Real-World Treatment Patterns After Discontinuation of Venetoclax or BTKis in the Frontline Setting Among Older Adults With Chronic Lymphocytic Leukemia.

Purpose: Venetoclax and Bruton's tyrosine kinase inhibitors (BTKis) are key treatment options for patients with chronic lymphocytic leukemia (CLL) in the frontline setting. This study characterized postdiscontinuation treatment patterns and hospitalization of frontline venetoclax and BTKis in a national sample of older adults with CLL.

Methods: We identified 1,770 Medicare beneficiaries 66 years and older with CLL initiating venetoclax with obinutuzumab (VEN-O, n = 193) or BTKi treatment (n = 1,577) in the frontline setting between June 01, 2019, and June 30, 2020.

A genetically encoded actuator boosts L-type calcium channel function in diverse physiological settings.

L-type Ca channels (Ca1.2/1.3) convey influx of calcium ions that orchestrate a bevy of biological responses including muscle contraction, neuronal function, and gene transcription.

A Genetically Encoded Actuator Selectively Boosts L-type Calcium Channels in Diverse Physiological Settings.

L-type Ca channels (Ca 1.2/1.3) convey influx of calcium ions (Ca ) that orchestrate a bevy of biological responses including muscle contraction and gene transcription.

Real-World Effectiveness of 8-Week Glecaprevir/Pibrentasvir in Treatment-Naïve, Compensated Cirrhotic HCV Patients.

Introduction: The EXPEDITION-8 clinical trial has demonstrated that treatment-naïve patients with compensated cirrhosis (TN/CC) of HCV genotypes 1-6 can achieve a 98% intent-to-treat sustained virologic response rate 12 weeks post-treatment with an 8-week glecaprevir/pibrentasvir (G/P) regimen. Further real-world evidence is needed to support the effectiveness of 8-week G/P in a clinical practice setting and to consolidate these treatment recommendations. The aim of this study is to contribute real-world evidence for the effectiveness of an 8-week G/P treatment in TN/CC patients with HCV genotypes 1-6.

Shorter Duration Hepatitis C Virus Treatment is Associated with Better Persistence to Prescription Refills in People Who Inject Drugs: A Real-World Study.

Introduction: Direct-acting antiviral (DAA) therapy is highly effective in curing hepatitis C virus (HCV) infection in people who inject drugs (PWID). Previous studies showed declining persistence to DAA therapy over the course of treatment. This study compares real-world medication persistence to prescription refills for 8- versus 12-week DAA in treatment-naïve PWID with chronic HCV with compensated cirrhosis or without cirrhosis.

Engineered cardiac tissue model of restrictive cardiomyopathy for drug discovery.

Restrictive cardiomyopathy (RCM) is defined as increased myocardial stiffness and impaired diastolic relaxation leading to elevated ventricular filling pressures. Human variants in filamin C (FLNC) are linked to a variety of cardiomyopathies, and in this study, we investigate an in-frame deletion (c.7416_7418delGAA, p.

Five-Year Follow-up after Transcatheter Repair of Secondary Mitral Regurgitation.

Background: Data from a 5-year follow-up of outcomes after transcatheter edge-to-edge repair of severe mitral regurgitation, as compared with outcomes after maximal doses of guideline-directed medical therapy alone, in patients with heart failure are now available.

Methods: We randomly assigned patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy to undergo transcatheter edge-to-edge repair plus receive medical therapy (device group) or to receive medical therapy alone (control group) at 78 sites in the United States and Canada. The primary effectiveness end point was all hospitalizations for heart failure through 2 years of follow-up.

Sympathetic Nervous System Regulation of Cardiac Calcium Channels.

Calcium influx through voltage-gated calcium channels, Ca1.2, in cardiomyocytes initiates excitation-contraction coupling in the heart. The force and rate of cardiac contraction are modulated by the sympathetic nervous system, mediated substantially by changes in intracellular calcium.

Bleeding and Ischemic Outcomes With Ticagrelor Monotherapy According to Body Mass Index.

Background: There is a paucity of data regarding the safety and efficacy of different antiplatelet regimens according to standardized body mass index (BMI) categories.

Objectives: The aim of this study was to investigate bleeding and ischemic outcomes according to BMI in the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial.

Methods: The TWILIGHT trial randomized high-risk patients to ticagrelor plus aspirin or ticagrelor plus placebo at 3 months after percutaneous coronary intervention.

