Disruption of transfer entropy and inter-hemispheric brain functional connectivity in patients with disorder of consciousness

Severe traumatic brain injury can lead to disorders of consciousness (DOC) characterized by deficit in conscious awareness and cognitive impairment including coma, vegetative state, minimally consciousness, and lock-in syndrome. Of crucial importance is to find objective markers that can account for the large-scale disturbances of brain function to help the diagnosis and prognosis of DOC patients and eventually the prediction of the coma outcome. Following recent studies suggesting that the functional organization of brain networks can be altered in comatose patients, this work analyzes brain functional connectivity (FC) networks obtained from resting-state functional magnetic resonance imaging (rs-fMRI). Two approaches are used to estimate the FC: the Partial Correlation (PC) and the Transfer Entropy (TE). Both the PC and the TE show significant statistical differences between the group of patients and control subjects; in brief, the inter-hemispheric PC and the intra-hemispheric TE account for such differences. Overall, these results suggest two possible rs-fMRI markers useful to design new strategies for the management and neuropsychological rehabilitation of DOC patients.Comment: 25 pages; 4 figures; 3 tables; 1 supplementary figure; 4 supplementary tables; accepted for publication in Frontiers in Neuroinformatic

Accurate Real-Time PCR Strategy for Monitoring Bloodstream Parasitic Loads in Chagas Disease Patients

Infection with the parasite Trypanosoma cruzi (T. cruzi), causing American trypanosomiasis or Chagas disease, remains a major public health concern in 21 endemic countries of America, with an estimated prevalence of 8 million infected people. Chagas disease shows a variable clinical course, ranging from asymptomatic to chronic stages with low parasitaemias, whose severest form is heart disease. Diagnosis at the asymptomatic and chronic stages is based on serological detection of anti-T. cruzi antibodies, because conventional parasitological methods lack sensitivity. Current chemotherapies are more effective in recent infections than in the chronic adult population. The criterion of cure relies on serological conversion to negative, which may occur only years after treatment, requiring long-term follow-up. In this context, we aimed to develop a real-time PCR assay targeted to repetitive sequences of T. cruzi for sensitive quantitation of parasitic load in peripheral blood of infected patients. It was applied to monitor treatment response of infected children, allowing rapid evaluation of drug efficacy as well as detection of treatment failure. It was also used for early diagnosis of chagasic reactivation in end-stage heart disease patients who received immunosuppressive drugs after cardiac transplantation. This laboratory strategy may constitute a novel parasitological tool for prompt and sensitive evaluation of anti-parasitic treatment of Chagas disease

A trial to evaluate the effect of the sodium–glucose co‐transporter 2 inhibitor dapagliflozin on morbidity and mortality in patients with heart failure and reduced left ventricular ejection fraction (DAPA‐HF)

Background: Sodium–glucose co‐transporter 2 (SGLT2) inhibitors have been shown to reduce the risk of incident heart failure hospitalization in individuals with type 2 diabetes who have, or are at high risk of, cardiovascular disease. Most patients in these trials did not have heart failure at baseline and the effect of SGLT2 inhibitors on outcomes in individuals with established heart failure (with or without diabetes) is unknown. Design and methods: The Dapagliflozin And Prevention of Adverse‐outcomes in Heart Failure trial (DAPA‐HF) is an international, multicentre, parallel group, randomized, double‐blind, study in patients with chronic heart failure, evaluating the effect of dapagliflozin 10 mg, compared with placebo, given once daily, in addition to standard care, on the primary composite outcome of a worsening heart failure event (hospitalization or equivalent event, i.e. an urgent heart failure visit) or cardiovascular death. Patients with and without diabetes are eligible and must have a left ventricular ejection fraction ≤ 40%, a moderately elevated N‐terminal pro B‐type natriuretic peptide level, and an estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2. The trial is event‐driven, with a target of 844 primary outcomes. Secondary outcomes include the composite of total heart failure hospitalizations (including repeat episodes), and cardiovascular death and patient‐reported outcomes. A total of 4744 patients have been randomized. Conclusions: DAPA‐HF will determine the efficacy and safety of the SGLT2 inhibitor dapagliflozin, added to conventional therapy, in a broad spectrum of patients with heart failure and reduced ejection fraction

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

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

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 &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 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

Terapia de Resincronización Cardiaca.

