Philippe JEAN-PIERRE

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• Type de publi. : Article dans une revue
• Date de publi. : 28/05/2021
• Auteurs : Kevin ZarcaMaroua MimouniHelena PereiraGilles ChatellierValérie VilgrainIsabelle Durand-ZaleskiEric AssenatElisabeth Delhom-ChristolBoris GuiuAlina IloncaJulie LonjonGeorges-Philippe PageauxMohamed Abdel-RehimWassim Al-LahamMohamed BouattourLaurent CasteraArnaud DieudonnéRachida LebtahiMaxime RonotAnnie SibertHélène BarraudChristophe BazinJean-Pierre BronowickiValérie LaurentElodie MathiasCarine Chagneau-DerrodeRémy PerdrisotChristine SilvainJean-Pierre TasuPatrick Borentain RenégerolamiOlivier MundlerJean-Francois SeitzVincent VidalChristophe AubéAntoine BouvierOlivier CouturierFrédéric ObertiLaurent VervuerenIsabelle Brenot-RossiJean-Luc RaoulAnthony Sar-RanJulia ChalayeCharlotte CostentinEmmanuel IttiHicham KobeiterAlain LucianiRené AdamMaïté LewinDidier SamuelJulien EdelineEtienne GarinYan RollandIsabelle ArchambeaudThomas EugeneEric FrampasC. CassinottoMartine GuyotJean-Baptiste HiriartBruno LapuyadeJulien VergniolPhilippe BachellierJulien DetourBernard DuclosMichel GregetFrancois HabersetzerAlessio ImperialePhilippe MerleAgnès RodeJulie MorvanEric Nguyen-KhacThierry YzetGuillaume BaudinPatrick ChevallierAbakar MahamatThierry PicheMicheline RazzoukPatrick HillonRomaric LoffroyMichel ToubeauJulie VincentGabriele BarabinoNadia BouariouaMuriel CuilleronMarie EcochardNathalie PrévotVincent LeroyJulie RouxChristian SengelValérie BourcierNathalie Ganne- CarrieOlivier SerorSylvie CostoThông DaoJean-Pierre PelageJérôme DumortierFrancesco GiammarilePierre-Jean ValetteNadia GhazzarOlivier PellerinGilles ManceauPierre WeinmannAlexandra Heurgue- BerlotClaude MarcusDaniele SommacaleMaria-Angéla Castilla-LièvreSophie MaitreLysiane Marthey
• Organismes : Direction de la Recherche Clinique et de l'Innovation [AP-HP] Centre d'Investigation Clinique Henri Mondor Centre for Research in Epidemiology and Statistics | Centre de Recherche Épidémiologie et Statistiques Direction de la Recherche Clinique et de l'Innovation [AP-HP] CIC - HEGP CIC - HEGP Centre de recherche sur l'Inflammation Direction de la Recherche Clinique et de l'Innovation [AP-HP] Centre d'Investigation Clinique Henri Mondor Epidemiology and Clinical Statistics for Tumor, Respiratory, and Resuscitation | Epidémiologie Clinique, STatistique, pour la Recherche en Santé Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi] Département radiologie diagnostique et interventionnelle Saint Eloi [CHRU Montpellier] Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi] Equipe IFTIM [ImViA - EA7535]
• Publié dans Clinical Therapeutics le 30/10/2020

