Validation of the Valve Academic Research Consortium High Bleeding Risk Definition in Patients Undergoing TAVR.

Background: The Valve Academic Research Consortium for High Bleeding Risk (VARC-HBR) has recently introduced a consensus document that outlines risk factors to identify high bleeding risk in patients undergoing transcatheter aortic valve replacement. The objective of the present study was to evaluate the prevalence and predictive value of the VARC-HBR definition in a contemporary, large-scale transcatheter aortic valve replacement population.

Methods: Multicenter study including 10 449 patients undergoing transcatheter aortic valve replacement.

Trastuzumab Deruxtecan in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Gastric Cancer in a Real-World Setting: A Nationwide Cohort Study.

Introduction: Trastuzumab deruxtecan (T-DXd) has been approved for human epidermal growth factor receptor 2-positive locally advanced or metastatic gastric and gastroesophageal junction (HER2+ mG/GEJ) cancer since July 2022 in France, through an accelerated approval. The aim of this study was to evaluate its real-world use.

Methods: We characterized T-DXd users treated for HER2+ mG/GEJ cancer using data from the French National Health Insurance database.

Artificial intelligence-based electrocardiogram analysis improves atrial arrhythmia detection from a smartwatch electrocardiogram.

Aims: Smartwatch electrocardiograms (SW ECGs) have been identified as a non-invasive solution to assess abnormal heart rhythm, especially atrial arrhythmias (AAs) that are related to stroke risk. However, the performance of these tools is limited and could be improved with the use of deep neural network (DNN) algorithms, particularly for specific populations encountered in clinical cardiology practice.

Methods And Results: A total of 400 patients from the electrophysiology department of one tertiary care hospital were included in two similar clinical trials (respectively, 200 patients per study).

Clinical outcomes with thin versus thick strut polymer-free biolimus-coated stents at 3 years.

Background: For high bleeding-risk patients (HBR) undergoing percutaneous coronary intervention (PCI), the LEADERS FREE (LF) and LEADERS FREE II (LF II) trials established the safety and efficacy of a stainless steel polymer-free biolimus-coated stent (SS-BCS) with 30 days of dual antiplatelet treatment (DAPT). The LEADERS FREE III (LF III) trial investigated clinical outcomes after PCI with the next-generation cobalt-chromium thin-strut polymer-free biolimus-coated stent (CoCr-BCS) in HBR patients.

Aims: To report the final 3-year results of the LF III trial and compare them to LF II.

Risk Burden of Cancer in Patients Treated With Abbreviated Dual Antiplatelet Therapy After PCI: Analysis of Multicenter Controlled High-Bleeding Risk Trials.

Background: Oncological patients with coronary artery disease face an elevated risk of hemorrhagic and ischemic events following percutaneous coronary intervention. Despite medical guidelines recommending minimal dual antiplatelet therapy (DAPT) duration for patients with cancer, dedicated data on abbreviated DAPT in this population is lacking. This study aims to evaluate the occurrence of ischemic and hemorrhagic events in patients with cancer compared with other high-bleeding risk individuals.

Reductions in World Health Organization risk drinking level are associated with improvements in sleep problems among individuals with alcohol use disorder.

Aims: Among individuals with alcohol use disorder (AUD), sleep disturbances are pervasive and contribute to the etiology and maintenance of AUD. However, despite increased attention toward the relationship between alcohol use and sleep, limited empirical research has systematically examined whether reductions in drinking during treatment for AUD are associated with improvements in sleep problems.

Methods: We used data from a multisite, randomized, controlled trial that compared 6 months of treatment with gabapentin enacarbil extended-release with placebo for adults with moderate-to-severe AUD (N = 346).

Redo-TAVI with the ACURATE neo2 and Prime XL for balloon-expandable transcatheter heart valve failure.

Background: There are limited data regarding treatment for failed balloon-expandable transcatheter heart valves (THVs) in redo-transcatheter aortic valve implantation (TAVI).

Aims: We aimed to assess THV performance, neoskirt height and expansion when performing redo-TAVI with the ACURATE platform inside a SAPIEN 3 (S3) compared to redo-TAVI with an S3 in an S3.

