Health Expenditures of Patients With Diabetes After Bariatric Surgery: Comparing Gastric Bypass and Sleeve Gastrectomy.

Background: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) differ in their effects on body weight and risk for reoperation. However, it is unclear whether long-term health expenditures differ by procedure type in patients with diabetes.

Objective: To compare health expenditures 3 years before and 5.

Design and early progress of the Comparison of Anticoagulation and anti-Platelet Therapies for Intracranial Vascular Atherostenosis (CAPTIVA) trial.

Background: The usual antithrombotic treatment for symptomatic intracranial atherosclerotic stenosis (ICAS) consists of dual treatment with clopidogrel and aspirin for 90 days followed by aspirin alone but the risk of recurrent stroke remains high up to 12 months. The Comparison of Anticoagulation and anti-Platelet Therapies for Intracranial Vascular Atherostenosis (CAPTIVA) trial was designed to determine whether other combinations of dual antithrombotic therapy are superior to clopidogrel and aspirin.

Methods: CAPTIVA is an ongoing, prospective, double-blinded, three-arm clinical trial at over 100 sites in the United States and Canada that will randomize 1683 high-risk subjects with a symptomatic infarct attributed to 70-99% stenosis of a major intracranial artery to 12 months of treatment with (1) ticagrelor (180 mg loading dose, then 90 mg twice daily), (2) low-dose rivaroxaban (2.

Effect of Characteristic Inflammatory and Structural Pelvic Magnetic Resonance Imaging Lesions on Expert Assessment of Axial Juvenile Spondyloarthritis.

Objective: To evaluate the influence of pelvic magnetic resonance imaging (MRI) findings on axial disease assessment in juvenile spondyloarthritis (JSpA).

Methods: This was a cross-sectional study of patients with JSpA with suspected axial disease. Three experts reviewed each case and rated their confidence (-3 to +3) in the presence of axial disease, first with clinical data and second with clinical and MRI data.

Repurposing Licensed Drugs with Activity Against Epstein-Barr Virus for Treatment of Multiple Sclerosis: A Systematic Approach.

Background: Epstein-Barr virus (EBV) is implicated as a necessary factor in the development of multiple sclerosis (MS) and may also be a driver of disease activity. Although it is not clear whether ongoing viral replication is the driver for MS pathology, MS researchers have considered the prospect of using drugs with potential efficacy against EBV in the treatment of MS. We have undertaken scientific and lived experience expert panel reviews to shortlist existing licensed therapies that could be used in later-stage clinical trials in MS.

One-quarter of freshwater fauna threatened with extinction.

Freshwater ecosystems are highly biodiverse and important for livelihoods and economic development, but are under substantial stress. To date, comprehensive global assessments of extinction risk have not included any speciose groups primarily living in freshwaters. Consequently, data from predominantly terrestrial tetrapods are used to guide environmental policy and conservation prioritization, whereas recent proposals for target setting in freshwaters use abiotic factors.

A Global Collaborative Comparison of SARS-CoV-2 Antigenicity Across 15 Laboratories.

Setting up a global SARS-CoV-2 surveillance system requires an understanding of how virus isolation and propagation practices, use of animal or human sera, and different neutralisation assay platforms influence assessment of SARS-CoV-2 antigenicity. In this study, with the contribution of 15 independent laboratories across all WHO regions, we carried out a controlled analysis of neutralisation assay platforms using the first WHO International Standard for antibodies to SARS-CoV-2 variants of concern (source: NIBSC). Live virus isolates (source: WHO BioHub or individual labs) or spike plasmids (individual labs) for pseudovirus production were used to perform neutralisation assays using the same serum panels.

snRNA-seq stratifies multiple sclerosis patients into distinct white matter glial responses.

Poor understanding of the cellular and molecular basis of clinical and genetic heterogeneity in progressive multiple sclerosis (MS) has hindered the search for new effective therapies. To address this gap, we analyzed 632,000 single-nucleus RNA sequencing profiles from 156 brain tissue samples of MS and control donors to examine inter- and intra-donor heterogeneity. We found distinct cell type-specific gene expression changes between MS gray and white matter, highlighting clear pathology differences.

Lived Experience of Patients and Caregivers in Rare Genetic Neurological Gene Therapy Clinical Trials in Children.

To date, sparse attention has been paid to the importance of the "lived experience" of participants and their caregivers in pediatric gene therapy (GT) trials for rare genetic neurological disorders. Pediatric GT studies differ meaningfully from adult GT studies as the decision to participate involves a dyad: the child participant and their caregiver(s). As a multistakeholder group of authors, we are a diverse group with expert perspectives on the social, emotional, physical, and logistical burdens/benefits of trial participation and the myriad ways they affect pediatric GT research.

Reporting of pre-existing multiple long-term conditions in physical rehabilitation for long COVID: a scoping review.

Background: Physical rehabilitation may improve health and wellbeing outcomes for some adults living with long COVID. However, individuals living with pre-existing multiple long-term conditions (MLTCs) and long COVID may have additional rehabilitation challenges. This scoping review aims to identify the available evidence describing physical rehabilitation interventions for adults living with long COVID, to systematically map the reporting of pre-existing MLTCs, and to describe the characteristics of physical rehabilitation interventions used in adults with both pre-existing long-term conditions (LTCs) and long COVID.