En este artículo de revisión, se aborda el tema de la terapia de resincronización cardiaca, como un nuevo recurso terapéutico ante el síndrome terminal de la insuficiencia cardíaca congestiva grave, refractaria al tratamiento médico óptimo. En una aproximación al tema se exponen los fundamentos de tal tipo de terapéutica, los criterios de selección de pacientes, la definición de “respondedores” y el papel de la ecocardiografía en la evaluación de disincronía mecánica. Asimismo se refiere el papel de la ecocardiografía en la optimización de la programación de los resincronizadores y, finalmente, se hace una breve referencia a los efectos de la terapia de resincronización cardíaca y a los estudios más importantes al respecto

Terapia de Resincronización Cardiaca.

En este artículo de revisión, se aborda el tema de la terapia de resincronización cardiaca, como un nuevo recurso terapéutico ante el síndrome terminal de la insuficiencia cardíaca congestiva grave, refractaria al tratamiento médico óptimo. En una aproximación al tema se exponen los fundamentos de tal tipo de terapéutica, los criterios de selección de pacientes, la definición de “respondedores” y el papel de la ecocardiografía en la evaluación de disincronía mecánica. Asimismo se refiere el papel de la ecocardiografía en la optimización de la programación de los resincronizadores y, finalmente, se hace una breve referencia a los efectos de la terapia de resincronización cardíaca y a los estudios más importantes al respecto

Participación de la Argentina en el Registro Europeo de Insuficiencia Cardíaca

Background: Heart failure is a globally expanding disease and the available therapeutic tools are still insufficient. Objectives: The aim of this study was to know the epidemiological and clinical characteristics of patients with diagnosis of heart failure in the Argentine Republic, as well as the treatments implemented and their prognosis, both in outpatients and hospitalized patients due to disease recurrence. Methods: An observational, prospective, multicenter study of outpatients with chronic heart failure and hospitalized patients admitted due to decompensated heart failure was performed in the Argentine Republic from August 2012 to March 2013, in order to participate in the long-term Heart Failure Registry organized by the European Society of Cardiology. To facilitate recruitment, the study design contemplated inclusion only one day per week. Patients were followed up for one year. Results: A total of 492 patients were included: 122 with decompensated heart failure and 370 with chronic heart failure. In both groups, women accounted for 30%. Compared with outpatients, hospitalized patients were older [72.5 years (IQR 64-80) vs. 63 years (IQR 54-71); p <0.0001] and with a higher risk clinical profile. Atrial fibrillation and preserved ejection fraction were more frequent in hospitalized patients. Median hospitalization time was 5 days and in-hospital mortality was 2.5%. At one year follow-up, 20.8% of patients recruited at hospital admission and 10.3% of outpatients died. The rate of readmission for decompensated heart failure was 45.6% and that of hospitalization for chronic heart failure was 28%.Introducción: La insuficiencia cardíaca es una patología que se encuentra en expansión a nivel global y las herramientas terapéuticas disponibles aún son insuficientes. Objetivos: Conocer las características epidemiológicas y clínicas de los pacientes con diagnóstico de insuficiencia cardíaca en la República Argentina, así como las terapéuticas implementadas y su pronóstico, tanto en pacientes ambulatorios como en internados por una reagudización. Material y métodos: Se realizó un relevamiento observacional, prospectivo multicéntrico de pacientes con insuficiencia cardíaca crónica ambulatorios e internados por insuficiencia cardíaca descompensada en la República Argentina durante el período agosto 2012-marzo 2013, reclutados para participar en el Registro a largo plazo de Insuficiencia Cardíaca organizado por la Sociedad Europea de Cardiología. Para facilitar el reclutamiento, el diseño contempló la inclusión solamente un día semanal. Se realizó seguimiento al año de los pacientes. Resultados: Se incluyeron 492 pacientes, de los cuales 122 correspondieron a insuficiencia cardíaca descompensada y 370 a insuficiencia cardíaca crónica. En ambos grupos, las mujeres representaron el 30%. Comparados con los ambulatorios, los internados tuvieron mayor edad [72,5 años (RIC 64-80) vs. 63 años (RIC 54-71); p < 0,0001] y un perfil clínico de mayor riesgo. La fibrilación auricular y la fracción de eyección preservada fueron más frecuentes en los internados. La mediana de internación fue de 5 días y la mortalidad hospitalaria fue del 2,5%. Al año de seguimiento fallecieron el 20,8% de los reclutados en la internación y el 10,3% de los ambulatorios. La tasa de readmisión para insuficiencia cardíaca descompensada fue del 45,6% y la de hospitalización para insuficiencia cardíaca crónica fue del 28%. Conclusiones: Las poblaciones de pacientes internados y ambulatorios no fueron homogéneas; los hospitalizados tuvieron mayor edad y fue más prevalente la insuficiencia cardíaca con fracción de eyección preservada. La tasa de eventos en el seguimiento a 12 meses fue elevada y aun mayor para aquellos con insuficiencia cardíaca descompensada