Thomas BOUCHER

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• Type de publi. : Article dans une revue
• Date de publi. : 14/04/2020
• Auteurs : Cédric AnnweilerMélinda BeaudenonJennifer GautierRomain SimonVincent Dubée DubéeJustine GonsardElsa Parot-SchinkelAmal AidoudGuillaume AlbaretCédric AnnweilerAlexandra Audemard-VergerMarine AsfarJean BarréFlorian BerteauGaëlle BertolettiJean-Baptiste BeuscartAdrien BigotSophie BoucherElisabeth Botelho-NeversIsabelle Bourdel-MarchassonAnne Sophie BoureauAntoine BrangierCéline BrouessardMarie Laure BureauNoëlle CardinaudMichel CarlesKarine Castro-LionardThomas CelarierGuillaume ChapeletDavid ChirioEmilie ClabéPhilippe CodronJohan CourjonÉric CuaMarie Danet-LamasouAlexiane DecorbezMarine de la ChapelleElisa DemonchyEdouard DesvauxMonique D’hautefeuilleVincent DubéeGuillaume DuvalBertrand FougèrePaul GassieNicolas GiroultOlivier GuérinRégis HankardMarjorie HouvetStéphanie JobardCarole LacoutAurélie LafargueCécile Laubarie-MouretMaxime Le FlochSylvain Le GentilSébastien LléonartJocelyne LoisonRafaël MahieuFrançois MaillotLaure MartinezMarie MathieuAnthony MauclerePierre MénagerEmeline MichelThai Binh NguyenRomain OrdonezMarie OtekpoVirginie PichonFanny PoitauGary PommierValérie RabierKarine RissoHélène RivièreAgnès RouaudClaire Roubaud BaudronGuillaume SaccoFrédéric ScholastiqueEtienne Seronie-DoutriauxAchille TchallaWojciech TrzepizurYves-Marie Vandamme
• Organismes : Laboratoire de Psychologie des Pays de la Loire COVIT-TRIAL study group Centre Hospitalier Universitaire d'Angers COVIT-TRIAL study group Centre Hospitalier Universitaire d'Angers COVIT-TRIAL study group Centre Hospitalier Universitaire d'Angers COVIT-TRIAL study group CHU Saint-Antoine [AP-HP] Sorbonne Université COVIT-TRIAL study group Centre de Recherche en Cancérologie et Immunologie Nantes-Angers COVIT-TRIAL study group Centre Hospitalier Universitaire d'Angers COVIT-TRIAL study group Centre Hospitalier Régional Universitaire de Tours COVIT-TRIAL study group Pôle de Gérontologie Clinique Bordeaux Research In Translational Oncology [Bordeaux] COVIT-TRIAL study group Laboratoire de Psychologie des Pays de la Loire COVIT-TRIAL study group Service de médecine interne [CHU Caen] COVIT-TRIAL study group Centre Hospitalier Universitaire d'Angers COVIT-TRIAL study group COVIT-TRIAL study group CHU d'Angers Hôpital de la Cavale Blanche - CHRU Brest COVIT-TRIAL study group COVIT-TRIAL study group Evaluation des technologies de santé et des pratiques médicales - ULR 2694 COVIT-TRIAL study group Centre Hospitalier Régional Universitaire de Tours COVIT-TRIAL study group ED 515 - Complexité du vivant Centre Hospitalier Universitaire d'Angers Université d'Angers COVIT-TRIAL study group Groupe Immunité des Muqueuses et Agents Pathogènes COVIT-TRIAL study group Bordeaux population health COVIT-TRIAL study group COVIT-TRIAL study group Laboratoire de Psychologie des Pays de la Loire COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group CHU Limoges COVIT-TRIAL study group CHU Pointe-à-Pitre / Abymes [Guadeloupe] Université des Antilles Centre méditerranéen de médecine moléculaire COVIT-TRIAL study group COVIT-TRIAL study group Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] COVIT-TRIAL study group Université d'Angers COVIT-TRIAL study group Service d'infectiologie [CHU Nice] COVIT-TRIAL study group Université de Bordeaux COVIT-TRIAL study group MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale COVIT-TRIAL study group Centre méditerranéen de médecine moléculaire COVIT-TRIAL study group Service d'infectiologie [CHU Nice] COVIT-TRIAL study group Centre de résonance magnétique des systèmes biologiques COVIT-TRIAL study group Université Nice Sophia Antipolis - Faculté de Médecine COVIT-TRIAL study group COVIT-TRIAL study group Université Nice Sophia Antipolis - Faculté de Médecine COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group CHU Saint-Antoine [AP-HP] Sorbonne Université COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group COVIT-TRIAL study group
• Publié dans Trials le 31/10/2020

