Heart failure in children studied in relation to its causes and outcome

To identify the aetiology and outcome of congestive heart failure in children, a prospective study was carried out in the department of paediatric medicine, Medical College, Kolkata among 0-12 years children with documented signs and symptoms of heart failure. Proper history taking, physical examination, chest x-ray, ECG, echocardiography and maintenance of management records were done. A total of 350 cases were enrolled. Congenital heart disease was seen in 34% cases and the rest were due to acquired heart disease. Anaemia was detected in 17.4% cases. Mortality was 2.85%.     

PAR-1 antagonists: current state of evidence

Vorapaxar (SCH 530348) and atopaxar (E5555) are oral protease-activated receptor-1 (PAR-1) antagonists with high bioavailability. They inhibits thrombin induced platelet aggregation by competitively inhibiting PAR-1. We systematically evaluated the evidence for the efficacy and safety of all PAR-1 antagonists as well as for the individual drugs vorapaxar and atopaxar in different databases—PubMed, EMBASE, Scopus, and Cochrane register of Controlled Clinical Trials (CENTRAL).We selected randomized controlled trials of PAR-1 antagonists that reported on cardiovascular mortality as a clinical outcome. The random-effects Mantel–Haenszel model was used to evaluate the effect of PAR-1 antagonists on cardiovascular mortality. Seven trials were selected (N = 42,355) for analysis. PAR-1 antagonists as a class, as well as individually, were associated with a non-significant numerically lower risk of cardiovascular mortality than that seen with agents used in the control group; RR, 0.93; 95 % CI, 0.83–1.04; P = 0.20). No heterogeneity was noted. However, PAR-1 antagonists also appeared to increase the risk of bleeding significantly. PAR-1 antagonists appear to be associated with some reduction in the risk of cardiovascular mortality; however the significantly higher bleeding risk noted with PAR-1 antagonists appear to mandate a very careful selection of patients that may benefit without a substantially increased risk of bleeds.     

Biochemical and pathological characterization of frontotemporal dementia due to a Leu266Val mutation in microtubule-associated protein tau in an African American individual

Frontotemporal dementia (FTD) is a clinically heterogeneous disorder characterized by alterations in language and/or behavior, often in association with Parkinsonism or motor neuron disease. A familial form of FTD is associated with mutations in the microtubule-associated protein tau (MAPT) gene. We report here on the clinical, neuroimaging, cerebral spinal fluid biomarker, genetic, biochemical and postmortem neuropathological analyses of a case of familial FTD with a Leu266Val MAPT mutation which results in a very early age of onset and a rapid course of disease. This is also the first reported case of any MAPT mutation in an individual of African American ethnicity. Grant Acknowledgement: The research reported here was supported by grants AG17586, AG10124, NS44266, K08 NS14108, and K08 AG20073 from the National Institutes on Aging and Neurological Disorders and Stroke of the National Institutes of Health, Department of Health and Human Services.