Outcomes of Community-Acquired Acute Kidney Injury: A Cohort Study of US Veterans.

Background: Community-acquired acute kidney injury (CA-AKI) occurs outside of the hospital and is the most common form of AKI. CA-AKI is not well understood, which hinders efforts to prevent, identify, and manage CA-AKI.

Objective: Examine 30-day outcomes following CA-AKI using national administrative and lab data from the Veterans Health Administration (VA).

Microvascular Inflammation of Kidney Allografts and Clinical Outcomes.

Background: The heterogeneous clinical presentation of graft microvascular inflammation poses a major challenge to successful kidney transplantation. The effect of microvascular inflammation on allograft outcomes is unclear.

Methods: We conducted a cohort study that included kidney-transplant recipients from more than 30 transplantation centers in Europe and North America who had undergone allograft biopsy between 2004 and 2023.

Graduating vascular surgery trainee proficiency in endovascular and open peripheral revascularization procedures.

Background: Endovascular interventions for peripheral artery disease have increased in prevalence over time given the inherent benefits of minimally invasive approaches. Although it is essential that vascular surgery graduates are facile with endovascular techniques, the results of the BEST-CLI (Best Endovascular vs. Best Surgical Therapy in Patients With Critical Limb Ischemia) trial highlight the equivalent importance of ensuring trainee competence in open skills.

Disease prediction with multi-omics and biomarkers empowers case-control genetic discoveries in the UK Biobank.

The emergence of biobank-level datasets offers new opportunities to discover novel biomarkers and develop predictive algorithms for human disease. Here, we present an ensemble machine-learning framework (machine learning with phenotype associations, MILTON) utilizing a range of biomarkers to predict 3,213 diseases in the UK Biobank. Leveraging the UK Biobank's longitudinal health record data, MILTON predicts incident disease cases undiagnosed at time of recruitment, largely outperforming available polygenic risk scores.

Persistent Autonomic and Immunologic Abnormalities in Neurologic Post-Acute Sequelae of SARS-CoV2 Infection.

Objectives: After acute coronavirus disease-2019 (COVID-19), people often experience fatigue, "brain fog," or other central neurologic symptoms (neuro-post-acute SARS-CoV2, or "Neuro-PASC"). In this observational study we evaluated whether abnormalities noted on initial evaluation persist after at least another year.

Methods: Neuro-PASC research participants who had undergone comprehensive inpatient testing at the NIH Clinical Center returned after at least 1 year for follow-up assessments including symptoms rating scales, MRI, lumbar puncture for tests of the CSF, physiologic recordings during the Valsalva maneuver and head-up tilting (with serial plasma catechols and cardiac Doppler ultrasound during the tilting), blood volume measurement, skin biopsies to examine sympathetic innervation, and blood sampling for neuroendocrine and immunologic measures.

Nipocalimab in Early-Onset Severe Hemolytic Disease of the Fetus and Newborn.

Background: In early-onset severe hemolytic disease of the fetus and newborn (HDFN), transplacental transfer of maternal antierythrocyte IgG alloantibodies causes fetal anemia that leads to the use of high-risk intrauterine transfusions in order to avoid fetal hydrops and fetal death. Nipocalimab, an anti-neonatal Fc receptor blocker, inhibits transplacental IgG transfer and lowers maternal IgG levels.

Methods: In an international, open-label, single-group, phase 2 study, we assessed treatment with intravenous nipocalimab (30 or 45 mg per kilogram of body weight per week) administered from 14 to 35 weeks' gestation in participants with pregnancies at high risk for recurrent early-onset severe HDFN.

The cytokine Meteorin-like inhibits anti-tumor CD8 T cell responses by disrupting mitochondrial function.

Tumor-infiltrating lymphocyte (TIL) hypofunction contributes to the progression of advanced cancers and is a frequent target of immunotherapy. Emerging evidence indicates that metabolic insufficiency drives T cell hypofunction during tonic stimulation, but the signals that initiate metabolic reprogramming in this context are largely unknown. Here, we found that Meteorin-like (METRNL), a metabolically active cytokine secreted by immune cells in the tumor microenvironment (TME), induced bioenergetic failure of CD8 T cells.

Distal Ventricular Pacing for Drug-Refractory Mid-Cavity Obstructive Hypertrophic Cardiomyopathy: A Randomized, Placebo-Controlled Trial of Personalized Pacing.

Background: Patients with refractory, symptomatic left ventricular (LV) mid-cavity obstructive (LVMCO) hypertrophic cardiomyopathy have few therapeutic options. Right ventricular pacing is associated with modest hemodynamic and symptomatic improvement, and LV pacing pilot data suggest therapeutic potential. We hypothesized that site-specific pacing would reduce LVMCO gradients and improve symptoms.

Inhibition of Renin Expression Is Regulated by an Epigenetic Switch From an Active to a Poised State.

Background: Renin-expressing cells are myoendocrine cells crucial for the maintenance of homeostasis. Renin is regulated by cAMP, p300 (histone acetyltransferase p300)/CBP (CREB-binding protein), and Brd4 (bromodomain-containing protein 4) proteins and associated pathways. However, the specific regulatory changes that occur following inhibition of these pathways are not clear.