Liste des publications scientifiques du CHU de Clermont-Ferrand

Cette liste prend en compte l'ensemble des publications scientifiques du CHU référencées sur PubMed de 1973 au 31.12.2020

Auteurs : Carla, A; Pereira, B; Boukail, H; Jabaudon, M; , ; et al.

Revue : Respiratory research - ISSN : 1465-993X - NLMID : 101090633
Date de Publication : Avril 2020
Vol. : 21 Numéro 1 Pages : 81


Résumé : Subphenotypes were recently reported within clinical acute respiratory distress syndrome (ARDS), with distinct outcomes and therapeutic responses. Experimental models have long been used to mimic features of ARDS pathophysiology, but the presence of distinct subphenotypes among preclinical ARDS remains unknown. This review will investigate whether: 1) subphenotypes can be identified among preclinical ARDS models; 2) such subphenotypes can identify some responsive traits.We will include comparative preclinical (in vivo and ex vivo) ARDS studies published between 2009 and 2019 in which pre-specified therapies were assessed (interleukin (IL)-10, IL-2, stem cells, beta-agonists, corticosteroids, fibroblast growth factors, modulators of the receptor for advanced glycation end-products pathway, anticoagulants, and halogenated agents) and outcomes compared to a control condition. The primary outcome will be a composite of the four key features of preclinical ARDS as per the American Thoracic Society consensus conference (histologic evidence of lung injury, altered alveolar-capillary barrier, lung inflammatory response, and physiological dysfunction). Secondary outcomes will include the single components of the primary composite outcome, net alveolar fluid clearance, and death. MEDLINE, Embase, and Cochrane databases will be searched electronically and data from eligible studies will be extracted, pooled, and analyzed using random-effects models. Individual study reporting will be assessed according to the Animal Research: Reporting of In Vivo Experiments guidelines. Meta-regressions will be performed to identify subphenotypes prior to comparing outcomes across subphenotypes and treatment effects.This study will inform on the presence and underlying pathophysiological features of subphenotypes among preclinical models of ARDS and should help to determine whether sufficient evidence exists to perform preclinical trials of subphenotype-targeted therapies, prior to potential clinical translation.PROSPERO (ID: CRD42019157236).

Mesh : Adrenergic beta-Agonists/therapeutic use|Animals|Disease Models, Animal|Humans|Phenotype|Positive-Pressure Respiration/methods|Randomized Controlled Trials as Topic/methods|Respiratory Distress Syndrome/diagnosis/physiopathology/therapy|Treatment Outcome

Mots clés auteurs : /Acute respiratory distress syndrome/Preclinical/Subphenotypes/Systematic review protocol

Auteurs : Le Bacquer, O; Lanchais, K; Combe, K; Van Den Berghe, L; Walrand, S ;

Revue : Journal of cellular physiology - ISSN : 1097-4652 - NLMID : 0050222
Date de Publication : Septembre 2020


Résumé : Sarcopenia is an age-related loss of muscle mass associated with changes in skeletal muscle protein homeostasis due to lipid accumulation and anabolic resistance; changes that are also commonly described in obesity. Activation of the endocannabinoid system is associated with the development of obesity and insulin resistance, and with the perturbed skeletal muscle development. Taken together this suggests that endocannabinoids could be regulators of skeletal muscle protein homeostasis. Here we report that rimonabant, an antagonist for the CB1 receptor, can prevent dexamethasone-induced C2C12 myotube atrophy without affecting the mRNA expression of atrogin-1/MAFbx (a marker of proteolysis), which suggests it is involved in the control of protein synthesis. Rimonabant alone stimulates protein synthesis in a time- and dose-dependent manner through mTOR- and intracellular calcium-dependent mechanisms. CB1 agonists are unable to modulate protein synthesis or prevent the effect of rimonabant. Using C2C12 cells stably expressing an shRNA directed against CB1, or HEK293 cells overexpressing HA-tagged CB1, we demonstrated that the effect of rimonabant is unaffected by CB1 expression level. In summary, rimonabant can stimulate protein synthesis in C2C12 myotubes through a CB1-independent mechanism. These results highlight the need to identify non-CB1 receptor(s) mediating the pro-anabolic effect of rimonabant as potential targets for the treatment of sarcopenia, and to design new side-effect-free molecules that consolidate the effect of rimonabant on skeletal muscle protein synthesis.

Mots clés auteurs : /CB1 receptor/endocannabinoids/protein anabolism/sarcopenia/skeletal muscle

Auteurs : Luyt, CE; Forel, JM; Hajage, D; Papazian, L; , ; et al.

