Infecção natural pelo Trypanosoma cruzi em cães de áreas endêmicas da República Argentina

The population dynamics and the prevalence of chagasic infection of 352 dogs living in 108 rural houses infested by triatomines were studied. The region was divided into three sections according to increasing distances to an urban area. Each animal was identified by means of its particular characteristics and built, and its owners gave information about its habits. By means of xenodiagnosis, serology and ECG studies, prevalences of infection, parasitological-serological correlation, percentage of altered electrocardiographic outlines and percentage of houses with parasitemic dogs, were determined. The rural area showed a characteristic T. cruzi infection pattern and differences in the canine population parameters with respect to the other areas were observed: a higher proportion of puppies than adult dogs, a more sedentary population, higher prevalences of infection, as measured by xenodiagnosis, in dogs, and the highest proportion of bedroom insects infected with T. cruzi. It is assumed that the sedentary characteristics of the human population in that rural area impinge in the blood offer to the triatomine population, and the high percentage of parasitemic dogs of the area, contribute to the rise of "kissing ougs" infected with T. cruzi found in bedrooms.Estudou-se a dinâmica populacional e a prevalência de infecção chagásica de 352 cães vivendo em 108 moradias rurais infestadas por triato-míneos. A área foi dividida em três setores de acordo com suas crescentes distâncias em relação a um povoado urbano. Cada animal foi identificado mediante suas características particulares, e seus donos deram informações a respeito de seus hábitos. As prevalências de infecção foram determinadas por sorologia, correlação parasitológica-sorológica, percentual de traçados eletrocardiográficos alterados e o percentual de moradias com cães parasitados. A área rural mostrou um padrão característico de infecção por T. cruzi e observaram-se diferenças nos parâmetros de população canina em relação às restantes áreas: maior proporção de filhotes, maior população humana e canina sedentárias, maiores prevalências de infecção por xenodiagnóstico em cães e maior proporção de barbeiros infectados com T. cruzi nos cômodos da casa. Supõe-se que as características sedentárias da população humana desta área rural é fundamental para a oferta de sangue para as populações triatomíneas, e a elevada porcentagem de cães parasitêmicos dessa área contribui para o aumento de barbeiros infectados com T. cruzi encontrados nos quartos de dormir

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

A atividade da azitromicina contra a Leishmania (Viannia) braziliensise a Leishmania (Leishmania) amazonensis no modelogolden hamster

Fil: Sinagra, Angel. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Luna, Concepción. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Abraham, David. Thomas Jefferson University. Department of Microbiology and Immunology; Estados Unidos.Fil: Riarte, Adelina. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología Dr. Mario Fatala Chaben; Argentina.Fil: Iannella, María del Carmen. Universidad de Buenos Aires. Departamento de Matemática; Argentina.Fil: Krolewiecki, Alejandro J. Fundación Huésped. Área de Investigaciones Clínicas; Argentina.New therapeutic alternatives against leishmaniasis remain a priority. The activity of azithromycin against Leishmania(Leishmania) major has been previously demonstrated. Different responses among species of Leishmaniamake species-specific drug screening necessary. The activity of azithromycin against Leishmania (Viannia) braziliensisand Leishmania (Leishmania) amazonensiswas evaluated in golden hamsters infected through footpad injections of metacyclic promastigotes, and compared with untreated controls and animals treated with meglumine antimoniate. Footpad thickness, lesion cultures and dissemination sites were analyzed. Treatment of golden hamsters with oral azithromycin at 450mg/kg had no activity against infections with Leishmania (Leishmania) amazonensis. For infections due to Leishmania (Viannia) braziliensis, azithromycin demonstrated significant activity relative to untreated controls, but inferior to meglumine antimoniate, for controlling lesion size. Neither drug was able to totally eliminate parasites from the lesions. It was concluded that azithromycin has activity against Leishmania (Viannia) braziliensisbut not against Leishmania (Leishmania) amazonensisin this model

A atividade da azitromicina contra a Leishmania (Viannia) braziliensise a Leishmania (Leishmania) amazonensis no modelogolden hamster

