Yvan Devaux

Bio: Yvan Devaux is an academic researcher from Nancy-Université. The author has contributed to research in topics: Heart failure & Myocardial infarction. The author has an hindex of 38, co-authored 167 publications receiving 5735 citations. Previous affiliations of Yvan Devaux include French Institute of Health and Medical Research & University of Pittsburgh.

Circulating MicroRNA-208b and MicroRNA-499 Reflect Myocardial Damage in Cardiovascular Disease

Abstract: Background— Small RNA molecules, called microRNAs, freely circulate in human plasma and correlate with varying pathologies In this study, we explored their diagnostic potential in a selection of prevalent cardiovascular disorders Methods and Results— MicroRNAs were isolated from plasmas from well-characterized patients with varying degrees of cardiac damage: (1) acute myocardial infarction, (2) viral myocarditis, (3) diastolic dysfunction, and (4) acute heart failure Plasma levels of selected microRNAs, including heart-associated (miR-1, -133a, -208b, and -499), fibrosis-associated (miR-21 and miR-29b), and leukocyte-associated (miR-146, -155, and -223) candidates, were subsequently assessed using real-time polymerase chain reaction Strikingly, in plasma from acute myocardial infarction patients, cardiac myocyte–associated miR-208b and -499 were highly elevated, 1600-fold ( P <0005) and 100-fold ( P <00005), respectively, as compared with control subjects Receiver operating characteristic curve analysis revealed an area under the curve of 094 ( P <10−10) for miR-208b and 092 ( P <10−9) for miR-499 Both microRNAs correlated with plasma troponin T, indicating release of microRNAs from injured cardiomyocytes In viral myocarditis, we observed a milder but significant elevation of these microRNAs, 30-fold and 6-fold, respectively Plasma levels of leukocyte-expressed microRNAs were not significantly increased in acute myocardial infarction or viral myocarditis patients, despite elevated white blood cell counts In patients with acute heart failure, only miR-499 was significantly elevated (2-fold), whereas no significant changes in microRNAs studied could be observed in diastolic dysfunction Remarkably, plasma microRNA levels were not affected by a wide range of clinical confounders, including age, sex, body mass index, kidney function, systolic blood pressure, and white blood cell count Conclusions— Cardiac damage initiates the detectable release of cardiomyocyte-specific microRNAs-208b and -499 into the circulation

Long Noncoding RNAs in Patients With Acute Myocardial Infarction

Abstract: Rationale: Long noncoding RNAs (lncRNAs) constitute a novel class of noncoding RNAs that regulate gene expression. Although recent data suggest that lncRNAs may be associated with cardiac disease, little is known about lncRNAs in the setting of myocardial ischemia. Objective: To measure lncRNAs in patients with myocardial infarction (MI). Methods and Results: We enrolled 414 patients with acute MI treated by primary percutaneous coronary intervention. Blood samples were harvested at the time of reperfusion. Expression levels of 5 lncRNAs were measured in peripheral blood cells by quantitative polymerase chain reaction: hypoxia inducible factor 1A antisense RNA 2, cyclin-dependent kinase inhibitor 2B antisense RNA 1 (ANRIL), potassium voltage-gated channel, KQT-like subfamily, member 1 opposite strand/antisense transcript 1 (KCNQ1OT1), myocardial infarction–associated transcript, and metastasis-associated lung adenocarcinoma transcript 1. Levels of hypoxia inducible factor 1A antisense RNA 2, KCNQ1OT1, and metastasis-associated lung adenocarcinoma transcript 1 were higher in patients with MI than in healthy volunteers ( P <0.01), and levels of ANRIL were lower in patients with MI ( P =0.003). Patients with ST-segment–elevation MI had lower levels of ANRIL ( P <0.001), KCNQ1OT1 ( P <0.001), myocardial infarction–associated transcript ( P <0.001), and metastasis-associated lung adenocarcinoma transcript 1 ( P =0.005) when compared with patients with non–ST-segment–elevation MI. Levels of ANRIL were associated with age, diabetes mellitus, and hypertension. Patients presenting within 3 hours of chest pain onset had elevated levels of hypoxia inducible factor 1A antisense RNA 2 when compared with patients presenting later on. ANRIL, KCNQ1OT1, myocardial infarction–associated transcript, and metastasis-associated lung adenocarcinoma transcript 1 were significant univariable predictors of left ventricular dysfunction as assessed by an ejection fraction ≤40% at 4-month follow-up. In multivariable and reclassification analyses, ANRIL and KCNQ1OT1 improved the prediction of left ventricular dysfunction by a model, including demographic features, clinical parameters, and cardiac biomarkers. Conclusions: Levels of lncRNAs in blood cells are regulated after MI and may help in prediction of outcome. This motivates further investigation of the role of lncRNAs after MI. # Novelty and Significance {#article-title-43}

Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection.

Abstract: The potential for ischemic preconditioning to reduce infarct size was first recognized more than 30 years ago. Despite extension of the concept to ischemic postconditioning and remote ischemic conditioning and literally thousands of experimental studies in various species and models which identified a multitude of signaling steps, so far there is only a single and very recent study, which has unequivocally translated cardioprotection to improved clinical outcome as the primary endpoint in patients. Many potential reasons for this disappointing lack of clinical translation of cardioprotection have been proposed, including lack of rigor and reproducibility in preclinical studies, and poor design and conduct of clinical trials. There is, however, universal agreement that robust preclinical data are a mandatory prerequisite to initiate a meaningful clinical trial. In this context, it is disconcerting that the CAESAR consortium (Consortium for preclinicAl assESsment of cARdioprotective therapies) in a highly standardized multi-center approach of preclinical studies identified only ischemic preconditioning, but not nitrite or sildenafil, when given as adjunct to reperfusion, to reduce infarct size. However, ischemic preconditioning—due to its very nature—can only be used in elective interventions, and not in acute myocardial infarction. Therefore, better strategies to identify robust and reproducible strategies of cardioprotection, which can subsequently be tested in clinical trials must be developed. We refer to the recent guidelines for experimental models of myocardial ischemia and infarction, and aim to provide now practical guidelines to ensure rigor and reproducibility in preclinical and clinical studies on cardioprotection. In line with the above guideline, we define rigor as standardized state-of-the-art design, conduct and reporting of a study, which is then a prerequisite for reproducibility, i.e. replication of results by another laboratory when performing exactly the same experiment.

