Clinical significance of stratifying prostate cancer patients through specific circulating genes.

Patient stratification remains a challenge for optimal treatment of prostate cancer (PCa). This clinical heterogeneity implies intra-tumoural heterogeneity, with different prostate epithelial cell subtypes not all targeted by current treatments. We reported that such cell subtypes are traceable in liquid biopsies through representative transcripts.

Performance of a Region of Interest-based Algorithm in Diagnosing International Society of Urological Pathology Grade Group ≥2 Prostate Cancer on the MRI-FIRST Database-CAD-FIRST Study.

Background And Objective: Prostate multiparametric magnetic resonance imaging (MRI) shows high sensitivity for International Society of Urological Pathology grade group (GG) ≥2 cancers. Many artificial intelligence algorithms have shown promising results in diagnosing clinically significant prostate cancer on MRI. To assess a region-of-interest-based machine-learning algorithm aimed at characterising GG ≥2 prostate cancer on multiparametric MRI.

Fosfomycin-induced agranulocytosis: a case report and review of the literature.

Background: The intravenous form of fosfomycin, a bactericide antibiotic used to treat multiresistant bacterial infections is little prescribed. The most common reported adverse effects are hypokaliemia and hypernatremia. We describe a case of agranulocytosis, a rarely described side effect that may be fatal.

Integrating Echocardiography Parameters With Explainable Artificial Intelligence for Data-Driven Clustering of Primary Mitral Regurgitation Phenotypes.

Background: Primary mitral regurgitation (MR) is a heterogeneous clinical disease requiring integration of echocardiographic parameters using guideline-driven recommendations to identify severe disease.

Objectives: The purpose of this preliminary study was to explore novel data-driven approaches to delineate phenotypes of MR severity that benefit from surgery.

Methods: The authors used unsupervised and supervised machine learning and explainable artificial intelligence (AI) to integrate 24 echocardiographic parameters in 400 primary MR subjects from France (n = 243; development cohort) and Canada (n = 157; validation cohort) followed up during a median time of 3.

Quantification of primary mitral regurgitation by echocardiography: A practical appraisal.

The accurate quantification of primary mitral regurgitation (MR) and its consequences on cardiac remodeling is of paramount importance to determine the best timing for surgery in these patients. The recommended echocardiographic grading of primary MR severity relies on an integrated multiparametric approach. It is expected that the large number of echocardiographic parameters collected would offer the possibility to check the measured values regarding their congruence in order to conclude reliably on MR severity.

Clinical significance of myocardial contraction fraction in significant primary mitral regurgitation.

Background: The optimal timing for mitral valve (MV) surgery in asymptomatic patients with primary mitral regurgitation (MR) remains a matter of debate. Myocardial contraction fraction (MCF) - the ratio of the left ventricular (LV) stroke volume to that of the myocardial volume - is a volumetric measure of LV myocardial shortening independent of size or geometry.

Aim: To assess the relationship between MCF and outcome in patients with significant chronic primary MR due to prolapse managed in contemporary practice.

Post-discharge and long-term follow-up after an acute coronary syndrome: International Collaborative Group of CNCF position paper.

Introduction: Long-term follow-up after an acute coronary syndrome (ACS) presents a crucial challenge due to the high residual cardiovascular risk and the potential for major bleeding events. Although several treatment strategies are available, this article focuses on patients who have undergone percutaneous coronary intervention (PCI) for ACS, which is a frequent clinical situation. This position paper aims to support physicians in daily practice to improve the management of ACS patients.

Significance of Left Ventricular Ejection Time in Primary Mitral Regurgitation.

The optimal timing for mitral valve (MV) surgery in asymptomatic patients with primary mitral regurgitation (MR) remains controversial. We aimed at evaluating the relation between left ventricular ejection time (LVET) and outcome in patients with moderate or severe chronic primary MR because of prolapse. Clinical, Doppler echocardiographic, and outcome data prospectively collected from 302 patients (median age 61 [54 to 74] years, 34% women) with moderate or severe primary MR were analyzed.

