Cardiovascular Benefits of Icosapent Ethyl in Patients With and Without Atrial Fibrillation in REDUCE-IT.

Background In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial), icosapent ethyl (IPE) versus placebo) reduced cardiovascular death, myocardial infarction, stroke, coronary revascularization, or unstable angina requiring hospitalization, but was associated with increased atrial fibrillation/atrial flutter (AF) hospitalization (3.1% IPE versus 2.1% placebo; =0.

The impact of fellowship-trained medical toxicology faculty on emergency medicine resident in-training examination scores.

Background: The American Board of Emergency Medicine (ABEM) In Training Exam (ITE) gauges residents' medical knowledge and has been shown to correlate with subsequent performance on the ABEM board qualifying examination. It is common for emergency medicine (EM) residencies to employ subspecialty-trained faculty members with the expectation of improved resident education and subspecialty knowledge. We hypothesized that the presence of subspecialty faculty in toxicology would increase residents' scores on the toxicology portion of the ITE.

Osteopontin activity modulates sex-specific calcification in engineered valve tissue mimics.

Patients with aortic valve stenosis (AVS) have sexually dimorphic phenotypes in their valve tissue, where male valvular tissue adopts a calcified phenotype and female tissue becomes more fibrotic. The molecular mechanisms that regulate sex-specific calcification in valvular tissue remain poorly understood. Here, we explored the role of osteopontin (OPN), a pro-fibrotic but anti-calcific bone sialoprotein, in regulating the calcification of female aortic valve tissue.

HDAC7 is an immunometabolic switch triaging danger signals for engagement of antimicrobial versus inflammatory responses in macrophages.

The immune system must be able to respond to a myriad of different threats, each requiring a distinct type of response. Here, we demonstrate that the cytoplasmic lysine deacetylase HDAC7 in macrophages is a metabolic switch that triages danger signals to enable the most appropriate immune response. Lipopolysaccharide (LPS) and soluble signals indicating distal or far-away danger trigger HDAC7-dependent glycolysis and proinflammatory IL-1β production.

Erratum: Health disparities and treatment approaches in portopulmonary hypertension and idiopathic pulmonary arterial hypertension: An analysis of the Pulmonary Hypertension Association Registry.

[This corrects the article DOI: 10.1177/20458940211020913.].

Cardiac Adverse Events Associated With Chemo-Radiation Versus Chemotherapy for Resectable Stage III Non-Small-Cell Lung Cancer: A Surveillance, Epidemiology and End Results-Medicare Study.

Background We compared cardiac outcomes for surgery-eligible patients with stage III non-small-cell lung cancer treated adjuvantly or neoadjuvantly with chemotherapy versus chemo-radiation therapy in the Surveillance, Epidemiology and End Results-Medicare database. Methods and Results Patients were age 66+, had stage IIIA/B resectable non-small-cell lung cancer diagnosed between 2007 and 2015, and received adjuvant or neoadjuvant chemotherapy or chemo-radiation within 121 days of diagnosis. Patients having chemo-radiation and chemotherapy only were propensity-score matched and followed from day 121 to first cardiac outcome, noncardiac death, radiation initiation by patients who received chemotherapy only, fee-for-service enrollment interruption, or December 31, 2016.

Multidisciplinary Insights into the Structure-Function Relationship of the CYP2B6 Active Site.

Cytochrome P450 2B6 (CYP2B6) is a highly polymorphic human enzyme involved in the metabolism of many clinically relevant drugs, environmental toxins, and endogenous molecules with disparate structures. Over the last 20-plus years, in silico and in vitro studies of CYP2B6 using various ligands have provided foundational information regarding the substrate specificity and structure-function relationship of this enzyme. Approaches such as homology modeling, X-ray crystallography, molecular docking, and kinetic activity assays coupled with CYP2B6 mutagenesis have done much to characterize this originally neglected monooxygenase.

Human neutrophils murine neutrophils: Does it matter?

Human and murine neutrophils differ with respect to representation in blood, receptors, nuclear morphology, signaling pathways, granule proteins, NADPH oxidase regulation, magnitude of oxidant and hypochlorous acid production, and their repertoire of secreted molecules. These differences often matter and can undermine extrapolations from murine studies to clinical care, as illustrated by several failed therapeutic interventions based on mouse models. Likewise, coevolution of host and pathogen undercuts fidelity of murine models of neutrophil-predominant human infections.

De novo variants are a common cause of genetic hearing loss.

Purpose: De novo variants (DNVs) are a well-recognized cause of genetic disorders. The contribution of DNVs to hearing loss (HL) is poorly characterized. We aimed to evaluate the rate of DNVs in HL-associated genes and assess their contribution to HL.

Extracellular matrix stiffness controls cardiac valve myofibroblast activation through epigenetic remodeling.