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Résumé : Purpose: The SARAH (Sorafenib Versus Radioembolization in Advanced Hepatocellular Carcinoma) trial (ClinicalTrials.gov Identifier NCT01482442) did not show a significant survival benefit for patients treated with transarterial radioembolization (TARE) compared with continuous oral sorafenib. The improved toxicity profile of patients treated with TARE in the trial, however, could result in a quality of life benefit in economic evaluations. Our objective was to perform a cost-utility analysis of TARE versus sorafenib for locally advanced and inoperable hepatocellular carcinoma. Methods: This study used patient-level data of the SARAH trial regarding resource use, progression-free and overall survival, and quality of life for the within-trial period for the patients who received at least 1 dose of sorafenib or 1 treatment with TARE according to their randomization arm. Data were extrapolated by using a partitioned survival model that incorporated costs and health outcomes, measured in life-years and quality-adjusted life-years (QALYs). Findings: The use of TARE resulted in an average loss of 0.036 life-year and a gain of 0.006 QALY compared with sorafenib. The aerage cost for the TARE arm was €17,179 (95% CI, 9,926-24,280) higher than the sorafenib arm, for an incremental cost-effectiveness ratio of €3,153,086/QALY. The probabilistic sensitivity analysis revealed a 50% risk that the TARE strategy was dominated. TARE was consistently dominated by sorafenib or had an incremental cost-effectiveness ratio more than €450,000/QALY in all sensitivity analyses. Implications: This economic evaluation of SARAH found that using radioembolization with yttrium-90 microspheres for the treatment of hepatocellular carcinoma was not a cost-effective option at the usually accepted willingness-to-pay thresholds.

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Fichiers liés : 1-s2.0-S0149291821002137-am-1.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 27/05/2021
• Auteurs : Louis BernardCedric ArvieuxBenoit BrunschweilerSophie TouchaisSeverine AnsartJean-Pierre BruEric OziolCyril BoeriGuillaume GrasJerome DruonPhilippe RossetEric SennevilleHoucine BentayebDamien BouhourGwénaël Le MoalJocelyn MichonHugues AumaitreEmmanuel ForestierJean-Michel LaffosseThierry BéguéCatherine ChirouzeFrederic-Antoine DauchyEdouard DevaudBenoit MarthaDenis BurgotDavid BoutoilleEric StindelAurelien DinhPascale BémerBruno GiraudeauBertrand IssartelAgnès Caille
• Organismes : Centre Hospitalier Régional Universitaire de Besançon Laboratoire Chrono-environnement (UMR 6249) Bordeaux population health methodS in Patients-centered outcomes and HEalth ResEarch methodS in Patients-centered outcomes and HEalth ResEarch
• Publié dans New England Journal of Medicine le 29/10/2020

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Résumé : BACKGROUND: The management of prosthetic joint infection usually consists of a combination of surgery and antimicrobial therapy. The appropriate duration of antimicrobial therapy for this indication remains unclear. METHODS: We performed an open-label, randomized, controlled, noninferiority trial to compare 6 weeks with 12 weeks of antibiotic therapy in patients with microbiologically confirmed prosthetic joint infection that had been managed with an appropriate surgical procedure. The primary outcome was persistent infection (defined as the persistence or recurrence of infection with the initial causative bacteria, with an antibiotic susceptibility pattern that was phenotypically indistinguishable from that at enrollment) within 2 years after the completion of antibiotic therapy. Noninferiority of 6 weeks of therapy to 12 weeks of therapy would be shown if the upper boundary of the 95% confidence interval for the absolute between-group difference (the value in the 6-week group minus the value in the 12-week group) in the percentage of patients with persistent infection within 2 years was not greater than 10 percentage points. RESULTS: A total of 410 patients from 28 French centers were randomly assigned to receive antibiotic therapy for 6 weeks (205 patients) or for 12 weeks (205 patients). Six patients who withdrew consent were not included in the analysis. In the main analysis, 20 patients who died during follow-up were excluded, and missing outcomes for 6 patients who were lost to follow-up were considered to be persistent infection. Persistent infection occurred in 35 of 193 patients (18.1%) in the 6-week group and in 18 of 191 patients (9.4%) in the 12-week group (risk difference, 8.7 percentage points; 95% confidence interval, 1.8 to 15.6); thus, noninferiority was not shown. Noninferiority was also not shown in the per-protocol and sensitivity analyses. We found no evidence of between-group differences in the percentage of patients with treatment failure due to a new infection, probable treatment failure, or serious adverse events. CONCLUSIONS: Among patients with microbiologically confirmed prosthetic joint infections that were managed with standard surgical procedures, antibiotic therapy for 6 weeks was not shown to be noninferior to antibiotic therapy for 12 weeks and resulted in a higher percentage of patients with unfavorable outcomes. (Funded by Programme Hospitalier de Recherche Clinique, French Ministry of Health; DATIPO ClinicalTrials.gov number, NCT01816009.).