Knockout in U251 Glioblastoma Cells Reduces Tumor Sphere Formation by Increasing Oxidative Stress and Suppressing Methionine Dependency.

Previously, the in vitro growth of cancer stem cells in the form of tumor spheres from five different brain cancer cell lines was found to be methionine-dependent. As this earlier work indicated that , a folate-dependent mitochondria aldehyde dehydrogenase gene, is upregulated in glioblastoma stem cells, we invalidated this gene using CRISPR-cas 9 technique in this present work. We reported here that this invalidation was effective in U251 glioblastoma cells, and no cas9 off target site could be detected by genome sequencing of the two independent knockout targeting either exon I or exon III.

Identifying early indicators of secondary peritonitis in critically ill patients with cirrhosis.

Ascitic fluid infection (AFI) is a life-threatening complication of cirrhosis. We aimed to identify early indicators of secondary peritonitis (SP), which requires emergency surgery, and to describe the outcomes of SP and spontaneous bacterial/fungal peritonitis (SBFP). Adults with cirrhosis and AFI admitted to 16 university or university-affiliated ICUs in France between 2002 and 2017 were studied retrospectively.

Hemodynamic Profiles of Cardiogenic Shock Depending on Their Etiology.

The pathophysiology of cardiogenic shock (CS) varies depending on its etiology, which may lead to different hemodynamic profiles (HP) and may help tailor therapy. We aimed to assess the HP of CS patients according to their etiologies of acute myocardial infarction (AMI) and acute decompensated chronic heart failure (ADCHF). We included patients admitted for CS secondary to ADCHF and AMI.

Characterization and Treatment of SARS-CoV-2 in Nasal and Bronchial Human Airway Epithelia.

In the current COVID-19 pandemic effective treatments represents a major challenge. However, the scarcity of biologically relevant pre-clinical models of SARS-CoV-2 infection imposes a significant barrier for scientific and medical progress, including the rapid transition of potentially effective treatments to the clinical setting. We use reconstituted human airway epithelia to isolate and then characterize the viral infection kinetics, tissue-level remodeling of the cellular ultrastructure, and transcriptional early immune signatures induced by SARS-CoV-2 in a physiologically relevant model.

Predictors of Outcomes Following Transcatheter Edge-to-Edge Mitral Valve Repair.

Transcatheter edge-to-edge mitral valve repair is a viable alternative to surgery in patients with severe mitral regurgitation and high surgical risk. Yet the specific group of patients who would optimally benefit from this therapy remains to be determined. Selection of patients for transcatheter strategy is currently based on surgical prognostic scores and technical feasibility.

[Intravascular large B cell lymphoma pathological findings led by positron emission tomography findings: About one case].

Intravascular large B cell lymphoma is a rare non-Hodgkin large B cell lymphoma disease, with heterogeneous clinical manifestation and difficult pathological diagnosis. Positron emission tomography may be helpfull in this context and has already been reported. A 45-year-old woman was admitted for persistent high fever, inflammatory syndrome and unexplained haemophagocytic syndrome.

Organ Transplantation in Hereditary Fibrinogen A α-Chain Amyloidosis: A Case Series of French Patients.

Rationale & Objective: Fibrinogen A α-chain amyloidosis (AFib amyloidosis) is a form of amyloidosis resulting from mutations in the fibrinogen A α-chain gene (FGA), causing progressive kidney disease leading to kidney failure. Treatment may include kidney transplantation (KT) or liver-kidney transplantation (LKT), but it is not clear what factors should guide this decision. The aim of this study was to characterize the natural history and long-term outcomes of this disease, with and without organ transplantation, among patients with AFib amyloidosis and various FGA variants.

Germline mutations in the new E1' cryptic exon of the gene in patients with tumours of von Hippel-Lindau disease spectrum or with paraganglioma.