Methods: Redo-TAVI was performed on the bench using each available size of the S3, the ACURATE neo2 (ACn2) and the next-generation ACURATE Prime XL (AC XL) implanted at 2 different depths within 20 mm/23 mm/26 mm/29 mm S3s serving as the "failed" index THV.

Longitudinal trends in causes of death among adults with HIV on antiretroviral therapy in Europe and North America from 1996 to 2020: a collaboration of cohort studies.

Background: Mortality rates among people with HIV have fallen since 1996 following the widespread availability of effective antiretroviral therapy (ART). Patterns of cause-specific mortality are evolving as the population with HIV ages. We aimed to investigate longitudinal trends in cause-specific mortality among people with HIV starting ART in Europe and North America.

Impact of patient ancestry on heterogeneity of Sjögren's disease.

Objectives: We aimed to compare disease characteristics between primary Sjögren's syndrome (pSS) patients of African ancestry (AA) and Caucasian ancestry.

Methods: We conducted a retrospective, case-control study in a French national and European referral centre for pSS. All patients with pSS of AA were matched with two Caucasians patients having similar follow-up duration.

NT-proBNP and stem cell factor plasma concentrations are independently associated with cardiovascular outcomes in end-stage renal disease hemodialysis patients.

Aims: End-stage renal disease (ESRD) treated by chronic hemodialysis (HD) is associated with poor cardiovascular (CV) outcomes, with no available evidence-based therapeutics. A multiplexed proteomic approach may identify new pathophysiological pathways associated with CV outcomes, potentially actionable for precision medicine.

Methods And Results: The AURORA trial was an international, multicentre, randomized, double-blind trial involving 2776 patients undergoing maintenance HD.

New MraY Inhibitors with an Aminoribosyl Uridine Structure and an Oxadiazole.

New inhibitors of the bacterial transferase MraY from (MraY), based on the aminoribosyl uridine central core of known natural MraY inhibitors, have been designed to generate interaction of their oxadiazole linker with the key amino acids (H324 or H325) of the enzyme active site, as observed for the highly potent inhibitors carbacaprazamycin, muraymycin D2 and tunicamycin. A panel of ten compounds was synthetized notably thanks to a robust microwave-activated one-step sequence for the synthesis of the oxadiazole ring that involved the -acylation of an amidoxime and subsequent cyclization. The synthetized compounds, with various hydrophobic substituents on the oxadiazole ring, were tested against the MraY transferase activity.

Abbreviated Antiplatelet Therapy After Coronary Stenting in Patients With Myocardial Infarction at High Bleeding Risk.

Background: The optimal duration of antiplatelet therapy (APT) after coronary stenting in patients at high bleeding risk (HBR) presenting with an acute coronary syndrome remains unclear.

Objectives: The objective of this study was to investigate the safety and efficacy of an abbreviated APT regimen after coronary stenting in an HBR population presenting with acute or recent myocardial infarction.

Methods: In the MASTER DAPT trial, 4,579 patients at HBR were randomized after 1 month of dual APT (DAPT) to abbreviated (DAPT stopped and 11 months single APT or 5 months in patients with oral anticoagulants) or nonabbreviated APT (DAPT for minimum 3 months) strategies.

A phase 1b study of crenigacestat (LY3039478) in combination with gemcitabine and cisplatin or gemcitabine and carboplatin in patients with advanced or metastatic solid tumors.

Background: Notch signaling plays an integral role in development and tissue homeostasis. Inhibition of Notch signaling has been identified as a reasonable target for oncotherapy. Crenigacestat (LY3039478) is a potent Notch inhibitor that decreases Notch signaling and its downstream biologic effects.

Gain-of-function mutations in cause an NF-κB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome.

Objectives: To test the hypothesis that ROSAH (retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis and headache) syndrome, caused by dominant mutation in , is an autoinflammatory disease.

Methods: This cohort study systematically evaluated 27 patients with ROSAH syndrome for inflammatory features and investigated the effect of mutations on immune signalling. Clinical, immunologic and radiographical examinations were performed, and 10 patients were empirically initiated on anticytokine therapy and monitored.