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• Type de publi. : Communication dans un congrès
• Date de publi. : 27/05/2021
• Auteurs : Philippe Jean-PierreDavid Perrain
• Organismes : Centre d'Économie et de Management de l'Océan Indien Institut d'Administration des Entreprises - La Réunion Centre d'Économie et de Management de l'Océan Indien Institut d'Administration des Entreprises - La Réunion

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• Type de publi. :
• Date de publi. : 27/05/2021
• Auteurs : Sophie GarnierMagdalena HarakalovaStefan WeissMichal MokryRichard IsnardLaëtitia Duboscq-BidotMichel KomajdaFrançois CambienJean-François DeleuzeMarcus DörrFolkert W AsselbergsEric VillardDavid-Alexandre TrégouëtPhilippe Charron
• Organismes : Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases University Medical Center [Utrecht] Universität Greifswald = University of Greifswald German Center for Cardiovascular Research University Medical Center [Utrecht] Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases Génomique cardiovasculaire Centre National de Génotypage Laboratory of Excellence GENMED [Paris] Universität Greifswald = University of Greifswald ICIN - Netherlands Heart Institute University College London [UCL] University Medical Center [Utrecht] Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases Assistance publique - Hôpitaux de Paris (AP-HP) Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases

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• Type de publi. : Article dans une revue
• Date de publi. : 27/05/2021
• Auteurs : Lorène ZerahDominique Bonnet-ZamponiAya AjroucheJean-Philippe ColletYann de RyckeFlorence Tubach
• Organismes : CHU Pitié-Salpêtrière [AP-HP] Institut Pierre Louis d'Epidémiologie et de Santé Publique Institut Pierre Louis d'Epidémiologie et de Santé Publique CHU Pitié-Salpêtrière [AP-HP] Institut Pierre Louis d'Epidémiologie et de Santé Publique Institut de cardiologie [CHU Pitié-Salpêtrière] Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases Groupe Action Institut Pierre Louis d'Epidémiologie et de Santé Publique CHU Pitié-Salpêtrière [AP-HP] Institut Pierre Louis d'Epidémiologie et de Santé Publique
• Publié dans Journal of Clinical Medicine le 29/10/2020

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Résumé : With the increase in prevalence of cardiovascular diseases, multimorbidity, and medical progress, oral antithrombotic (AT) combinations are increasingly prescribed. The aims of this study were to estimate the incidence of oral AT combinations, their appropriateness (defined as indications compliant with guidelines), and the related risk of major bleeding (i.e., leading to hospitalization) or death, among new users. We conducted a 5-year historical cohort study, using the French national healthcare database, including all individuals ≥ 45 years old with a first delivery of oral ATs between 1 January 2013 and 31 December 2017. The cumulative incidence of oral AT combinations was estimated with the Fine and Gray method, taking into account the competitive risk of death. We compared the cumulative incidence of major bleeding according to the type of oral AT treatment initiated at study entry (monotherapy or oral AT combinations). During the study period, 22,220 individuals were included (mean (SD) age 68 (12) years). The cumulative incidence of oral AT combinations at 5 years was 27.8% (95% confidence interval (CI) 26.8–28.9). Overall, 64% of any oral AT combinations did not comply with guidelines. The cumulative incidence of major bleeding and death in the whole cohort at 5 years was 4.1% (95% CI 3.7–4.6) and 10.8% (95% CI 10.1–11.6), respectively. Risk of major bleeding increased among individuals with oral AT combinations versus oral AT monotherapy at study entry (subdistribution hazard ratio sHR: 2.16 (1.01–4.63)); with no difference in terms of death. The use of oral AT combinations among oral AT users is frequent, often inappropriately prescribed, and associated with an increased risk of major bleeding.