Revue : JAMA internal medicine - ISSN : 2168-6114 - NLMID : 101589534
Date de Publication : Février 2020
Vol. : 180 Numéro 2 Pages : 263-272


Résumé : The role of herpes simplex virus (HSV) reactivation on morbidity and mortality in patients in the intensive care unit requiring mechanical ventilation remains unknown.To determine whether preemptive treatment with intravenous acyclovir reduces the duration of mechanical ventilation in patients with HSV oropharyngeal reactivation.A double-blind, placebo-controlled randomized clinical trial was conducted in 16 intensive care units in France. Participants included 239 adults (age, >18 years) who received mechanical ventilation for at least 96 hours and continued to receive mechanical ventilation for 48 hours or more, with HSV oropharyngeal reactivation. Patients were enrolled between Févrierruary 2, 2014, and Févrierruary 22, 2018.Participants were randomized to receive intravenous acyclovir, 5 mg/kg, 3 times daily for 14 days or a matching placebo.The primary end point was ventilator-free days from randomization to day 60. Prespecified secondary outcomes included mortality at 60 days. Main analyses were conducted on an intention-to-treat basis.Of 239 patients enrolled and randomized, 1 patient withdrew consent, leaving 238 patients, with 119 patients in both the acyclovir and placebo (control) groups (median [IQR] age, 61 [50-70] years; 76 [32%] women) available for primary outcome measurement. On day 60, the median (IQR) numbers of ventilator-free days were 35 (0-53) for acyclovir recipients and 36 (0-50]) for controls (P?=?.17 for between-group comparison). Among secondary outcomes, 26 patients (22%) and 39 patients (33%) had died at day 60 (risk difference, 0.11, 95% CI, -0.004 to 0.22, P?=?.06). The adverse event frequency was similar for both groups (28% in the acyclovir group and 23% in the placebo group, P?=?.40), particularly acute renal failure post randomization affecting 3 acyclovir recipients (3%) and 2 controls (2%). Four patients (3%) in the acyclovir group vs none in the placebo group stopped the study drug for treatment-related adverse events.In patients receiving mechanical ventilation for 96 hours or more with HSV reactivation in the throat, use of acyclovir, 5 mg/kg, 3 times daily for 14 days, did not increase the number of ventilator-free days at day 60, compared with placebo. These findings do not appear to support routine preemptive use of acyclovir in this setting.ClinicalTrials.gov identifier: NCT02152358.

Mesh : Acyclovir/therapeutic use|Aged|Antiviral Agents/therapeutic use|Double-Blind Method|Female|France|Herpes Simplex/drug therapy|Humans|Male|Middle Aged|Oropharynx|Pharyngeal Diseases/drug therapy|Respiration, Artificial/statistics & numerical data|Respiratory Insufficiency/therapy|Treatment Outcome|Virus Activation

Auteurs : Sevrin, G; Massier, S; Chassaing, B; Billard, E; Barnich, N ; et al.

Revue : Gut microbes - ISSN : 1949-0984 - NLMID : 101495343
Date de Publication : Mai 2020
Vol. : 11 Numéro 3 Pages : 364-380


Résumé : The pathogenesis of Crohn's disease (CD) is multifactorial and involves genetic susceptibility, environmental triggers and intestinal microbiota. Adherent-invasive Escherichia coli (AIEC) are flagellated bacteria more prevalent in CD patients than in healthy subjects and promote chronic intestinal inflammation. We aim at deciphering the role of flagella and flagellin modulation by intestinal conditions. AIEC flagellum expression is required for optimal adhesion to and invasion of intestinal epithelial cells. Interestingly, differential flagellin regulation was observed between commensal E. coli (HS) and AIEC (LF82) strains: flagellum expression by AIEC bacteria, in contrast to that of commensal E. coli, is enhanced under intestinal conditions (the presence of bile acids and mucins). Flagella are involved in the ability of the AIEC LF82 strain to cross a mucus layer in vitro and in vivo, conferring a selective advantage in penetrating the mucus layer and reaching the epithelial surface. In a CEABAC10 mouse model, a non-motile mutant (LF82-?fliC) exhibits reduced colonization that is restored by a dextran sodium sulfate treatment that alters mucus layer integrity. Moreover, a mutant that continuously secretes flagellin (LF82-?flgM) triggers a stronger inflammatory response than the wild-type strain, and the mutant's ability to colonize the CEABAC10 mouse model is decreased. Overexpression of flagellin in bacteria in contact with epithelial cells can be detrimental to their virulence by inducing acute inflammation that enhances AIEC clearance. AIEC pathobionts must finely modulate flagellum expression during the infection process, taking advantage of their specific virulence gene regulation to improve their adaptability and flexibility within the gut environment.

Mesh : Animals|Bacterial Adhesion/genetics|Bacterial Proteins/genetics/metabolism|Caco-2 Cells|Colony Count, Microbial|Crohn Disease/microbiology|Escherichia coli/genetics/growth & development/pathogenicity/physiology|Escherichia coli Proteins/genetics/metabolism|Flagella/genetics/metabolism|Flagellin/genetics/metabolism|Gene Expression Regulation, Bacterial|HT29 Cells|Humans|Intestinal Mucosa/microbiology|Intestines/chemistry/microbiology|Mice|Mice, Inbred C57BL|Mucus/microbiology|Mutation|Phenotype

Auteurs : Blet, A; de Roquetaillade, C; Hartmann, O; Chousterman, BG; , ; et al.

Revue : Critical care (London, England) - ISSN : 1466-609X - NLMID : 9801902
Date de Publication : Février 2020
Vol. : 24 Numéro 1 Pages : 69
Mesh : Adrenomedullin|Humans|Intensive Care Units|Lactic Acid|Prognosis|Prospective Studies|Sepsis|Shock, Septic

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