COVID-19 infection among patients with autoinflammatory diseases: a study on 117 French patients compared with 1545 from the French RMD COVID-19 cohort: COVIMAI - the French cohort study of SARS-CoV-2 infection in patient with systemic autoinflammatory diseases.

Objective: There is little known about SARS-CoV-2 infection in patients with systemic autoinflammatory disease (SAID). This study aimed to describe epidemiological features associated with severe disease form and death. Mortality between patients with and without SAID hospitalised for SARS-CoV-2 infection was compared.

MRI and Molecular Characterization of Pediatric High-Grade Midline Thalamic Gliomas: The HERBY Phase II Trial.

Background Diffuse midline gliomas (DMG) are characterized by a high incidence of mutations and poorer outcome. The HERBY trial has provided one of the largest cohorts of pediatric DMGs with available radiologic, histologic-genotypic, and survival data. Purpose To define MRI and molecular characteristics of DMG.

ANtiangiogenic Second-line Lung cancer Meta-Analysis on individual patient data in non-small cell lung cancer: ANSELMA.

Background: Now that immunotherapy plus chemotherapy (CT) is one standard option in first-line treatment of advanced non-small cell lung cancer (NSCLC), there exists a medical need to assess the efficacy of second-line treatments (2LT) with antiangiogenics (AA). We performed an individual patient data meta-analysis to validate the efficacy of these combinations as 2LT.

Methods: Randomised trials of AA plus standard 2LT compared to 2LT alone that ended accrual before 2015 were eligible.

Breaking antimicrobial resistance by disrupting extracytoplasmic protein folding.

Antimicrobial resistance in Gram-negative bacteria is one of the greatest threats to global health. New antibacterial strategies are urgently needed, and the development of antibiotic adjuvants that either neutralize resistance proteins or compromise the integrity of the cell envelope is of ever-growing interest. Most available adjuvants are only effective against specific resistance proteins.

Outcomes and regional differences in practice in a worldwide coronary stent registry.

Objective: The primary objective was to assess the performance of a new generation thin-strut sirolimus-eluting coronary stent with abluminal biodegradable polymer in an all comer population. The secondary objective was to detail differences in contemporary percutaneous coronary intervention (PCI) practice worldwide.

Methods: e-Ultimaster was an all-comer, prospective, global registry (NCT02188355) with independent event adjudication enrolling patients undergoing PCI with the study stent.

Synthesis and biological studies of "Polycerasoidol" and "trans-δ-Tocotrienolic acid" derivatives as PPARα and/or PPARγ agonists.

2-Prenylated benzopyrans represent a class of natural and synthetic compounds showing a wide range of significant activities. Polycerasoidol is a natural prenylated benzopyran isolated from the stem bark of Polyalthia cerasoides (Annonaceae) that exhibits dual PPARα/γ agonism and an anti-inflammatory effect by inhibiting mononuclear leukocyte adhesion to the dysfunctional endothelium. Herein, we report the synthesis of three new series of prenylated benzopyrans containing one (series 1), two (series 2, "polycerasoidol" analogs) and three (series 3, "trans-δ-tocotrienolic acid" analogs) isoprenoid units in the hydrocarbon side chain at the 2-position of the chroman-6-ol (6-hydroxy-dihydrobenzopyran) scaffold.

2021 update of the EULAR points to consider on the use of immunomodulatory therapies in COVID-19.

Objectives: To update the EULAR points to consider (PtCs) on the use of immunomodulatory therapies in COVID-19.

Methods: According to the EULAR standardised operating procedures, a systematic literature review up to 14 July 2021 was conducted and followed by a consensus meeting of an international multidisciplinary task force. The new statements were consolidated by formal voting.

Identification of Copper-Containing Oxidoreductases in the Secretomes of Three Species with a Focus on Copper Radical Oxidases for the Biocatalytic Production of Fatty Aldehydes.

Copper radical alcohol oxidases (CRO-AlcOx), which have been recently discovered among fungal phytopathogens, are attractive for the production of fragrant fatty aldehydes. With the initial objective to investigate the secretion of CRO-AlcOx by natural fungal strains, we undertook time course analyses of the secretomes of three Colletotrichum species (C. graminicola, C.