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Résumé : Abstract Background With the lack of effective therapy, chemoprevention, and vaccination against SARS-CoV-2, focusing on the immediate repurposing of existing drugs gives hope of curbing the COVID-19 pandemic. A recent unbiased genomics-guided tracing of the SARS-CoV-2 targets in human cells identified vitamin D among the three top-scoring molecules manifesting potential infection mitigation patterns. Growing pre-clinical and epidemiological observational data support this assumption. We hypothesized that vitamin D supplementation may improve the prognosis of COVID-19. The aim of this trial is to compare the effect of a single oral high dose of cholecalciferol versus a single oral standard dose on all-cause 14-day mortality rate in COVID-19 older adults at higher risk of worsening. Methods The COVIT-TRIAL study is an open-label, multicenter, randomized controlled superiority trial. Patients aged ≥ 65 years with COVID-19 (diagnosed within the preceding 3 days with RT-PCR and/or chest CT scan) and at least one worsening risk factor at the time of inclusion (i.e., age ≥ 75 years, or SpO2 ≤ 94% in room air, or PaO2/FiO2 ≤ 300 mmHg), having no contraindications to vitamin D supplementation, and having received no vitamin D supplementation > 800 IU/day during the preceding month are recruited. Participants are randomized either to high-dose cholecalciferol (two 200,000 IU drinking vials at once on the day of inclusion) or to standard-dose cholecalciferol (one 50,000 IU drinking vial on the day of inclusion). Two hundred sixty participants are recruited and followed up for 28 days. The primary outcome measure is all-cause mortality within 14 days of inclusion. Secondary outcomes are the score changes on the World Health Organization Ordinal Scale for Clinical Improvement (OSCI) scale for COVID-19, and the between-group comparison of safety. These outcomes are assessed at baseline, day 14, and day 28, together with the serum concentrations of 25(OH)D, creatinine, calcium, and albumin at baseline and day 7. Discussion COVIT-TRIAL is to our knowledge the first randomized controlled trial testing the effect of vitamin D supplementation on the prognosis of COVID-19 in high-risk older patients. High-dose vitamin D supplementation may be an effective, well-tolerated, and easily and immediately accessible treatment for COVID-19, the incidence of which increases dramatically and for which there are currently no scientifically validated treatments. Trial registration ClinicalTrials.gov NCT04344041 . Registered on 14 April 2020 Trial status Recruiting. Recruitment is expected to be completed in April 2021.

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Fichiers liés : 13063_2020_Article_4928.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 05/03/2020
• Auteurs : Eloïse GiabicaniMarjolaine WillemsVirginie SteunouSandra Chantot-BastaraudNathalie ThibaudWalid Abi HabibSalah AzziBich LamLaurence BérardHélène Bony-TrifunovicCécile BrachetElise Brischoux-BoucherEmmanuelle CaldaguesRegis CoutantMarie-Laure CuvelierGeorges GelwaneIsabelle GuemasMuriel HouangBertrand IsidorClaire JeandelJames LespinasseCatherine Naud-SaudreauMonique Jesuran-PerelroizenLaurence PerrinJuliette PiardClaire SechterPierre-François SouchonCaroline StoreyDomitille ThomasYves Le BoucSylvie RossignolIrène NetchineFrédéric Brioude
• Organismes : Institut National de la Santé et de la Recherche Médicale Sorbonne Université Institut des Neurosciences de Montpellier Service de génétique médicale [Montpellier]
• Publié dans Journal of Medical Genetics le 26/10/2020

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Résumé : Background The type 1 insulin-like growth factor receptor (IGF1R) is a keystone of fetal growth regulation by mediating the effects of IGF-I and IGF-II. Recently, a cohort of patients carrying an IGF1R defect was described, from which a clinical score was established for diagnosis. We assessed this score in a large cohort of patients with identified IGF1R defects, as no external validation was available. Furthermore, we aimed to develop a functional test to allow the classification of variants of unknown significance (VUS) in vitro. Methods DNA was tested for either deletions or single nucleotide variant (SNV) and the phosphorylation of downstream pathways studied after stimulation with IGF-I by western blot analysis of fibroblast of nine patients. Results We detected 21 IGF1R defects in 35 patients, including 8 deletions and 10 heterozygous, 1 homozygous and 1 compound-heterozygous SNVs. The main clinical characteristics of these patients were being born small for gestational age (90.9%), short stature (88.2%) and microcephaly (74.1%). Feeding difficulties and varying degrees of developmental delay were highly prevalent (54.5%). There were no differences in phenotypes between patients with deletions and SNVs of IGF1R . Functional studies showed that the SNVs tested were associated with decreased AKT phosphorylation. Conclusion We report eight new pathogenic variants of IGF1R and an original case with a homozygous SNV. We found the recently proposed clinical score to be accurate for the diagnosis of IGF1R defects with a sensitivity of 95.2%. We developed an efficient functional test to assess the pathogenicity of SNVs, which is useful, especially for VUS.

