Deep phenotyping and genomic data from a nationally representative study on dementia in India

The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) is a nationally representative in-depth study of cognitive aging and dementia. We present a publicly available dataset of harmonized cognitive measures of 4,096 adults 60 years of age and older in India, collected across 18 states and union territories. Blood samples were obtained to carry out whole blood and serum-based assays. Results are included in a venous blood specimen datafile that can be linked to the Harmonized LASI-DAD dataset. A global screening array of 960 LASI-DAD respondents is also publicly available for download, in addition to neuroimaging data on 137 LASI-DAD participants. Altogether, these datasets provide comprehensive information on older adults in India that allow researchers to further understand risk factors associated with cognitive impairment and dementia.Peer reviewe

Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial

Background. Pediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM. Methods. TBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL). Results. Of 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P < .01). Conclusions. In a pediatric TBM trial, functional outcomes were excellent overall. The trend toward higher frequency of adverse events but better neurocognitive outcomes in children receiving high-dose rifampicin requires confirmation in a larger trial. Clinical Trials Registration. NCT02958709

Advanced Heart Failure Management and Transplantation

Hypertrophic cardiomyopathy is a genetic heart disease with heterogeneous clinical features, including progression to advanced heart failure. The development of these symptoms can be related to outflow obstruction but in some patients reflects an underlying process of fibrosis and progressive ventricular dysfunction. For patients with end-stage disease, traditional heart failure therapies have not proved beneficial. As such, more advanced therapies, such as left ventricular assist device or cardiac transplantation, should be considered for these patients. Although left ventricular assist device support is used infrequently due to the restrictive physiology underlying hypertrophic cardiomyopathy, transplant represents an effective treatment, with encouraging long-term outcome data

Use of Levosimendan in Acute and Advanced Heart Failure: Short Review on Available Real-World Data

Published data have shown potential advantages of levosimendan in the management of acute decompensated heart failure and advanced heart failure when standard medical therapies threaten hemodynamics and organ perfusion are unable to alleviate clinical symptoms. Levosimendan distinguishes itself from other catecholaminergic inotropes by its three mechanisms of action: positive inotropy, vasodilation, and cardioprotection. In addition, its pharmacokinetics allow for a longer duration of action from the metabolite OR1896 allowing for further cardiovascular therapeutic effects for several days, even after discontinuation of the parent drug

Role of Micro RNA in Heart Transplant

The need for noninvasive biomarkers for diagnostic, prognostic, and therapeutic purposes is increasingly being recognized in the field of heart transplantation. MicroRNAs are a class of novel biomarkers that control gene expression and influence cellular functions, including differentiation, proliferation, and functional regulation of the immune system. They can be detected in the serum, plasma, and urine and may serve as early noninvasive biomarkers for various disease processes. Despite significant advances in heart transplantation, challenges remain in the short and long term with early graft injury and dysfunction, both cellular and antibody-mediated rejection, infections of varying types and severity, and cardiac allograft vasculopathy, which require an interventional approach for diagnosis and management. In this article, we review the current knowledge on the role of microRNAs in heart transplantation and its related complications and discuss their potential impact in future strategies to manage heart transplantation

Left Ventricular Assist Device in Older Adults

Left ventricular assist devices (LVADs) are an effective therapy for a growing and aging population in the background of limited donor supply. Selecting the proper patient involves assessment of indications, risk factors, scores for overall outcomes, assessment for right ventricular failure, and optimal timing of implantation. LVAD complications have a 5% to 10% perioperative mortality and complications of bleeding, thrombosis, stroke, infection, right ventricular failure, and device failure. As LVAD engineering technology evolves, so will the risk-prediction scores. Hence, more large-scale prospective data from multicenters will continually be required to aid in patient selection, reduce complications, and improve long-term outcomes

Mineralocorticoid Receptor Antagonist Use in Heart Failure With Reduced Ejection Fraction and End-Stage Renal Disease Patients on Dialysis: A Literature Review

Mineralocorticoid receptor antagonists (MRAs) are known to have a proven mortality benefit in heart failure with reduced ejection fraction (HFrEF) without kidney disease. As patients with end-stage renal disease (ESRD) requiring either peritoneal dialysis or hemodialysis were excluded in clinical trials of HFrEF, the data are scant on the appropriate use of MRAs in this population. The unknown efficacy, along with concerns of adverse effects such as hyperkalemia, has limited the willingness of clinicians to consider using MRAs in these patients. However, it is unclear whether the risk of hyperkalemia is present if a patient is oliguric or anuric. Current guidelines recommend against the use of MRAs in patients with chronic kidney disease, but do not address the use of MRAs in patients requiring dialysis. This article will review the epidemiology of heart failure in ESRD, the pathophysiological derangements of the renin-angiotensin-aldosterone system in patients with kidney disease, and the results from case series and trials of the use of MRAs in ESRD with HFrEF. Although limited to several small trials using MRAs in peritoneal and hemodialysis patients with or without HFrEF, the current literature appears to show the potential for clinical benefits with little risk

High Flow From Impella 5.5 With Partial Veno-Arterial Extracorporeal Membrane Oxygenation Support: Case Series

Optimal flow balance between Impella 5.5 and veno-arterial extracorporeal membrane oxygenation (ECMO) support in the setting of EC-PELLA (ECMO+Impella) is unknown. Outcomes of high Impella 5.5 flow in the setting of EC-PELLA support were reviewed (N = 7). EC-PELLA was successfully explanted in 6 patients (bridge-to-transplant, N = 1; bridge-to-recovery, N = 5). The median duration of EC-PELLA support in explanted patients was 6 days. Survival at discharge was 71.4% (5 patients). In terms of device-related events, either VA-ECMO or Impella-related complications were not experienced. The median performance level of Impella 5.5 was P5 at the time of starting EC-PELLA support and then increased with time up to the median of P8 with increment of the Impella flow, and index (L/min/m ). The percentage of Impella flow per total EC- PELLA flow reached 50% after 48 h of support. The vasoactive-inotropic score and serum lactate level improved after institution of EC-PELLA support as well as the pulmonary artery pressures and central venous pressure. In conclusion, a high pump flow from Impella 5.5 with partial VA-ECMO support in the setting of EC-PELLA provided great support with favorable survival and device-related complications rate