV seropositives as compared to negatives (5.9 vs 0.5 per 1,000 PYFU). Higher baseline FIB-4 category as compared to <1.45 (FIB-4 1.45–3.25: HR 3.55, 95% CI 1.09–11.58; FIB-4 >3.25: HR 4.25, 1.21–14.92) and time-updated FIB-4 (FIB-4 1.45–3.25: HR 3.40, 1.02–11.40; FIB-4 >3.25: HR 21.24, 6.75–66.84) were independently predictive of major LRE/LRD, after adjusting for HIV- and HCV-related variables, alcohol consumption and type of cART. Conclusions: The FIB-4 index at cART initiation, and its modification over time are risk factors for major LRE or LRD, independently of infection with HCV and could be used to monitor patients on cART

Impact of antiretroviral dosing and daily pill burden on viral rebound rates in naive patients receiving a tenofovir-based regimen

Methods A total of 480 ART-naive patients were selected from the GNOMO cohort. Incidence rate of viral rebound (VR = first of two consecutive VL>50 cp/ml) was calculated as number of events over PYFU and expressed at univariate and multivariate analysis as incidence rate ratio (IRR). Number of both pills and doses per day were used to define three different types of regimens: twice-a-day regimens (BID regimens); once-a-day regimens with 3 pills (high-pill QD [hp-QD]). Adjusted rates of viral rebound were estimated by Poisson regression using date of first HIV-RNA <50 c/ml as baseline. Follow-up was censored at the date of VR, death, or loss to follow-up

Sex-related differences in risk factors, type of treatment received and outcomes in patients with atrial fibrillation and acute stroke: Results from the RAF-study (Early Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation)

Introduction: Atrial fibrillation is an independent risk factor of thromboembolism. Women with atrial fibrillation are at a higher overall risk for stroke compared to men with atrial fibrillation. The aim of this study was to evaluate for sex differences in patients with acute stroke and atrial fibrillation, regarding risk factors, treatments received and outcomes. Methods Data were analyzed from the “Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation” (RAF-study), a prospective, multicenter, international study including only patients with acute stroke and atrial fibrillation. Patients were followed up for 90 days. Disability was measured by the modified Rankin Scale (0–2 favorable outcome, 3–6 unfavorable outcome). Results: Of the 1029 patients enrolled, 561 were women (54.5%) (p &lt; 0.001) and younger (p &lt; 0.001) compared to men. In patients with known atrial fibrillation, women were less likely to receive oral anticoagulants before index stroke (p = 0.026) and were less likely to receive anticoagulants after stroke (71.3% versus 78.4%, p = 0.01). There was no observed sex difference regarding the time of starting anticoagulant therapy between the two groups (6.4 ± 11.7 days for men versus 6.5 ± 12.4 days for women, p = 0.902). Men presented with more severe strokes at onset (mean NIHSS 9.2 ± 6.9 versus 8.1 ± 7.5, p &lt; 0.001). Within 90 days, 46 (8.2%) recurrent ischemic events (stroke/TIA/systemic embolism) and 19 (3.4%) symptomatic cerebral bleedings were found in women compared to 30 (6.4%) and 18 (3.8%) in men (p = 0.28 and p = 0.74). At 90 days, 57.7% of women were disabled or deceased, compared to 41.1% of the men (p &lt; 0.001). Multivariate analysis did not confirm this significance. Conclusions: Women with atrial fibrillation were less likely to receive oral anticoagulants prior to and after stroke compared to men with atrial fibrillation, and when stroke occurred, regardless of the fact that in our study women were younger and with less severe stroke, outcomes did not differ between the sexes

Prediction of early recurrent thromboembolic event and major bleeding in patients with acute stroke and atrial fibrillation by a risk stratification schema: the ALESSA score study

Background and Purposes—This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. Methods—The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00–1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08–2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P=0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30–1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion &#62;1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632–0.763; P=0.0001) for ischemic outcome events and 0.585 (0.493–0.678; P=0.10) for major bleedings. Results—The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529–0.763; P=0.009) for ischemic outcome events and 0.407 (0.275–0.540; P=0.14) for hemorrhagic outcome events. Conclusions—In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings

Comparison and combination of a hemodynamics/biomarkers-based model with simplified PESI score for prognostic stratification of acute pulmonary embolism: findings from a real world study

Background: Prognostic stratification is of utmost importance for management of acute Pulmonary Embolism (PE) in clinical practice. Many prognostic models have been proposed, but which is the best prognosticator in real life remains unclear. The aim of our study was to compare and combine the predictive values of the hemodynamics/biomarkers based prognostic model proposed by European Society of Cardiology (ESC) in 2008 and simplified PESI score (sPESI).Methods: Data records of 452 patients discharged for acute PE from Internal Medicine wards of Tuscany (Italy) were analysed. The ESC model and sPESI were retrospectively calculated and compared by using Areas under Receiver Operating Characteristics (ROC) Curves (AUCs) and finally the combination of the two models was tested in hemodinamically stable patients. All cause and PE-related in-hospital mortality and fatal or major bleedings were the analyzed endpointsResults: All cause in-hospital mortality was 25% (16.6% PE related) in high risk, 8.7% (4.7%) in intermediate risk and 3.8% (1.2%) in low risk patients according to ESC model. All cause in-hospital mortality was 10.95% (5.75% PE related) in patients with sPESI score ≥1 and 0% (0%) in sPESI score 0. Predictive performance of sPESI was not significantly different compared with 2008 ESC model both for all cause (AUC sPESI 0.711, 95% CI: 0.661-0.758 versus ESC 0.619, 95% CI: 0.567-0.670, difference between AUCs 0.0916, p=0.084) and for PE-related mortality (AUC sPESI 0.764, 95% CI: 0.717-0.808 versus ESC 0.650, 95% CI: 0.598-0.700, difference between AUCs 0.114, p=0.11). Fatal or major bleedings occurred in 4.30% of high risk, 1.60% of intermediate risk and 2.50% of low risk patients according to 2008 ESC model, whereas these occurred in 1.80% of high risk and 1.45% of low risk patients according to sPESI, respectively. Predictive performance for fatal or major bleeding between two models was not significantly different (AUC sPESI 0.658, 95% CI: 0.606-0.707 versus ESC 0.512, 95% CI: 0.459-0.565, difference between AUCs 0.145, p=0.34). In hemodynamically stable patients, the combined endpoint in-hospital PE-related mortality and/or fatal or major bleeding (adverse events) occurred in 0% of patients with low risk ESC model and sPESI score 0, whilst it occurred in 5.5% of patients with low-risk ESC model but sPESI ≥1. In intermediate risk patients according to ESC model, adverse events occurred in 3.6% of patients with sPESI score 0 and 6.65% of patients with sPESI score ≥1.Conclusions: In real world, predictive performance of sPESI and the hemodynamic/biomarkers-based ESC model as prognosticator of in-hospital mortality and bleedings is similar. Combination of sPESI 0 with low risk ESC model may identify patients with very low risk of adverse events and candidate for early hospital discharge or home treatment.