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• Type de publi. : Communication dans un congrès
• Date de publi. : 25/02/2020
• Auteurs : Etienne TerrenoireDidier A. HauglustaineThomas GasserOlivier Penanhoat
• Organismes : DMPE, ONERA, Université Paris Saclay (COmUE) [Palaiseau] Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] Modelling the Earth Response to Multiple Anthropogenic Interactions and Dynamics International Institute for Applied Systems Analysis [Laxenburg] Safran Aircraft Engines

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Résumé : Aviation emissions are estimated to contribute to 5 % (2–14 %, 90 % likelihood range) of the anthropogenic radiative forcing of climate with an uncertainty dominated by non-CO2 effects (Lee et al., 2010). Even if the level of scientific understanding is considered to be high by the IPCC for present-day aviation CO2 impact compared to other non-CO2 forcers (e.g. ozone, aerosols and contrails), the future (2050) aviation CO2 climate impact remains highly uncertain. One major reason of these varying estimates is linked to the inherent assumptions made in the development of future global emission scenarios such as the one from international aviation (Boucher et al., 2016). Hence, using the compact Earth System Model (ESM) OSCARv2.2 we quantify the climate impact of present and future (up to 2100) civil aviation carbon dioxide (CO2) emissions using eight aviation scenarios ranging from 386 Mt CO2/year (Factor 2 scenario) to 2338 Mt CO2/year (ICAO/CAEP scenario) in 2050. This approach will allow quantifying the uncertainty due to the difficulty to estimate the future mitigation effort. Another originality of the paper is that the influence of other emission sectors is evaluated using two background Representative Concentrations Pathways (RCP2.6 and RCP6.0). Results show that in 2050, on a climate trajectory in line with the Paris Agreement limiting the global warming below 2 °C (RCP2.6), the impact of the aviation CO2 emissions ranges from 26 ± 2 mK (1.4 % of the total global warming associated with all fossil fuel emissions) for an ambitious mitigation strategy scenario (Factor 2) to 39 ± 4 mK (2.0 % of the total global warming) for the least ambitious mitigation scenario of the study (ICAO-CAEP). On the longer term, if no significant emission mitigation is implemented for the aviation sector, the associated warming could further increase and reach a value of 100 mK in 2100 (ICAO/CAEP), which corresponds to 5.2 % of the total global temperature increase from total fossil fuel CO2 emissions under RCP2.6.

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Fichiers liés : DMPE20020.1591356752_preprint.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 15/02/2020
• Auteurs : Agnès MeybeckEnagnon-Kazali AlidjinouThomas HuleuxAnne BoucherMacha TetartPhilippe ChoisyLaurence BocketFaiza AjanaOlivier Robineau
• Organismes : Centre Hospitalier Gustave Dron [Tourcoing] Laboratoire de Virologie - ULR 3610 Centre Hospitalier Gustave Dron [Tourcoing] Centre Hospitalier de Tourcoing Centre Hospitalier de Tourcoing Centre Hospitalier de Tourcoing Laboratoire de Virologie - ULR 3610 Centre Hospitalier Gustave Dron [Tourcoing] Evaluation des technologies de santé et des pratiques médicales - ULR 2694
• Publié dans AIDS Patient Care and STDs le 26/10/2020

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Résumé : Issues have been raised concerning clinical relevance of HIV-1 proviral DNA genotypic resistance test (DNA GRT). To assess impact of DNA GRT on choice of antiretroviral therapy (ART) and subsequent virological outcome, we retrospectively reviewed decision-making and viral load (VL) evolution following DNA GRT performed in our center between January 2012 and December 2017, except those prescribed within the framework of a clinical trial. A total of 304 DNA GRTs were included, 185 (62%) performed in a context of virological success. Only 34% of tests were followed by ART change, more frequently in situation of virological success (39% vs. 26%, p = 0.02). In this situation, ART change guided by DNA GRT led to VL >20 copies/mL after 6 months in 5% of cases. In multivariate analysis, higher HIV DNA quantification (p = 0.01) was associated with occurrence of viremia. A higher nadir of CD4 count (p = 0.04) and a longer time with VL <20 copies/mL (p = 0.04) were independently associated with a lower risk of viremia. In situation of low-level viremia, ART change guided by DNA GRT led to VL <20 copies/mL after 6 months in 52% of cases, while decision to maintain the same treatment led to VL <20 copies/mL in 74% of cases. In multivariate analysis, longer time with VL >20 copies/mL (p = 0.02) was associated with persistence of virological replication. In conclusion, in situation of virological success, use of DNA GRT in addition to analysis of historical RNA GRT to guide ART optimization appears safe. Its prescription framework in situation of low-level viremia deserves to be better defined.