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Fichiers liés : jcm-10-02367-v2.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 26/05/2021
• Auteurs : Clémence MercierMathieu PiocheEliane AlbuissonThierry PonchonJean-Michel GonzalèsMarc BarthetIsabelle BoytchevGeoffroy VanbiervlietClement Fortier BeaulieuFrederic PratArthur BelleJulien BranchePhilippe GrandvalJean-Christophe ValatsFranz RudlerTimothée WallenhorstStephane KochAurélie ComteNicolas WillietNicolas MusquerEmmanuel CoronAline DerosièreJean-Philippe Le MouelMarion SchaeferCaroline ChabotIsabelle ScheersPierre DeprezJean-Baptiste Chevaux
• Organismes : Centre Hospitalier Régional Universitaire de Nancy Laboratoire des applications thérapeutiques des ultrasons / Application des ultrasons à la thérapie Hôpital Edouard Herriot [CHU - HCL] Centre Hospitalier Régional Universitaire de Nancy Hôpital Edouard Herriot [CHU - HCL] Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille] Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille] Service d'Hépato-gastro-entérologie [APHP Kremlin-Bicêtre] Centre Hospitalier Universitaire de Nice Centre Hospitalier Universitaire de Nice Hôpital Cochin [AP-HP] Service de Gastro-entérologie [CHU Cochin] Hôpital Cochin [AP-HP] Service de Gastro-entérologie [CHU Cochin] Hôpital Claude Huriez [Lille] Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille] Centre de Recherche en Cancérologie de Marseille Centre Hospitalier Régional Universitaire [Montpellier] Centre Hospitalier Régional Universitaire [Montpellier] Université de Montpellier Hôpital Sud [CHU Rennes] Centre Hospitalier Régional Universitaire de Besançon Service de chirurgie pédiatrique [CHU Besançon] Centre Hospitalier Régional Universitaire de Besançon Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Service d'Hépato Gastroenterologie [CHU Amiens-Picardie] Service d'Hépato Gastroenterologie [CHU Amiens-Picardie] Centre Hospitalier Régional Universitaire de Nancy Centre Hospitalier Régional Universitaire de Nancy Cliniques Universitaires Saint-Luc [Bruxelles] Cliniques Universitaires Saint-Luc [Bruxelles] Centre Hospitalier Régional Universitaire de Nancy
• Publié dans Endoscopy le 22/10/2020

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Résumé : Introduction The aims of this retrospective multicenter study were to assess the technical success and adverse events of endoscopic retrograde cholangiopancreatography (ERCP) procedures in children in French and Belgian centers. Methods All children aged 1 day to 17 years who underwent ERCP between January 2008 and March 2019 in 15 tertiary care hospitals were retrospectively included. Results 271 children underwent 470 ERCP procedures. Clinical long-term follow-up was available for 72 % of our patients (340/470 procedures). The median age at intervention was 10.9 years. ERCP was therapeutic in 90 % (423/470) and diagnostic in cases of neonatal cholestasis in 10 % of the patients. The most common biliary indication was choledocholithiasis; the most common pancreatic indication was chronic pancreatitis. Biliary cannulation was successful in 92 % of cases (270/294); pancreatic cannulation in 96 % of cases (169/176); and planned therapeutic procedures in 92 % of cases (388/423). The overall complication rate was 19 % (65/340). The most common complication was post-ERCP pancreatitis (PEP) in 12 % of cases (40/340) and sepsis in 5 % (18/340). On univariate analyses, pancreatic stent removal was protective against PEP (odds ratio [OR] 0.1, 95 % confidence interval [CI] 0.01 – 0.75; P = 0.03), and sepsis was associated with history of liver transplantation (OR 7.27, 95 %CI 1.7 – 31.05; P = 0.01). Five patients had post-ERCP hemorrhage and two had intestinal perforation. All complications were managed with supportive medical care. There was no procedure-related mortality. Conclusion Our cohort demonstrates that ERCP can be performed safely with high success rates in many pancreaticobiliary diseases of children. The rate of adverse events was similar to that in previous reports.