Fil: Sinagra, Angel. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Luna, Concepción. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Abraham, David. Thomas Jefferson University. Department of Microbiology and Immunology; Estados Unidos.Fil: Riarte, Adelina. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología Dr. Mario Fatala Chaben; Argentina.Fil: Iannella, María del Carmen. Universidad de Buenos Aires. Departamento de Matemática; Argentina.Fil: Krolewiecki, Alejandro J. Fundación Huésped. Área de Investigaciones Clínicas; Argentina.New therapeutic alternatives against leishmaniasis remain a priority. The activity of azithromycin against Leishmania(Leishmania) major has been previously demonstrated. Different responses among species of Leishmaniamake species-specific drug screening necessary. The activity of azithromycin against Leishmania (Viannia) braziliensisand Leishmania (Leishmania) amazonensiswas evaluated in golden hamsters infected through footpad injections of metacyclic promastigotes, and compared with untreated controls and animals treated with meglumine antimoniate. Footpad thickness, lesion cultures and dissemination sites were analyzed. Treatment of golden hamsters with oral azithromycin at 450mg/kg had no activity against infections with Leishmania (Leishmania) amazonensis. For infections due to Leishmania (Viannia) braziliensis, azithromycin demonstrated significant activity relative to untreated controls, but inferior to meglumine antimoniate, for controlling lesion size. Neither drug was able to totally eliminate parasites from the lesions. It was concluded that azithromycin has activity against Leishmania (Viannia) braziliensisbut not against Leishmania (Leishmania) amazonensisin this model

International Prospective Registry of Acute Coronary Syndromes in Patients With COVID-19

Background Published data suggest worse outcomes in acute coronary syndrome (ACS) patients and concurrent coronavirus disease 2019 (COVID-19) infection. Mechanisms remain unclear. Objectives The purpose of this study was to report the demographics, angiographic findings, and in-hospital outcomes of COVID-19 ACS patients and compare these with pre–COVID-19 cohorts. Methods From March 1, 2020 to July 31, 2020, data from 55 international centers were entered into a prospective, COVID-ACS Registry. Patients were COVID-19 positive (or had a high index of clinical suspicion) and underwent invasive coronary angiography for suspected ACS. Outcomes were in-hospital major cardiovascular events (all-cause mortality, re–myocardial infarction, heart failure, stroke, unplanned revascularization, or stent thrombosis). Results were compared with national pre–COVID-19 databases (MINAP [Myocardial Ischaemia National Audit Project] 2019 and BCIS [British Cardiovascular Intervention Society] 2018 to 2019). Results In 144 ST-segment elevation myocardial infarction (STEMI) and 121 non–ST-segment elevation acute coronary syndrome (NSTE-ACS) patients, symptom-to-admission times were significantly prolonged (COVID-STEMI vs. BCIS: median 339.0 min vs. 173.0 min; p < 0.001; COVID NSTE-ACS vs. MINAP: 417.0 min vs. 295.0 min; p = 0.012). Mortality in COVID-ACS patients was significantly higher than BCIS/MINAP control subjects in both subgroups (COVID-STEMI: 22.9% vs. 5.7%; p < 0.001; COVID NSTE-ACS: 6.6% vs. 1.2%; p < 0.001), which remained following multivariate propensity analysis adjusting for comorbidities (STEMI subgroup odds ratio: 3.33 [95% confidence interval: 2.04 to 5.42]). Cardiogenic shock occurred in 20.1% of COVID-STEMI patients versus 8.7% of BCIS patients (p < 0.001). Conclusions In this multicenter international registry, COVID-19–positive ACS patients presented later and had increased in-hospital mortality compared with a pre–COVID-19 ACS population. Excessive rates of and mortality from cardiogenic shock were major contributors to the worse outcomes in COVID-19 positive STEMI patients

Are hospitalized or ambulatory patients with heart failure treated in accordance with European Society of Cardiology guidelines? Evidence from 12 440 patients of the ESC Heart Failure Long-Term Registry.

AIMS: To evaluate how recommendations of European guidelines regarding pharmacological and non-pharmacological treatments for heart failure (HF) are adopted in clinical practice. METHODS AND RESULTS: The ESC-HF Long-Term Registry is a prospective, observational study conducted in 211 Cardiology Centres of 21 European and Mediterranean countries, members of the European Society of Cardiology (ESC). From May 2011 to April 2013, a total of 12 440 patients were enrolled, 40.5% with acute HF and 59.5% with chronic HF. Intravenous treatments for acute HF were heterogeneously administered, irrespective of guideline recommendations. In chronic HF, with reduced EF, renin-angiotensin system (RAS) blockers, beta-blockers, and mineralocorticoid antagonists (MRAs) were used in 92.2, 92.7, and 67.0% of patients, respectively. When reasons for non-adherence were considered, the real rate of undertreatment accounted for 3.2, 2.3, and 5.4% of the cases, respectively. About 30% of patients received the target dosage of these drugs, but a documented reason for not achieving the target dosage was reported in almost two-thirds of them. The more relevant reasons for non-implantation of a device, when clinically indicated, were related to doctor uncertainties on the indication, patient refusal, or logistical/cost issues. CONCLUSION: This pan-European registry shows that, while in patients with acute HF, a large heterogeneity of treatments exists, drug treatment of chronic HF can be considered largely adherent to recommendations of current guidelines, when the reasons for non-adherence are taken into account. Observations regarding the real possibility to adhere fully to current guidelines in daily clinical practice should be seriously considered when clinical practice guidelines have to be written