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• Type de publi. : Article dans une revue
• Date de publi. : 15/01/2020
• Auteurs : Pierre-Régis BurgelAnne MunckIsabelle DurieuRaphaël ChironLaurent MelyAnne PrevotatMarlene Murris-EspinMichele PorzioMichel AbelyPhilippe ReixChristophe MarguetJulie MaceyIsabelle Sermet-GaudelusHarriet CorvolStéphanie BuiL. LemonnierClémence DehillotteJennifer da SilvaJean-Louis PaillasseurDominique HubertJulie MounardClaire PouletCinthia RamesChristine PersonFrançoise TroussierThierry UrbanMarie-Laure DalphinJean-Claude DalphinDidier PernetBénédicte Richaud-ThiriezMichaël FayonKarine CampbellMuriel LauransCorinne BorderonMarie-Christine HeraudAndré LabbéSylvie MontcouquiolLaurence BassinetNatascha RemusAnnlyse FantonAnne Houzel-CharavelFrédéric HuetStéphanie Perez-MartinAmale Boldron-GhaddarManuela ScalbertBoubou CamaraCatherine LlerenaIsabelle PinSébastien QuétantAurélie CottereauAntoine DeschildreAlice GicquelloThierry PérezLidwine Stervinou-WemeauCaroline ThumerelleBenoit WallaertNathalie WizlaJane LanguepinCéline MénétreyMagalie Dupuy-GrassetLucie BazusClélia BuchsVirginie JubinMarie-Christine Werck-GalloisCatherine MainguyThomas PerrinAgnès Toutain-RigoletStéphane DuruptQuitterie ReynaudRaphaele Nove-JosserandMelisande Baravalle-EinaudiBérangère ColteyNadine DufeuJean-Christophe DubusNathalie StremlerD. CaimmiYves BillonJocelyne DerelleSébastien KiefferAnne-Sophie PichonCyril SchweitzerAurélie TatopoulosSarah AbbesTiphaine BihouéeIsabelle Danner-BoucherValérie DavidAlain HalounAdrien TissotSylvie LeroyCarole Bailly-PicciniAnnick ClémentAline TamaletIsabelle HonoréReem KanaanClémence MartinCécile BaillyFrédérique ChédevergneJacques de BlicBrigitte FaurouxMurielle Le BourgeoisBertrand DelaisiMichèle GérardinBruno RavoninjatovoChantal BelleguicBenoît DesruesGraziella BrinchaultMichel DagorneEric DeneuvilleSylvaine LefeuvreAnne DirouJean Le BihanSophie RamelStéphane DominiqueAnnabelle PayetRomain KesslerVincent RosnerLaurence WeissSandra de MirandaDominique GrenetAbdoul HamidClément PicardFrançois BrémontAlain DidierGéraldine LabouretMarie MittaineLaurent TêtuLaure CossonCharlotte GirautAnne-Cécile HenrietJulie MankikianSophie MarchandSandrine HugéVéronique StorniEmmanuelle Coirier-Duet
• Organismes : Hôpital Cochin [AP-HP] Institut Cochin Hôpital Robert Debré Hospices Civils de Lyon Health Service and Performance Research Université de Montpellier Centres de Ressources et de Compétences de la Mucoviscidose [Montpellier] Hôpital Renée Sabran [CHU - HCL] Service de Pneumologie et Immuno-Allergologie [CHU LIlle] Université de Lille Centre de Ressources et de Compétences en Mucoviscidose [CHU Toulouse] Fédération de Médecine Translationnelle de Strasbourg Hôpitaux Universitaires de Strasbourg Hôpital universitaire Robert Debré [Reims] Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 Hospices Civils de Lyon Groupe de Recherche sur l'Adaptation Microbienne Service de pneumologie, allergologie, mucoviscidose pédiatrique [Rouen] Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] Hôpital Necker - Enfants Malades [AP-HP] Institut Necker Enfants-Malades Mucoviscidose: physiopathologie et phénogénomique [CRSA] CHU Trousseau [APHP] Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] CIC Bordeaux Association Vaincre la mucoviscidose Association Vaincre la mucoviscidose Institut Cochin CIC - Mère Enfant Necker Cochin Paris Centre EFFI-STAT Hôpital Cochin [AP-HP] CHU Amiens-Picardie CHU Amiens-Picardie CHU Amiens-Picardie Centre Hospitalier Universitaire d'Angers Centre Hospitalier Universitaire d'Angers Centre Hospitalier Universitaire d'Angers Centre Hospitalier Régional Universitaire de Besançon Centre Hospitalier Régional Universitaire de Besançon Centre Hospitalier Régional Universitaire de Besançon Centre Hospitalier Régional Universitaire de Besançon CHU de Bordeaux Pellegrin [Bordeaux] CHU Caen Normandie – Centre Hospitalier Universitaire de Caen Normandie CHU Caen Normandie – Centre Hospitalier Universitaire de Caen Normandie CHU Clermont-Ferrand CHU Clermont-Ferrand CHU Clermont-Ferrand CHU Clermont-Ferrand Centre Hospitalier Intercommunal de Créteil Centre Hospitalier Intercommunal de Créteil CHU Dijon CHU Dijon CHU Dijon CHU Dijon Hôpital Alexandra Lepève – Centre Hospitalier de Dunkerque Hôpital Alexandra Lepève – Centre Hospitalier de Dunkerque Centre Hospitalier Universitaire [CHU Grenoble] Centre Hospitalier Universitaire [CHU Grenoble] Centre Hospitalier Universitaire [CHU Grenoble] Centre Hospitalier Universitaire [CHU Grenoble] Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 Centre Hospitalier Régional Universitaire [CHU Lille] Hôpital Jeanne de Flandres Service de Pneumologie et Immuno-Allergologie [CHU LIlle] Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 Centre Hospitalier Régional Universitaire [CHU Lille] Centre Hospitalier Régional Universitaire [CHU Lille] Centre Hospitalier Régional Universitaire [CHU Lille] Centre Hospitalier Régional Universitaire [CHU Lille] CHU Limoges CHU Limoges CHU Limoges Hospices Civils de Lyon Hospices Civils de Lyon Hospices Civils de Lyon Hospices Civils de Lyon Hospices Civils de Lyon Hospices Civils de Lyon Hospices Civils de Lyon Hospices Civils de Lyon Hospices Civils de Lyon Hospices Civils de Lyon Assistance Publique - Hôpitaux de Marseille Assistance Publique - Hôpitaux de Marseille Assistance Publique - Hôpitaux de Marseille Assistance Publique - Hôpitaux de Marseille Assistance Publique - Hôpitaux de Marseille Centre Hospitalier Régional Universitaire [Montpellier] Centre Hospitalier Régional Universitaire de Nancy Centre Hospitalier Régional Universitaire de Nancy Centre Hospitalier Régional Universitaire de Nancy Centre Hospitalier Régional Universitaire de Nancy Centre Hospitalier Régional Universitaire de Nancy Centre Hospitalier Régional Universitaire de Nancy 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 Nice Centre Hospitalier Universitaire de Nice CHU Trousseau [APHP] CHU Trousseau [APHP] Hôpital Cochin [AP-HP] Hôpital Cochin [AP-HP] Hôpital Cochin [AP-HP] Hôpital Necker - Enfants Malades [AP-HP] Hôpital Necker - Enfants Malades [AP-HP] Hôpital Necker - Enfants Malades [AP-HP] Hôpital Necker - Enfants Malades [AP-HP] Hôpital Necker - Enfants Malades [AP-HP] Hôpital Robert Debré Hôpital Robert Debré Hôpital universitaire Robert Debré [Reims] Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Hôpital de Saint-Brieuc [Hôpital Yves Le Foll] Hôpital de Saint-Brieuc [Hôpital Yves Le Foll] Hôpital de Saint-Brieuc [Hôpital Yves Le Foll] Fondation ILDYS Fondation ILDYS Fondation ILDYS CHU Rouen Centre Hospitalier Universitaire de La Réunion Hôpitaux Universitaires de Strasbourg Hôpitaux Universitaires de Strasbourg Hôpitaux Universitaires de Strasbourg Hôpital Foch [Suresnes] Hôpital Foch [Suresnes] Hôpital Foch [Suresnes] Hôpital Foch [Suresnes] Centre Hospitalier Universitaire de Toulouse Centre Hospitalier Universitaire de Toulouse Centre Hospitalier Universitaire de Toulouse Centre Hospitalier Universitaire de Toulouse Centre Hospitalier Universitaire de Toulouse Centre Hospitalier Régional Universitaire de Tours Centre Hospitalier Régional Universitaire de Tours Centre Hospitalier Régional Universitaire de Tours Centre Hospitalier Régional Universitaire de Tours Centre Hospitalier Régional Universitaire de Tours Centre hospitalier Bretagne Atlantique (Morbihan) Centre hospitalier Bretagne Atlantique (Morbihan) Centre Hospitalier de Versailles André Mignot
• Publié dans American Journal of Respiratory and Critical Care Medicine le 26/10/2020