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• Type de publi. :
• Date de publi. : 26/05/2021
• Auteurs : Jean-Philippe ChimierJérôme LivetIsabelle PichonDenis GodignonSandrine BartholomeJérôme Defaix
• Organismes : Cités, Territoires, Environnement et Sociétés Institut national de recherches archéologiques préventives Institut national de recherches archéologiques préventives De la Préhistoire à l'Actuel : Culture, Environnement et Anthropologie

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Résumé : Les pierres d’attente des morts correspondent à des dalles de pierre posées ou non sur des supports, aux dimensions variables mais ne dépassant qu’exceptionnellement 2 x 1 m. Il s’agit de reposoirs utilisés pour le cercueil lors de la levée du corps. Les pierres d’attente localisées à proximité des églises accueillent le défunt pour la cérémonie des funérailles.

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• Type de publi. : Article dans une revue
• Date de publi. : 26/05/2021
• Auteurs : Lorenzo MugnaiDarius Modirrousta-GalianBilly EdwardsQuentin ChangeatJeroen BouwmanGiuseppe MorelloAhmed Al-RefaieRobin BaeyensMichelle Fabienne BiegerDoriann BlainAmélie GressierGloria GuilluyYassin JaziriFlavien KieferMario MorvanWilliam PlurielMathilde PovedaNour SkafNiall WhitefordSam WrightKai Hou YipTiziano ZingalesBenjamin CharnayPierre DrossartJérémy LeconteOlivia VenotIngo WaldmannJean-Philippe Beaulieu
• Organismes : Dipartimento di Fisica [Roma La Sapienza] INAF - Osservatorio Astronomico di Palermo Dipartimento di Fisica e Chimica [Palermo] Department of Physics and Astronomy [UCL London] Department of Physics and Astronomy [UCL London] Max-Planck-Institut für Astronomie INAF - Osservatorio Astronomico di Palermo Instituto de Astrofisica de Canarias Department of Physics and Astronomy [UCL London] Institute of Astronomy [Leuven] College of Engineering, Mathematics and Physical Sciences [Exeter] Laboratoire d'études spatiales et d'instrumentation en astrophysique = Laboratory of Space Studies and Instrumentation in Astrophysics Institut d'Astrophysique de Paris Laboratoire d'études spatiales et d'instrumentation en astrophysique = Laboratory of Space Studies and Instrumentation in Astrophysics PLANETO - LATMOS Dipartimento di Fisica [Torino] INAF - Osservatorio Astrofisico di Torino Laboratoire d'Astrophysique de Bordeaux [Pessac] Laboratoire d'études spatiales et d'instrumentation en astrophysique = Laboratory of Space Studies and Instrumentation in Astrophysics Department of Physics and Astronomy [UCL London] Laboratoire d'Astrophysique de Bordeaux [Pessac] Laboratoire Interuniversitaire des Systèmes Atmosphériques Maison de la Simulation Laboratoire d'études spatiales et d'instrumentation en astrophysique = Laboratory of Space Studies and Instrumentation in Astrophysics Subaru Telescope Department of Physics and Astronomy [UCL London] Institute for Astronomy [Edinburgh] Centre for Exoplanet Science Department of Physics and Astronomy [UCL London] Department of Physics and Astronomy [UCL London] Laboratoire d'Astrophysique de Bordeaux [Pessac] Laboratoire d'études spatiales et d'instrumentation en astrophysique = Laboratory of Space Studies and Instrumentation in Astrophysics Institut d'Astrophysique de Paris Laboratoire d'études spatiales et d'instrumentation en astrophysique = Laboratory of Space Studies and Instrumentation in Astrophysics Laboratoire d'Astrophysique de Bordeaux [Pessac] Laboratoire Interuniversitaire des Systèmes Atmosphériques University College London [UCL] Institut d'Astrophysique de Paris School of Physical Sciences [Hobart]
• Publié dans The Astronomical Journal le 22/10/2020