Backgrounds: The incidence of germline mutations in the newly discovered cryptic exon (E1') of gene in patients with von Hippel-Lindau (VHL) disease and in patients with paraganglioma or pheochromocytoma (PPGL) is not currently known.

Methods: We studied a large international multicentre cohort of 1167 patients with a previous negative genetic testing. Germline DNA from 75 patients with a single tumour of the VHL spectrum ('Single VHL tumour' cohort), 70 patients with multiple tumours of the VHL spectrum ('Multiple VHL tumours' cohort), 76 patients with a VHL disease as described in the literature ('VHL-like' cohort) and 946 patients with a PPGL were screened for E1' genetic variants.

Etiology and Prognosis of Cardiogenic Shock in a Secondary Center without Surgical Back-Up.

Background: Cardiogenic shock (CS) remains a major challenge in contemporary cardiology. Data regarding CS etiologies and their prognosis are limited and mainly derived from tertiary referral centers.

Aims: To investigate the current etiologies of cardiogenic shock and their associated short- and long-term outcomes in a secondary center without surgical back-up.

How many patients are eligible for disease-modifying treatment in Alzheimer's disease? A French national observational study over 5 years.

Objective: We aimed to study the epidemiology of the prodromal and mild stages of Alzheimer's disease (AD) patients who are eligible for clinical trials with disease-modifying therapies.

Settings: We analysed two large complementary databases to study the incidence and characteristics of this population on a nationwide scope in France from 2014 to 2018. The National Alzheimer Database contains data from 357 memory centres and 90 private neurologists.

Successful transcatheter aortic valve implantation for severe aortic stenosis of a bicuspid valve with situs inversus totalis guided by advanced image processing: a case report.

Introduction: Transcatheter aortic valve implantation (TAVI) can be challenging in case of complex anatomy such as bicuspid aortic valve stenosis or situs inversus. This report illustrates a successful procedure in a patient with both conditions after careful pre-operative planning and per-operative guidance by means of a novel software.

Case Presentation: We report the case of a 71-year-old man that presented a type 0 bicuspid aortic valve stenosis and situs inversus.

Why should we extend transcatheter aortic valve implantation to low-risk patients? A comprehensive review.

Within the past decade, transcatheter aortic valve implantation (TAVI) has become established as the optimal treatment option for elderly, inoperable and high-risk patients with severe aortic stenosis, and is now recommended by international guidelines. Randomized controlled trials have demonstrated the non-inferiority of TAVI to open surgery in intermediate-risk patients and, most recently, in low-risk patients. Further randomized controlled trials are underway, but existing studies have already provided reassuring data in this cohort, and TAVI is offered routinely to younger and lower-risk patients in numerous centers.

Repurposing of Drugs as Novel Influenza Inhibitors From Clinical Gene Expression Infection Signatures.

Influenza virus infections remain a major and recurrent public health burden. The intrinsic ever-evolving nature of this virus, the suboptimal efficacy of current influenza inactivated vaccines, as well as the emergence of resistance against a limited antiviral arsenal, highlight the critical need for novel therapeutic approaches. In this context, the aim of this study was to develop and validate an innovative strategy for drug repurposing as host-targeted inhibitors of influenza viruses and the rapid evaluation of the most promising candidates in Phase II clinical trials.

Optimization of Next-Generation Sequencing Technologies for von Hippel Lindau (VHL) Mosaic Mutation Detection and Development of Confirmation Methods.

Von Hippel-Lindau disease (VHL) is a monogenic disorder characterized by the development of tumors affecting the central nervous system, kidney, pancreas, or adrenal glands, and due to germline mutations in the VHL tumor suppressor gene. About 5% of patients with a typical VHL phenotype have no mutation detected by conventional techniques, so a postzygotic VHL mosaicism can be suspected. The aim of this study was therefore to implement a next-generation sequencing (NGS) strategy for VHL mosaic mutation detection, including an optimization of the original Personal Genome Machine design by enrichment with oligonucleotides corresponding to amplicons with insufficient depth of coverage.