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Résumé : Rationale: Lumacaftor-ivacaftor is a CFTR (cystic fibrosis transmembrane conductance regulator) modulator combination recently approved for patients with cystic fibrosis (CF) homozygous for the Phe508del mutation.Objectives: To evaluate the safety and effectiveness of lumacaftor-ivacaftor in adolescents (≥12 yr) and adults (≥18 yr) in a real-life postapproval setting. Methods: The study was conducted in the 47 CF reference centers in France. All patients who initiated lumacaftor-ivacaftor from January 1 to December 31, 2016, were eligible. Patients were evaluated for lumacaftor-ivacaftor safety and effectiveness over the first year of treatment following the French CF Learning Society's recommendations. Measurements and Main Results: Among the 845 patients (292 adolescents and 553 adults) who initiated lumacaftor-ivacaftor, 18.2% (154 patients) discontinued treatment, often owing to respiratory (48.1%, 74 patients) or nonrespiratory (27.9%, 43 patients) adverse events. In multivariable logistic regression, factors associated with increased rates of discontinuation included adult age group, percent predicted FEV1 (ppFEV1) less than 40%, and numbers of intravenous antibiotic courses during the year before lumacaftor-ivacaftor initiation. Patients with continuous exposure to lumacaftor-ivacaftor showed an absolute increase in ppFEV1 (+3.67%), an increase in body mass index (+0.73 kg/m2), and a decrease in intravenous antibiotic courses by 35%. Patients who discontinued treatment had significant decrease in ppFEV1, without improvement in body mass index or decrease in intravenous antibiotic courses. Conclusions: Lumacaftor-ivacaftor was associated with improvement in lung disease and nutritional status in patients who tolerated treatment. Adults who discontinued lumacaftor-ivacaftor, often owing to adverse events, were found at high risk of clinical deterioration.