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Résumé : We present a study on the spatially scanned spectroscopic observations of the transit of GJ 1132 b, a warm (∼500 K) super-Earth (1.13 R⊕) that was obtained with the G141 grism (1.125–1.650 μm) of the Wide Field Camera 3 (WFC3) on board the Hubble Space Telescope. We used the publicly available Iraclis pipeline to extract the planetary transmission spectra from the five visits and produced a precise transmission spectrum. We analyzed the spectrum using the TauREx3 atmospheric retrieval code, with which we show that the measurements do not contain molecular signatures in the investigated wavelength range and are best fit with a flat-line model. Our results suggest that the planet does not have a clear primordial, hydrogen-dominated atmosphere. Instead, GJ 1132 b could have a cloudy hydrogen-dominated atmosphere, have a very enriched secondary atmosphere, be airless, or have a tenuous atmosphere that has not been detected. Due to the narrow wavelength coverage of WFC3, these scenarios cannot be distinguished yet, but the James Webb Space Telescope may be capable of detecting atmospheric features, although several observations may be required to provide useful constraints.

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Fichiers liés : 2104.01873.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 25/05/2021
• Auteurs : Antoine RoquillyJean Denis MoyerOlivier HuetSigismond LasockiBenjamin CohenClaire Dahyot-FizelierKévin ChalardPhilippe SeguinCaroline JeantrelleVéronique VermeerschThomas GaillardRaphael CinottiDominique Demeure Dit LattePierre Joachim MaheMickael Vourc’hFlorian Pierre MartinAlice ChopinCéline LerebourgLaurent FletAnne ChiffoleauFanny FeuilletKarim Asehnoune
• Organismes : Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Hôpital Beaujon [AP-HP] CHRU Brest - Département d'Anesthésie Réanimation Optimisation des régulations physiologiques Centre Hospitalier Universitaire d'Angers CHU Trousseau [Tours] Centre hospitalier universitaire de Poitiers = Poitiers University Hospital Pharmacologie des anti-infectieux [U 1070] Université de Poitiers – UFR Santé [Faculté de Médecine et de Pharmacie] CHU Montpellier = Montpellier University Hospital Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Hôpital Beaujon [AP-HP] CHRU Brest - Département d'Anesthésie Réanimation Centre Hospitalier Universitaire d'Angers Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Hospitalier Universitaire de Nantes = Nantes University Hospital methodS in Patients-centered outcomes and HEalth ResEarch Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
• Publié dans JAMA Cardiology le 25/10/2020

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Résumé : Importance: Fluid therapy is an important component of care for patients with traumatic brain injury, but whether it modulates clinical outcomes remains unclear.Objective: To determine whether continuous infusion of hypertonic saline solution improves neurological outcome at 6 months in patients with traumatic brain injury.Design, setting, and participants: Multicenter randomized clinical trial conducted in 9 intensive care units in France, including 370 patients with moderate to severe traumatic brain injury who were recruited from October 2017 to August 2019. Follow-up was completed in February 2020.Interventions: Adult patients with moderate to severe traumatic brain injury were randomly assigned to receive continuous infusion of 20% hypertonic saline solution plus standard care (n = 185) or standard care alone (controls; n = 185). The 20% hypertonic saline solution was administered for 48 hours or longer if patients remained at risk of intracranial hypertension.Main outcomes and measures: The primary outcome was Extended Glasgow Outcome Scale (GOS-E) score (range, 1-8, with lower scores indicating worse functional outcome) at 6 months, obtained centrally by blinded assessors and analyzed with ordinal logistic regression adjusted for prespecified prognostic factors (with a common odds ratio [OR] >1.0 favoring intervention). There were 12 secondary outcomes measured at multiple time points, including development of intracranial hypertension and 6-month mortality.Results: Among 370 patients who were randomized (median age, 44 [interquartile range, 27-59] years; 77 [20.2%] women), 359 (97%) completed the trial. The adjusted common OR for the GOS-E score at 6 months was 1.02 (95% CI, 0.71-1.47; P = .92). Of the 12 secondary outcomes, 10 were not significantly different. Intracranial hypertension developed in 62 (33.7%) patients in the intervention group and 66 (36.3%) patients in the control group (absolute difference, -2.6% [95% CI, -12.3% to 7.2%]; OR, 0.80 [95% CI, 0.51-1.26]). There was no significant difference in 6-month mortality (29 [15.9%] in the intervention group vs 37 [20.8%] in the control group; absolute difference, -4.9% [95% CI, -12.8% to 3.1%]; hazard ratio, 0.79 [95% CI, 0.48-1.28]).Conclusions and relevance: Among patients with moderate to severe traumatic brain injury, treatment with continuous infusion of 20% hypertonic saline compared with standard care did not result in a significantly better neurological status at 6 months. However, confidence intervals for the findings were wide, and the study may have had limited power to detect a clinically important difference.

