Benefits of the Non-Steroidal Mineralocorticoid Receptor Antagonist Finerenone in Metabolic Syndrome-Related Heart Failure with Preserved Ejection Fraction.

The mineralocorticoid receptor (MR) plays an important role in the development of chronic kidney disease (CKD) and associated cardiovascular complications. Antagonizing the overactivation of the MR with MR antagonists (MRA) is a therapeutic option, but their use in patients with CKD is limited due to the associated risk of hyperkalemia. Finerenone is a non-steroidal MRA associated with an improved benefit-risk profile in comparison to steroidal MRAs.

Associations of childhood adiposity with adult intima-media thickness and inflammation: a 20-year longitudinal population-based cohort.

Background: The associations between childhood adiposity and adult increased carotid intima-media thickness (cIMT) have been well established, which might be corroborated by the association between adiposity in children and inflammation in adults. However, longitudinal data regarding biological pathways associated with childhood adiposity are lacking.

Methods: The current study included participants from the STANISLAS cohort who had adiposity measurements at age 5-18 years [ N  = 519, mean (SD) age, 13.

Improving representativeness in trials: a call to action from the Global Cardiovascular Clinical Trialists Forum.

Participants enrolled in cardiovascular disease (CVD) randomized controlled trials are not often representative of the population living with the disease. Older adults, children, women, Black, Indigenous and People of Color, and people living in low- and middle-income countries are typically under-enrolled in trials relative to disease distribution. Treatment effect estimates of CVD therapies have been largely derived from trial evidence generated in White men without complex comorbidities, limiting the generalizability of evidence.

Implementation of a centralized pharmacovigilance system in academic pan-European clinical trials: Experience from EU-Response and conect4children consortia.

Setting-up a high quality, compliant and efficient pharmacovigilance (PV) system in multi-country clinical trials can be more challenging for academic sponsors than for companies. To ensure the safety of all participants in academic studies and that the PV system fulfils all regulations, we set up a centralized PV system that allows sponsors to delegate work on PV. This initiative was put in practice by our Inserm-ANRS MIE PV department in two distinct multinational European consortia with 19 participating countries: conect4children (c4c) for paediatrics research and EU-Response for Covid-19 platform trials.

Aetiology, clinical features, diagnostic studies, and outcomes of community-acquired pneumonia in kidney transplant recipients admitted to hospital: a multicentre retrospective French cohort study.

Objectives: To assess the aetiology, clinical features, diagnostic studies and outcomes of community-acquired pneumonia (CAP) in a French cohort of hospitalized kidney transplant recipients.

Methods: We performed a retrospective, multicentre study in kidney transplant recipients admitted to ten French centres for CAP from January 2016 to December 2018. CAP discharge diagnoses were clinically and radiologically validated.

Paediatric drug development and evaluation: Existing challenges and recommendations.

Despite various international regulatory initiatives over the last 20 years, many challenges remain in the field of paediatric drug development and evaluation. Indeed, drug research and development is still focused essentially on adult indications, thereby excluding many paediatric patients, limiting the feasibility of trials and favouring competing developments. Off-label prescribing persists and the development of age-appropriate dosage forms for children remains limited.

Randomized Trial of Vaccines for Zaire Ebola Virus Disease.

Background: Questions remain concerning the rapidity of immune responses and the durability and safety of vaccines used to prevent Zaire Ebola virus disease.

Methods: We conducted two randomized, placebo-controlled trials - one involving adults and one involving children - to evaluate the safety and immune responses of three vaccine regimens against Zaire Ebola virus disease: Ad26.ZEBOV followed by MVA-BN-Filo 56 days later (the Ad26-MVA group), rVSVΔG-ZEBOV-GP followed by placebo 56 days later (the rVSV group), and rVSVΔG-ZEBOV-GP followed by rVSVΔG-ZEBOV-GP 56 days later (the rVSV-booster group).

Sex-dependent expression of neutrophil gelatinase-associated lipocalin in aortic stenosis.

Background: Accumulating evidence suggest the existence of sex-related differences in the pathogenesis of aortic stenosis (AS) with inflammation, oxidative stress, fibrosis and calcification being over-represented in men. Neutrophil gelatinase-associated lipocalin (NGAL) is expressed in a myriad of tissues and cell types, and it is associated with acute and chronic pathological processes comprising inflammation, fibrosis or calcification. Sex-dependent signatures have been evidenced for NGAL which expression has been associated predominantly in males to metabolic and cardiovascular disorders.

Effect of adaptive servo-ventilation for central sleep apnoea in systolic heart failure on muscle sympathetic nerve activity: a SERVE-HF randomised ancillary study.

Background: Adaptive servo-ventilation (ASV) effectively suppresses central sleep apnoea (CSA) but has been associated with increased all-cause and cardiovascular mortality in chronic heart failure patients with reduced ventricular ejection fraction (HFrEF). All-cause and, especially, cardiovascular mortality in chronic heart failure is highly correlated with sympathetic tone. This analysis of SERVE-HF data investigated the effect of ASV on sympathetic tone in patients with HFrEF and CSA.