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• Type de publi. : Article dans une revue
• Date de publi. : 01/01/2020
• Auteurs : Vincent Dubée DubéePierre-Marie RoyBruno VielleElsa Parot-SchinkelOdile BlanchetAstrid DarsonvalCaroline LefeuvreChadi AbbaraSophie BoucherEdouard DevaudOlivier RobineauPatrick RispalThomas GuimardEmma d'AnglejeanSylvain DiamantisMarc-Antoine CustaudIsabelle PellierAlain Mercat
• Organismes : ATOMycA Centre Hospitalier Universitaire d'Angers MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale Centre Hospitalier Universitaire d'Angers Centre Hospitalier Universitaire d'Angers Centre de Ressources Biologiques [CHU d'Angers] Centre Hospitalier Universitaire d'Angers Département de Pharmacie [CHU d'Angers] Centre Hospitalier Universitaire d'Angers Laboratoire de virologie [CHU Angers] Centre Hospitalier Universitaire d'Angers Département de Pharmacologie-Toxicologie [CHU Angers] MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale Centre Hospitalier Universitaire d'Angers Centre Hospitalier René Dubos [Pontoise] Centre Hospitalier Tourcoing Service de Médecine Interne [Agen] Centre Hospitalier Départemental Vendée Centre Hospitalier de Versailles André Mignot Groupe Hospitalier Sud Ile-de-France MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale Centre Hospitalier Universitaire d'Angers ATOMycA Université d'Angers Centre Hospitalier Universitaire d'Angers
• Publié dans Clinical Microbiology and Infection le 30/10/2020