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• Type de publi. : Article dans une revue
• Date de publi. : 21/05/2021
• Auteurs : Sophie GarnierMagdalena HarakalovaStefan WeissMichal MokryVera Regitz-ZagrosekChristian HengstenbergThomas CappolaRichard IsnardEloisa ArbustiniStuart CookJessica van SettenJorg CalisHakon HakonarsonMichael MorleyKlaus StarkSanjay PrasadJin LiDeclan O'ReganMaurizia GrassoMartina Müller-NurasyidThomas MeitingerJean‐philippe EmpanaKonstantin StrauchMelanie WaldenbergerKenneth MarguilesChristine SeidmanGeorgios KararigasBenjamin MederJan HaasPierre BoutouyriePatrick LacolleyXavier JouvenJeanette ErdmannStefan BlankenbergThomas WichterVolker RuppertLuigi TavazziOlivier DubourgGérard RoizesRichard DorentPascal de GrooteLaurent FauchierJean-Noël TrochuJean-François AupetitZofia BilinskaMarine GermainUwe VölkerDaiane HemerichIbticem RajiDelphine Bacq-DaianCarole ProustPaloma RemiorManuel Gomez-BuenoKristin LehnertRenee MaasRobert OlasoGanapathi Varma SaripellaStephan FelixSteven McginnLaëtitia Duboscq-BidotAlain van MilCéline BesseVincent FontaineHélène BlanchéFlavie AderBrendan KeatingAngélique CurjolAnne BolandMichel KomajdaFrançois CambienJean‐françois DeleuzeMarcus DörrFolkert W AsselbergsEric VillardDavid-Alexandre TrégouëtPhilippe Charron
• Organismes : Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases University Medical Center [Utrecht] Universität Greifswald = University of Greifswald German Center for Cardiovascular Research University Medical Center [Utrecht] Charité - UniversitätsMedizin = Berlin University Medicine German Center for Cardiovascular Research University of Pennsylvania [Philadelphia] Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases Istituti di Ricovero e Cura a Carattere Scientifico National Heart Centre Singapore University Medical Center [Utrecht] University Medical Center [Utrecht] Children’s Hospital of Philadelphia University of Pennsylvania [Philadelphia] Universität Regensburg = University of Regensburg = Université de Ratisbonne [Allemagne] Royal Brompton Hospital [London, United Kingdom] Children’s Hospital of Philadelphia Imperial College London Istituti Clinici Scientifici Maugeri [Pavia] Helmholtz Zentrum München = German Research Center for Environmental Health Helmholtz Zentrum München = German Research Center for Environmental Health Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München Technische Universität Munchen = Technical University Munich = Université Technique de Munich Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases Helmholtz Zentrum München = German Research Center for Environmental Health Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München Universitätsmedizin der Johannes Gutenberg-Universität Mainz - University Medical Center of the Johannes Gutenberg-University Mainz [Germany] Helmholtz Zentrum München = German Research Center for Environmental Health German Center for Cardiovascular Research Perelman School of Medicine Harvard Medical School [Boston] University of Iceland [Reykjavik] Universität Heidelberg [Heidelberg] = Heidelberg University Stanford University Universität Heidelberg [Heidelberg] = Heidelberg University Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases Hôpital Européen Georges Pompidou [APHP] Défaillance Cardiovasculaire Aiguë et Chronique Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases Hôpital Européen Georges Pompidou [APHP] Universitätsmedizin der Johannes Gutenberg-Universität Mainz - University Medical Center of the Johannes Gutenberg-University Mainz [Germany] Universität zu Lübeck = University of Lübeck [Lübeck] Universitätklinikum Gießen und Marburg GmbH Universitätklinikum Gießen und Marburg GmbH Maria Cecilia Hospital Université de Versailles Saint-Quentin-en-Yvelines Institut de génétique humaine CHU Tenon [AP-HP] Hôpital cardiologique CHU Trousseau [Tours] ITX - unité de recherche de l'institut du thorax Centre hospitalier Saint Joseph - Saint Luc [Lyon] National Institute of Cardiology [Varsovie, Pologne] Bordeaux population health University of Medicine Greifswald German Center for Cardiovascular Research University Medical Center [Utrecht] Centre de Référence Maladies Cardiaques Héréditaires Centre National de Recherche en Génomique Humaine Laboratoire d'excellence en GENomique MEDicale Bordeaux population health Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain] Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain] Universität Greifswald = University of Greifswald German Center for Cardiovascular Research University Medical Center [Utrecht] Centre National de Recherche en Génomique Humaine Laboratoire d'excellence en GENomique MEDicale Swedish University of Agricultural Sciences = Sveriges lantbruksuniversitet Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases German Center for Cardiovascular Research Universität Greifswald = University of Greifswald Centre National de Recherche en Génomique Humaine Laboratoire d'excellence en GENomique MEDicale Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases University Medical Center [Utrecht] Centre National de Recherche en Génomique Humaine Laboratoire d'excellence en GENomique MEDicale Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases Centre d'Etude du Polymorphisme Humain Laboratoire d'excellence en GENomique MEDicale Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases CHU Pitié-Salpêtrière [AP-HP] Faculté de Pharmacie de Paris - Université Paris Descartes University of Pennsylvania [Philadelphia] Centre de Référence Maladies Cardiaques Héréditaires Centre National de Recherche en Génomique Humaine Laboratoire d'excellence en GENomique MEDicale Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases Groupe Hospitalier Paris Saint-Joseph Bordeaux population health Centre National de Recherche en Génomique Humaine Fondation Jean Dausset - Centre d’Etudes du Polymorphisme Humain [Paris] Laboratoire d'excellence en GENomique MEDicale German Center for Cardiovascular Research Universität Greifswald = University of Greifswald University Medical Center [Utrecht] University College London [UCL] Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases Bordeaux population health Laboratoire d'excellence en GENomique MEDicale Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases CHU Pitié-Salpêtrière [AP-HP] Centre de Référence Maladies Cardiaques Héréditaires
• Publié dans European Heart Journal le 30/10/2020

