BCKDK loss impairs mitochondrial Complex I activity and drives alpha-synuclein aggregation in models of Parkinson's disease.

Mitochondrial dysfunction and α-synuclein (αSyn) aggregation are key contributors to Parkinson's Disease (PD). While genetic and environmental risk factors, including mutations in mitochondrial-associated genes, are implicated in PD, the precise mechanisms linking mitochondrial defects to αSyn pathology remain incompletely understood, hindering the development of effective therapeutic interventions. Here, we identify the loss of branched chain ketoacid dehydrogenase kinase (BCKDK) as a mitochondrial risk factor that exacerbates αSyn pathology by disrupting Complex I function.

7-Year outcomes after surgical aortic valve replacement with a stented bovine pericardial bioprosthesis in over 1100 patients: a prospective multicenter analysis.

Objectives: Safety, efficacy, and durability are important considerations when selecting a bioprosthesis for aortic valve replacement (AVR). This study assessed 7-year clinical outcomes and haemodynamic performance of the Avalus bioprosthesis.

Methods: Patients indicated for surgical AVR were enrolled in this prospective, nonrandomized trial, conducted across 39 sites globally.

Percutaneous decannulation of extracorporeal membrane oxygenation using MANTA device: A real-world single-center experience.

Background: The MANTA vascular closure device (VCD) represents a novel approach to achieving hemostasis after large-bore femoral access procedures. Numerous clinical studies have evaluated the efficacy of the MANTA device across a range of patient populations undergoing different procedures. However, there is still a paucity of data available concerning the use of MANTA devices in aiding the decannulation of venoarterial extracorporeal membrane oxygenation (VA-ECMO).

The Role of Structured Goals of Care Discussions in Critically Ill Thoracic Surgery Patients.

The American College of Surgeons recommends structured family meetings (FM) for high-risk surgical patients. We hypothesized that goals of care discussions (GOCD) in the form of an FM, multidisciplinary family meeting (MDFM), or palliative care consult (PCC) would be underutilized in imminently dying thoracic surgery patients. A retrospective chart review at a tertiary academic medical center was performed on all inpatient mortalities and discharges to hospice after any thoracic surgery operation.

Current definitions of hemodynamic structural valve deterioration after bioprosthetic aortic valve replacement lack consistency.

Objective: New echocardiographic definitions have been proposed for hemodynamic structural valve deterioration. We aimed to study their consistency in classifying structural valve deterioration after surgical aortic valve replacement.

Methods: Data were used of patients undergoing surgical aortic valve replacement in a multicenter, prospective cohort study with a 5-year follow-up.

A person-centered approach to characterizing longitudinal ambulatory impairment in Parkinson's disease.

Loss of ambulation is common and highly variable in Parkinson's disease (PD), and poorly understood from the perspectives of those with PD. Gaining insights to the anticipated perceived trajectories and their drivers, will facilitate patient-centered care. Latent class growth analysis, a person-centered mixture modelling approach, was applied to 16,863 people with PD stratified by early (N = 8612; < 3 years), mid (N = 6181; 3-10 years) and later (N = 2070; > 10 years) disease to discern clusters with similar longitudinal patterns of self-reported walking difficulty, measured by EuroQoL 5D-5L that is validated for use in PD.

Examining the typical hemodynamic performance of nearly 3000 modern surgical aortic bioprostheses.

Objectives: The objective of this analysis was to assess the normal haemodynamic performance of contemporary surgical aortic valves at 1 year postimplant in patients undergoing surgical aortic valve replacement for significant valvular dysfunction. By pooling data from 4 multicentre studies, this study will contribute to a better understanding of the effectiveness of surgical aortic valve replacement procedures, aiding clinicians and researchers in making informed decisions regarding valve selection and patient management.

Methods: Echocardiograms were assessed by a single core laboratory.

Predictors of Functional Impairment in Bipolar Disorder: Results From 13 Cohorts From Seven Countries by the Global Bipolar Cohort Collaborative.

Objectives: Persistent functional impairment is common in bipolar disorder (BD) and is influenced by a number of demographic, clinical, and cognitive features. The goal of this project was to estimate and compare the influence of key factors on community function in multiple cohorts of well-characterized samples of individuals with BD.

Methods: Thirteen cohorts from 7 countries included = 5882 individuals with BD across multiple sites.

Effect of liraglutide on thigh muscle fat and muscle composition in adults with overweight or obesity: Results from a randomized clinical trial.

Background: Excess muscle fat is observed in obesity and associated with greater burden of cardiovascular risk factors and higher risk of mortality. Liraglutide reduces total body weight and visceral fat but its effect on muscle fat and adverse muscle composition is unknown.

Methods: This is a pre-specified secondary analysis of a randomized, double-blind, placebo-controlled trial that examined the effects of liraglutide plus a lifestyle intervention on visceral adipose tissue and ectopic fat among adults without diabetes with body mass index ≥30 kg/m or ≥27 kg/m and metabolic syndrome.

Long-term characterization of cognitive phenotypes in children with seizures over 36 months.

Rationale: Children with new-onset epilepsies often exhibit co-morbidities including cognitive dysfunction, which adversely affects academic performance. Application of unsupervised machine learning techniques has demonstrated the presence of discrete cognitive phenotypes at or near the time of diagnosis, but there is limited knowledge of their longitudinal trajectories. Here we investigate longitudinally the presence and progression of cognitive phenotypes and academic status in youth with new-onset seizures as sibling controls.

Large-scale validation of skin prion seeding activity as a biomarker for diagnosis of prion diseases.

Definitive diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) relies on the examination of brain tissues for the pathological prion protein (PrP). Our previous study revealed that PrP-seeding activity (PrP-SA) is detectable in skin of sCJD patients by an ultrasensitive PrP seed amplification assay (PrP-SAA) known as real-time quaking-induced conversion (RT-QuIC). A total of 875 skin samples were collected from 2 cohorts (1 and 2) at autopsy from 2-3 body areas of 339 cases with neuropathologically confirmed prion diseases and non-sCJD controls.

The robustness of the flow-gradient classification of severe aortic stenosis.

Objectives: A flow-gradient classification is used to determine the indication for intervention for patients with severe aortic stenosis (AS) with discordant echocardiographic parameters. We investigated the agreement in flow-gradient classification by stroke volume (SV) measurement at the left ventricular outflow tract (LVOT) and at the left ventricle.

Methods: Data were used from a prospective cohort study and patients with severe AS (aortic valve area index ≤0.

Risk Factors for Chronic Atrial Fibrillation Following Lung Lobectomy.

Introduction: Postoperative atrial fibrillation (POAF) is a common complication following lung lobectomy and is associated with increased risk of stroke, mortality, and prolonged hospital length of stay. The purpose of this study was to define the risk factors for POAF after lobectomy, hypothesizing that operative approach would be associated with risk of chronic POAF.

Methods: The TriNetX database was used to identify adult patients with no history of arrythmia receiving elective lung lobectomy for cancer from 7/6/2003-7/6/2023.

Evidence-Supported Interventions for Reducing Secondary Stroke Risk in Sub-Saharan Africa: A Systematic Review.

The study set out to perform a systematic literature review of evidence-based interventions that target the reduction of secondary stroke risk in Africa. The review analyzed longitudinal intervention studies conducted in Sub-Saharan Africa, focusing on adult participants who had suffered a prior stroke. It encompassed publications and peer-reviewed papers sourced from reputable databases, including PubMed, Ovid, Cochrane, and Web of Science.