Long noncoding RNAs in cardiac development and ageing

Abstract: A large part of the mammalian genome is transcribed into noncoding RNAs. Long noncoding RNAs (lncRNAs) have emerged as critical epigenetic regulators of gene expression. Distinct molecular mechanisms allow lncRNAs either to activate or to repress gene expression, thereby participating in the regulation of cellular and tissue function. LncRNAs, therefore, have important roles in healthy and diseased hearts, and might be targets for therapeutic intervention. In this Review, we summarize the current knowledge of the roles of lncRNAs in cardiac development and ageing. After describing the definition and classification of lncRNAs, we present an overview of the mechanisms by which lncRNAs regulate gene expression. We discuss the multiple roles of lncRNAs in the heart, and focus on the regulation of embryonic stem cell differentiation, cardiac cell fate and development, and cardiac ageing. We emphasize the importance of chromatin remodelling in this regulation. Finally, we discuss the therapeutic and biomarker potential of lncRNAs.

Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia the official statement of the American Thoracic Society and the Infectious Disease Society of America (特集 救急診療ガイドライン) -- (海外のガイドライン)

Abstract: Executive Summary Introduction Methodology Used to Prepare the Guideline Epidemiology Incidence Etiology Major Epidemiologic Points Pathogenesis Major Points for Pathogenesis Modifiable Risk Factors Intubation and Mechanical Ventilation Aspiration, Body Position, and Enteral Feeding Modulation of Colonization: Oral Antiseptics and Antibiotics Stress Bleeding Prophylaxis, Transfusion, and Glucose Control Major Points and Recommendations for Modifiable Risk Factors Diagnostic Testing Major Points and Recommendations for Diagnosis Diagnostic Strategies and Approaches Clinical Strategy Bacteriologic Strategy Recommended Diagnostic Strategy Major Points and Recommendations for Comparing Diagnostic Strategies Antibiotic Treatment of Hospital-acquired Pneumonia General Approach Initial Empiric Antibiotic Therapy Appropriate Antibiotic Selection and Adequate Dosing Local Instillation and Aerosolized Antibiotics Combination versus Monotherapy Duration of Therapy Major Points and Recommendations for Optimal Antibiotic Therapy Specific Antibiotic Regimens Antibiotic Heterogeneity and Antibiotic Cycling Response to Therapy Modification of Empiric Antibiotic Regimens Defining the Normal Pattern of Resolution Reasons for Deterioration or Nonresolution Evaluation of the Nonresponding Patient Major Points and Recommendations for Assessing Response to Therapy Suggested Performance Indicators

A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response

Abstract: Recently, more than 1000 large intergenic noncoding RNAs (lincRNAs) have been reported. These RNAs are evolutionarily conserved in mammalian genomes and thus presumably function in diverse biological processes. Here, we report the identification of lincRNAs that are regulated by p53. One of these lincRNAs (lincRNA-p21) serves as a repressor in p53-dependent transcriptional responses. Inhibition of lincRNA-p21 affects the expression of hundreds of gene targets enriched for genes normally repressed by p53. The observed transcriptional repression by lincRNA-p21 is mediated through the physical association with hnRNP-K. This interaction is required for proper genomic localization of hnRNP-K at repressed genes and regulation of p53 mediates apoptosis. We propose a model whereby transcription factors activate lincRNAs that serve as key repressors by physically associating with repressive complexes and modulate their localization to sets of previously active genes.

Part 8: Post-cardiac arrest care: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care

Abstract: The recommendations in this 2015 American Heart Association (AHA) Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care are based on an extensive evidence review process that was begun by the International Liaison Committee on Resuscitation (ILCOR) after the publication of the 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations 1,2 and was completed in February 2015.3,4 In this in-depth evidence review process, ILCOR examined topics and then generated a prioritized list of questions for systematic review. Questions were first formulated in PICO (population, intervention, comparator, outcome) format,5 and then search strategies and inclusion and exclusion criteria were defined and a search for relevant articles was performed. The evidence was evaluated by the ILCOR task forces by using the standardized methodological approach proposed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group.6 The quality of the evidence was categorized based on the study methodologies and the 5 core GRADE domains of risk of bias, inconsistency, indirectness, imprecision, and other considerations (including publication bias). Then, where possible, consensus-based treatment recommendations were created. To create this 2015 Guidelines Update, the AHA formed 15 writing groups, with careful attention to manage conflicts of interest, to assess the ILCOR treatment recommendations and to write AHA treatment recommendations by using the AHA Class of Recommendation (COR) and Level of Evidence (LOE) system. The recommendations made in the Guidelines are informed by the ILCOR recommendations and GRADE classification, in the context of the delivery of medical care in North America. The AHA writing group made new recommendations only on topics specifically reviewed by ILCOR in 2015. This chapter delineates instances where the AHA writing group developed recommendations that are significantly stronger or weaker than the ILCOR statements. In the online …