Ticagrelor with and without aspirin in patients with a prior coronary artery bypass graft undergoing percutaneous coronary intervention: the TWILIGHT-CABG study.

Background: Prior coronary artery bypass graft surgery (CABG) patients undergoing percutaneous coronary intervention (PCI) are often older and present with multiple comorbidities. Ticagrelor monotherapy after a short course of dual antiplatelet therapy (DAPT) has emerged as an effective bleeding-avoidance strategy among high-risk patients.

Aims: We aimed to examine the effects of ticagrelor with or without aspirin in prior CABG patients undergoing PCI within the TWILIGHT trial.

Polymer-Based Versus Polymer-Free Stents in High Bleeding Risk Patients: Final 2-Year Results From Onyx ONE.

Background: Resolute Onyx polymer-based zotarolimus-eluting stents (ZES) were noninferior in safety and effectiveness to BioFreedom polymer-free biolimus A9-coated stents (DCS) in high-bleeding-risk (HBR) patients treated with 1-month dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy (SAPT) at 1 year.

Objectives: This study reports the final 2-year results of the randomized Onyx ONE trial.

Methods: The Onyx ONE (A Randomized Controlled Trial With Resolute Onyx in One Month Dual Antiplatelet Therapy (DAPT) for High-Bleeding Risk Patients) trial randomly assigned HBR patients to treatment with ZES or DCS.

Fibroblast growth factor homologous factors serve as a molecular rheostat in tuning arrhythmogenic cardiac late sodium current.

Voltage-gated sodium (Nav1.5) channels support the genesis and brisk spatial propagation of action potentials in the heart. Disruption of Na1.

Increased Ca2+ influx through CaV1.2 drives aortic valve calcification.

Calcific aortic valve disease (CAVD) is heritable, as revealed by recent GWAS. While polymorphisms linked to increased expression of CACNA1C - encoding the CaV1.2 L-type voltage-gated Ca2+ channel - and increased Ca2+ signaling are associated with CAVD, whether increased Ca2+ influx through the druggable CaV1.

Detecting Cardiovascular Protein-Protein Interactions by Proximity Proteomics.

Rapidly changing and transient protein-protein interactions regulate dynamic cellular processes in the cardiovascular system. Traditional methods, including affinity purification and mass spectrometry, have revealed many macromolecular complexes in cardiomyocytes and the vasculature. Yet these methods often fail to identify in vivo or transient protein-protein interactions.

Awareness and Epidemiology of Chronic Hepatitis C Virus Infections in Florida.

Introduction: Progress towards achieving hepatitis C virus (HCV) elimination in Florida has been hampered by barriers to screening, linkage to care, and treatment. This study aims to describe the HCV care cascade and patient characteristics in Florida.

Methods: This analysis combined HCV-related laboratory data and patient characteristics from two, large US laboratory datasets that included individuals tested for HCV antibody (Ab) and HCV ribonucleic acid (RNA) viral load between January 2015 and December 2019.

Adrenergic Regulation of Calcium Channels in the Heart.

Each heartbeat is initiated by the action potential, an electrical signal that depolarizes the plasma membrane and activates a cycle of calcium influx via voltage-gated calcium channels, calcium release via ryanodine receptors, and calcium reuptake and efflux via calcium-ATPase pumps and sodium-calcium exchangers. Agonists of the sympathetic nervous system bind to adrenergic receptors in cardiomyocytes, which, via cascading signal transduction pathways and protein kinase A (PKA), increase the heart rate (chronotropy), the strength of myocardial contraction (inotropy), and the rate of myocardial relaxation (lusitropy). These effects correlate with increased intracellular concentration of calcium, which is required for the augmentation of cardiomyocyte contraction.

Attenuating persistent sodium current-induced atrial myopathy and fibrillation by preventing mitochondrial oxidative stress.

Mechanistically driven therapies for atrial fibrillation (AF), the most common cardiac arrhythmia, are urgently needed, the development of which requires improved understanding of the cellular signaling pathways that facilitate the structural and electrophysiological remodeling that occurs in the atria. Similar to humans, increased persistent Na+ current leads to the development of an atrial myopathy and spontaneous and long-lasting episodes of AF in mice. How increased persistent Na+ current causes both structural and electrophysiological remodeling in the atria is unknown.