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Résumé : Abstract Aims Our objective was to better understand the genetic bases of dilated cardiomyopathy (DCM), a leading cause of systolic heart failure. Methods and results We conducted the largest genome-wide association study performed so far in DCM, with 2719 cases and 4440 controls in the discovery population. We identified and replicated two new DCM-associated loci on chromosome 3p25.1 [lead single-nucleotide polymorphism (SNP) rs62232870, P = 8.7 × 10−11 and 7.7 × 10−4 in the discovery and replication steps, respectively] and chromosome 22q11.23 (lead SNP rs7284877, P = 3.3 × 10−8 and 1.4 × 10−3 in the discovery and replication steps, respectively), while confirming two previously identified DCM loci on chromosomes 10 and 1, BAG3 and HSPB7. A genetic risk score constructed from the number of risk alleles at these four DCM loci revealed a 3-fold increased risk of DCM for individuals with 8 risk alleles compared to individuals with 5 risk alleles (median of the referral population). In silico annotation and functional 4C-sequencing analyses on iPSC-derived cardiomyocytes identify SLC6A6 as the most likely DCM gene at the 3p25.1 locus. This gene encodes a taurine transporter whose involvement in myocardial dysfunction and DCM is supported by numerous observations in humans and animals. At the 22q11.23 locus, in silico and data mining annotations, and to a lesser extent functional analysis, strongly suggest SMARCB1 as the candidate culprit gene. Conclusion This study provides a better understanding of the genetic architecture of DCM and sheds light on novel biological pathways underlying heart failure.

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