Aortic valve stenosis (AVS) is a progressive fibrotic disease that is caused by thickening and stiffening of valve leaflets. At the cellular level, quiescent valve interstitial cells (qVICs) activate to myofibroblasts (aVICs) that persist within the valve tissue. Given the persistence of myofibroblasts in AVS, epigenetic mechanisms have been implicated.

Patent Ductus Arteriosus: A Contemporary Perspective for the Pediatric and Adult Cardiac Care Provider.

The burden of patent ductus arteriosus (PDA) continues to be significant. In view of marked differences in preterm infants versus more mature, term counterparts (viewed on a continuum with adolescent and adult patients), mechanisms regulating ductal patency, genetic contributions, clinical consequences, and diagnostic and treatment thresholds are discussed separately, when appropriate. Among both preterm infants and older children and adults, a range of hemodynamic profiles highlighting the markedly variable consequences of the PDA are provided.

Pegcetacoplan in paroxysmal nocturnal hemoglobinuria: A systematic review on efficacy and safety.

Introduction: Pegcetacoplan, a pegylated penta-decapeptide, targets complement C3 to control both intravascular and extravascular hemolysis. This systematic review aims to study the efficacy and safety of pegcetacoplan in paroxysmal nocturnal hemoglobinuria (PNH).

Methods: We performed a comprehensive and systematic literature search for all studies on PubMed, Google Scholar, Cochrane Library, and clinicaltrials.

Thromboprophylaxis for children hospitalized with COVID-19 and MIS-C.

Background: Limited data exist about effective regimens for pharmacological thromboprophylaxis in children with acute coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C).

Objectives: Study the outcomes of institutional thromboprophylaxis protocol for primary venous thromboembolism (VTE) prevention in children hospitalized with acute COVID-19/MIS-C.

Methods: This single-center retrospective cohort study included consecutive children (aged less than 21 years) with COVID-19/MIS-C who received tailored intensity thromboprophylaxis, primarily with low-molecular-weight heparin, from April 2020 through October 2021.

The use of very low-calorie diets in subjects with obesity complicated with nonalcoholic fatty liver disease: A scoping review.

This scoping review synthesizes the existing research on the use of very low-calorie diets (VLCDs) in subjects with nonalcoholic fatty liver disease (NAFLD) and end-stage liver disease (ESLD). 19 studies were included, of which 5 were clinical trials, 11 were cohort studies, 1 was a case-control study, and 2 were case series totaling 968 subjects. About 17 studies were focused on patients with NAFLD while the two case series described in patients with ESLD on the transplant list or post-liver transplant.

microRNA-29a Regulates ADAM12 Through Direct Interaction With ADAM12 mRNA and Modulates Postischemic Perfusion Recovery.

Background Peripheral artery disease is caused by atherosclerotic occlusion of vessels outside the heart and most commonly affects vessels of the lower extremities. Angiogenesis is a part of the postischemic adaptation involved in restoring blood flow in peripheral artery disease. Previously, in a murine hind limb ischemia model of peripheral artery disease, we identified ADAM12 (a disintegrin and metalloproteinase gene 12) as a key genetic modifier of postischemic perfusion recovery.

Scylla, Charybdis, and navigating antimicrobial action in the neutrophil phagosome.

The text extracted from the initial paragraph of a paper coauthored by Zanvil Cohn, one of the pioneers in the study of leukocyte biology, highlights two phenomena that stimulated investigations of innate immunity in the middle of the last century, namely phagocytosis and intracellular antimicrobial activity. Although many features of phagocytosis have been characterized since that time, fundamental aspects of the antimicrobial action of neutrophils remain unknown. The report by Ashby et al.

Sex-Specific Differences in Endothelial Function Are Driven by Divergent Mitochondrial Ca Handling.

Background Sex-specific differences in vasodilation are mediated in part by differences in cytosolic Ca handling, but how variations in mitochondrial Ca contributes to this effect remains unknown. Here, we investigated the extent to which mitochondrial Ca entry via the MCU (mitochondrial Ca uniporter) drives sex differences in vasoreactivity in resistance arteries. Methods and Results Enhanced vasodilation of mesenteric resistance arteries to acetylcholine (ACh) was reduced to larger extent in female compared with male mice in 2 genetic models of endothelial MCU ablation.

Knockout of Sorbin And SH3 Domain Containing 2 (Sorbs2) in Cardiomyocytes Leads to Dilated Cardiomyopathy in Mice.

Background Sorbin and SH3 domain containing 2 (Sorbs2) protein is a cytoskeletal adaptor with an emerging role in cardiac biology and disease; yet, its potential relevance to adult-onset cardiomyopathies remains underexplored. Sorbs2 global knockout mice display lethal arrhythmogenic cardiomyopathy; however, the causative mechanisms remain unclear. Herein, we examine Sorbs2 dysregulation in heart failure, characterize novel Sorbs2 cardiomyocyte-specific knockout mice (Sorbs2-cKO), and explore associations between Sorbs2 genetic variations and human cardiovascular disease.