Evaluating the performance of the BOADICEA model in predicting 10-year breast cancer risks in UK Biobank.

Background: The BOADICEA model predicts breast cancer risk using cancer family history, epidemiological and genetic data. We evaluated its validity in a large prospective cohort.

Methods: We assessed model calibration, discrimination and risk classification ability in 217,885 women (6,838 incident breast cancers) aged 40-70 years old of self-reported White ethnicity with no previous cancer from the UK Biobank.

Can the Present Canadian Health Care System Provide Evidence-Based Pharmaceutical Care? Consideration of Two Important Cardiovascular Clinical Contexts.

Background: Canada is the only country with universal health care lacking universal pharmaceutical care (pharmacare). Currently, a minority portion of the population has drug coverage. Furthermore, there may be discordance between provincial plans of medications that are covered.

Tricuspid Valve S-Curves and Chamber Views: Implications for Transcatheter Tricuspid and Pulmonary Valve Interventions, Part 2 of the S-Curves and Chamber Views Series.

Despite the challenges associated with periprocedural imaging, transcatheter tricuspid valve interventions have shown important impact on outcomes. A comprehensive understanding of the anatomy of the right heart and surrounding structures is crucial. One way to optimize these interventions is by identifying the optimal fluoroscopic viewing angles along the S-curve of the tricuspid valve.

ATP citrate lyase drives vascular remodeling in systemic and pulmonary vascular diseases through metabolic and epigenetic changes.

ATP citrate lyase (ACLY), a crucial enzyme in de novo lipid synthesis and histone acetylation, plays a key role in regulating vascular smooth muscle cell (VSMC) proliferation and survival. We found that human coronary and pulmonary artery tissues had up-regulated ACLY expression during vascular remodeling in coronary artery disease and pulmonary arterial hypertension. Pharmacological and genetic inhibition of ACLY in human primary cultured VSMCs isolated from the coronary arteries of patients with coronary artery diseases and from the distal pulmonary arteries of patients with pulmonary arterial hypertension resulted in reduced cellular proliferation and migration and increased susceptibility to apoptosis.

Cost-effectiveness analysis of radiofrequency renal denervation for uncontrolled hypertension in Canada.

Aims: Catheter-based radiofrequency renal denervation (RF RDN) is an interventional treatment for uncontrolled hypertension. This analysis explored the therapy's lifetime cost-effectiveness in a Canadian healthcare setting.

Materials And Methods: A decision-analytic Markov model was used to project health events, costs, and quality-adjusted life years over a lifetime horizon.

An overview of drug-induced sodium channel blockade and changes in cardiac conduction: Implications for drug safety.

The human voltage-gated sodium channel Na1.5 (hNa1.5/SCN5A) plays a critical role in the initiation and propagation of action potentials in cardiac myocytes, and its modulation by various drugs has significant implications for cardiac safety.

Baseline Characteristics of Dupilumab-Treated Patients with Asthma in the Real World: The RAPID Global Registry.

Introduction: Patients with uncontrolled, moderate-to-severe asthma have a higher risk for exacerbations, negatively impacting lung function and quality of life. Dupilumab, a fully human monoclonal antibody, blocks interleukins 4 and 13, key and central drivers of type 2 inflammation. Dupilumab has been effective in the treatment of certain types of moderate-to-severe asthma across several clinical trials.

Impact of intensive versus nonintensive antithrombotic treatment on device-related thrombus after left atrial appendage closure.

Introduction And Objectives: The optimal antithrombotic therapy (AT) after left atrial appendage closure (LAAC) is debated. We assessed the impact of intensive vs nonintensive AT on the incidence of device-related thrombus (DRT) based on whether the device implantation was classified as optimal or suboptimal.

Methods: This study included patients who underwent successful LAAC in 9 centers.

Aortic Valve Replacement vs Clinical Surveillance in Asymptomatic Severe Aortic Stenosis: A Systematic Review and Meta-Analysis.

Background: Current guidelines recommend a strategy of clinical surveillance (CS) for patients with asymptomatic severe aortic stenosis (AS) and a normal left ventricular ejection fraction.

Objectives: The aim of this study was to conduct a study-level meta-analysis of randomized controlled trials (RCTs) evaluating the effect of early aortic valve replacement (AVR) compared with CS in patients with asymptomatic severe AS.

Methods: Studies were quantitatively assessed in a meta-analysis using random-effects modeling.

Erratum: Burden of disease attributable to high body mass index: an analysis of data from the Global Burden of Disease Study 2021.

[This corrects the article DOI: 10.1016/j.eclinm.

Extreme LDL-C concentration is associated with increased cardiovascular disease in women with homozygous familial hypercholesterolemia.

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disease of low-density lipoprotein cholesterol (LDL-C) metabolism. Despite the devastating effect of this disease on atherosclerotic cardiovascular health, the disease phenotype and severity are more heterogeneous than previously thought. The predictors of atherosclerotic cardiovascular disease (ASCVD) in HoFH patients have never been systematically studied.

Can transcranial direct current stimulation (tDCS) over the motor cortex increase endurance running performance? a randomized crossover-controlled trial.

Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, has been shown to increase exercise performance in strength and cycling studies but its effects on running endurance remain unclear. The objectives of this randomized sham-controlled crossover trial were to assess tDCS efficacy on submaximal treadmill running time to exhaustion (TTE). Forty-five healthy male runners aged between 18 and 32 years (mean maximal oxygen consumption: 46.

Impact of a national dementia research consortium: The Canadian Consortium on Neurodegeneration in Aging (CCNA).

The Canadian Consortium on Neurodegeneration in Aging (CCNA) was created by the Canadian federal government through its health research funding agency, the Canadian Institutes for Health Research (CIHR), in 2014, as a response to the G7 initiative to fight dementia. Two five-year funding cycles (2014-2019; 2019-2024) have occurred following peer review, and a third cycle (Phase 3) has just begun. A unique construct was mandated, consisting of 20 national teams in Phase I and 19 teams in Phase II (with research topics spanning from basic to clinical science to health resource systems) along with cross-cutting programs to support them.

Diverse NKT cells regulate early inflammation and neurological outcomes after cardiac arrest and resuscitation.

Neurological injury drives most deaths and morbidity among patients hospitalized for out-of-hospital cardiac arrest (OHCA). Despite its clinical importance, there are no effective pharmacological therapies targeting post-cardiac arrest (CA) neurological injury. Here, we analyzed circulating immune cells from a large cohort of patients with OHCA, finding that lymphopenia independently associated with poor neurological outcomes.

Targeting proprotein convertase subtilisin/kexin type 7 in macrophages as a therapeutic strategy to mitigate myocardial infarction-induced inflammation.

Myocardial infarction (MI), a major form of coronary artery disease (CAD), triggers a severe inflammatory response in the heart, resulting in increased cell death and adverse ventricular remodeling. Despite treatment advancements, MI remains a significant risk factor for heart failure, underscoring the necessity for a more in-depth exploration of immune cell mechanisms. Proprotein convertase subtilisin/kexin type 7 (PCSK7), expressed in various tissues and immune cells, has been implicated in cardiovascular disease, yet its specific role in cardiac immune cells remains poorly understood.