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Résumé : Objectives: To determine whether hydroxychloroquine decreases the risk of adverse outcome in patients with mild to moderate coronavirus disease 2019 (COVID-19) at high risk of worsening. Methods: We conducted a multicentre randomized double-blind placebo-controlled trial evaluating hydroxychloroquine in COVID-19 patients with at least one of the following risk factors for worsening: need for supplemental oxygen, age 75 years, age between 60 and 74 years and presence of at least one co-morbidity. Severely ill patients requiring oxygen therapy >3 L/min or intensive care were excluded. Eligible patients were randomized in a 1:1 ratio to receive either 800 mg hydroxychloroquine on day 0 followed by 400 mg per day for 8 days or a placebo. The primary end point was a composite of death or start of invasive mechanical ventilation within 14 days following randomization. Secondary end points included mortality and clinical evolution at days 14 and 28, and viral shedding at days 5 and 10. Results: The trial was stopped after 250 patients were included because of a slowing down of the pandemic in France. The intention-to-treat population comprised 123 and 124 patients in the placebo and hydroxychloroquine groups, respectively. The median age was 77 years (interquartile range 58-86 years) and 151/250 (60.4%) patients required oxygen therapy. The primary end point occurred in 9/124 (7.3%) patients in the hydroxychloroquine group and 8/123 (6.5%) patients in the placebo group (relative risk 1.12; 95% CI 0.45e2.80). The rates of positive SARS-CoV-2 RT-PCR tests at days 5 and 10 were 72.8% (75/103) and 57.1% (52/91) in the hydroxychloroquine group, versus 73.0% (73/100) and 56.6% (47/83) in the placebo group, respectively. No difference was observed between the two groups in any of the other secondary end points. Conclusion: In this underpowered trial involving mainly older patients with mild to moderate COVID-19, patients treated with hydroxychloroquine did not experience better clinical or virological outcomes than those receiving the placebo.

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Fichiers liés : Dubee2021Eq06.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/01/2020
• Auteurs : Eloïse GiabicaniMarjolaine WillemsVirginie SteunouSandra Chantot-BastaraudNathalie ThibaudWalid Abi HabibSalah AzziBich LamLaurence BérardHélène Bony-TrifunovicCécile BrachetElise Brischoux-BoucherEmmanuelle CaldaguesRégis CoutantMarie-Laure CuvelierGeorges GelwaneIsabelle GuemasMuriel HouangBertrand IsidorClaire JeandelJames LespinasseCatherine Naud-SaudreauMonique Jesuran-PerelroizenLaurence PerrinJuliette C PiardClaire SechterPierre-François SouchonCaroline StoreyDomitille ThomasY. Le BoucSylvie RossignolIrène NetchineFrédéric Brioude
• Organismes : Sorbonne Université Centre de Recherche Saint-Antoine CHU Trousseau [APHP] CHU Montpellier = Montpellier University Hospital Centre de Recherche Saint-Antoine CHU Trousseau [APHP] CHU Trousseau [APHP] Maladies génétiques d'expression pédiatrique CHU Trousseau [APHP] Centre de Recherche Saint-Antoine Centre de Recherche Saint-Antoine Centre de Recherche Saint-Antoine CHU Trousseau [APHP] CHU Amiens-Picardie Children's University Hospital Queen Fabiola [Bruxelles, Belgium] Université de Franche-Comté Centre Hospitalier Régional Universitaire de Besançon Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Hospitalier Universitaire d'Angers Centre Hospitalier de Calais Hôpital Robert Debré Paris Université Paris Diderot - Paris 7 Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Sorbonne Université CHU Trousseau [APHP] Centre de Recherche Saint-Antoine Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Hospitalier Régional Universitaire [Montpellier] Centre Hospitalier Métropole Savoie [Chambéry] CH Bretagne Sud Association Française des Pédiatres Endocrinologues Libéraux Université Paris Diderot - Paris 7 Hôpital Robert Debré Université de Franche-Comté Centre Hospitalier Régional Universitaire de Besançon Université de Franche-Comté Centre Hospitalier Régional Universitaire de Besançon Hôpital universitaire Robert Debré [Reims] AP-HP Hôpital universitaire Robert-Debré [Paris] Université Paris Diderot - Paris 7 Centre de Recherche Saint-Antoine Centre de Recherche Saint-Antoine Sorbonne Université Hôpitaux Universitaires de Strasbourg Laboratoire de Génétique Médicale Centre de Recherche Saint-Antoine Sorbonne Université CHU Trousseau [APHP] Centre de Recherche Saint-Antoine Sorbonne Université CHU Trousseau [APHP]
• Publié dans Journal of Medical Genetics le 26/10/2020