Development of an international standard set of outcome measures for patients with venous thromboembolism: an International Consortium for Health Outcomes Measurement consensus recommendation.

The International Consortium for Health Outcomes Measurement assembled an international working group of venous thromboembolism experts and patient representatives to develop a standardised minimum set of outcomes and outcome measurements for integration into clinical practice and potentially research to support clinical decision making and benchmarking of quality of care. 15 core outcomes important to patients and health-care professionals were selected and categorised into four domains: patient-reported outcomes, long term consequences of the disease, disease-specific complications, and treatment-related complications. The outcomes and outcome measures were designed to apply to all patients with venous thromboembolism aged 16 years or older.

A national platform for Covid-19 vaccine studies recruitment in France: Covireivac volunteer's characteristics.

During the Covid-19 pandemic, the urgent need for safe and effective vaccines has led to many vaccine trials, implying fast and extensive recruitment of volunteers. In France, until 2020, vaccine clinical research participants were usually recruited locally, through center-based pools of volunteers, and local communication plans. Covireivac is a French public online platform launched on 10/01/2020 that enables national, large-scale recruitment of volunteers for Covid-19 vaccine studies.

Trial of Cinpanemab in Early Parkinson's Disease.

Background: Aggregated α-synuclein plays an important role in Parkinson's disease pathogenesis. Cinpanemab, a human-derived monoclonal antibody that binds to α-synuclein, is being evaluated as a disease-modifying treatment for Parkinson's disease.

Methods: In a 52-week, multicenter, double-blind, phase 2 trial, we randomly assigned, in a 2:1:2:2 ratio, participants with early Parkinson's disease to receive intravenous infusions of placebo (control) or cinpanemab at a dose of 250 mg, 1250 mg, or 3500 mg every 4 weeks, followed by an active-treatment dose-blinded extension period for up to 112 weeks.

Impact of early mean arterial pressure level on severe acute kidney injury occurrence after out-of-hospital cardiac arrest.

Background: The optimal early mean arterial pressure (MAP) level in terms of renal function remains to be established in patients with out-of-hospital cardiac arrest (OHCA). We aimed to evaluate the association between early MAP level and severe acute kidney injury (AKI) occurrence in patients with OHCA.

Results: In 568 consecutive patients, the percentage time spent below a predefined MAP threshold and the corresponding area below threshold (ABT) were calculated from continuous MAP measurement.

Optimizing the Design and Analysis of Future AKI Trials.

AKI is a complex clinical syndrome associated with an increased risk of morbidity and mortality, particularly in critically ill and perioperative patient populations. Most AKI clinical trials have been inconclusive, failing to detect clinically important treatment effects at predetermined statistical thresholds. Heterogeneity in the pathobiology, etiology, presentation, and clinical course of AKI remains a key challenge in successfully testing new approaches for AKI prevention and treatment.

The non-steroidal mineralocorticoid receptor antagonist finerenone is a novel therapeutic option for patients with Type 2 diabetes and chronic kidney disease.

Despite strong preclinical data supporting the use of mineralocorticoid receptor antagonists (MRAs) to provide cardiorenal protection in rodent models of diabetes, the clinical evidence of their utility in treating chronic kidney disease (CKD) has been limited. Two major clinical trials (FIDELIO-DKD and FIGARO-DKD) including more than 13,000 patients with albuminuric CKD and Type 2 diabetes randomized to placebo or finerenone (MRA) have recently provided exciting results showing a significant risk reduction for kidney and cardiovascular outcomes. In this review, we will summarize the major findings of these trials, together with post-hoc and pooled analyses that have allowed evaluation of the efficacy and safety of finerenone across the spectrum of CKD, revealing significant protective effects of finerenone against kidney failure, new-onset atrial fibrillation or flutter, new-onset heart failure, cardiovascular death, and first and total heart-failure hospitalizations.

Biglycan Is a Novel Mineralocorticoid Receptor Target Involved in Aldosterone/Salt-Induced Glomerular Injury.

The beneficial effects of mineralocorticoid receptor (MR) antagonists (MRAs) for various kidney diseases are established. However, the underlying mechanisms of kidney injury induced by MR activation remain to be elucidated. We recently reported aldosterone-induced enhancement of proteoglycan expression in mitral valve interstitial cells and its association with fibromyxomatous valvular disorder.

Prognostic significance of severe coronary microvascular dysfunction post-PCI in patients with STEMI: A systematic review and meta-analysis.

Coronary microvascular dysfunction (CMVD) is common and associated with poorer outcomes in patients with ST Segment Elevation Myocardial Infarction (STEMI). The index of microcirculatory resistance (IMR) and the index of hyperemic microvascular resistance (HMR) are both invasive indexes of microvascular resistance proposed for the diagnosis of severe CMVD after primary percutaneous coronary intervention (pPCI). However, these indexes are not routinely assessed in STEMI patients.