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Résumé : BACKGROUND: The type 1 insulin-like growth factor receptor (IGF1R) is a keystone of fetal growth regulation by mediating the effects of IGF-I and IGF-II. Recently, a cohort of patients carrying an IGF1R defect was described, from which a clinical score was established for diagnosis. We assessed this score in a large cohort of patients with identified IGF1R defects, as no external validation was available. Furthermore, we aimed to develop a functional test to allow the classification of variants of unknown significance (VUS) in vitro. METHODS: DNA was tested for either deletions or single nucleotide variant (SNV) and the phosphorylation of downstream pathways studied after stimulation with IGF-I by western blot analysis of fibroblast of nine patients. RESULTS: We detected 21 IGF1R defects in 35 patients, including 8 deletions and 10 heterozygous, 1 homozygous and 1 compound-heterozygous SNVs. The main clinical characteristics of these patients were being born small for gestational age (90.9%), short stature (88.2%) and microcephaly (74.1%). Feeding difficulties and varying degrees of developmental delay were highly prevalent (54.5%). There were no differences in phenotypes between patients with deletions and SNVs of IGF1R. Functional studies showed that the SNVs tested were associated with decreased AKT phosphorylation. CONCLUSION: We report eight new pathogenic variants of IGF1R and an original case with a homozygous SNV. We found the recently proposed clinical score to be accurate for the diagnosis of IGF1R defects with a sensitivity of 95.2%. We developed an efficient functional test to assess the pathogenicity of SNVs, which is useful, especially for VUS.

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Fichiers liés : Giabicani et al. - 2019 - Increasing knowledge in IGF1R defects lessons fro.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/01/2020
• Auteurs : Anne-Sophie JourdainFlorence PetitMarie-Françoise OdouMalika BalduyckPerrine BrunelleWilliam DufourSimon BoussionElise Brischoux-BoucherCindy ColsonAnne DieuxMarion GérardJamal GhoumidFabienne GiulianoAlice GoldenbergPhilippe KHAU VAN KIENDaphné LehalleGilles MorinSébastien MouttonThomas SmolClémence VanlerbergheSylvie Manouvrier-HanuFabienne Escande
• Organismes : Centre Hospitalier Régional Universitaire [CHU Lille] Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 Centre Hospitalier Régional Universitaire [CHU Lille] Centre Hospitalier Régional Universitaire [CHU Lille] Service de Biochimie et Biologie Moléculaire Centre Hospitalier Régional Universitaire [CHU Lille] Service de Biochimie et Biologie Moléculaire Pôle de Biologie Pathologie Génétique [CHU Lille] Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 Pôle de Biologie Pathologie Génétique [CHU Lille] Pôle de Biologie Pathologie Génétique [CHU Lille] Centre de génétique humaine [CHRU Besançon] Service de Génétique [CHU Caen] Biologie, génétique et thérapies ostéoarticulaires et respiratoires Pôle de Biologie Pathologie Génétique [CHU Lille] Service de Génétique [CHU Caen] Biologie, génétique et thérapies ostéoarticulaires et respiratoires Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 Pôle de Biologie Pathologie Génétique [CHU Lille] Dpt génétique médicale [CHU Nice] Service de génétique [Rouen] Unité de génétique médicale et cytogénétique Equipe GAD (LNC - U1231) Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon) Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon) Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon) Centre Hospitalier Régional Universitaire [CHU Lille] Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 Pôle de Biologie Pathologie Génétique [CHU Lille] Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 Pôle de Biologie Pathologie Génétique [CHU Lille] Centre Hospitalier Régional Universitaire [CHU Lille]
• Publié dans Human Mutation le 26/10/2020

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Résumé : Congenital limb malformations (CLM) comprise many conditions affecting limbs and more than 150 associated genes have been reported. Due to this large heterogeneity, a high proportion of patients remains without a molecular diagnosis. In the last two decades, advances in high throughput sequencing have allowed new methodological strategies in clinical practice. Herein, we report the screening of 52 genes/regulatory sequences by multiplex high-throughput targeted sequencing, in a series of 352 patients affected with various CLM, over a 3-year period of time. Patients underwent a clinical triage by expert geneticists in CLM. A definitive diagnosis was achieved in 35.2% of patients, the yield varying considerably, depending on the phenotype. We identified 112 single nucleotide variants and 26 copy-number variations, of which 52 are novel pathogenic or likely pathogenic variants. In 6% of patients, variants of uncertain significance have been found in good candidate genes. We showed that multiplex targeted high-throughput sequencing works as an efficient and cost-effective tool in clinical practice for molecular diagnosis of congenital limb malformations. Careful clinical evaluation of patients may maximize the yield of CLM panel testing.

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Fichiers liés : Jourdain_humu_2019.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/01/2020
• Auteurs : Jonathan BoucherAnnie-Claire BalandreMarjolaine DebantJustine VixThomas HarnoisNicolas BourmeysterÉlodie PéraudeauAmandine DesetteJonathan ClarhautFrançoise DebiaisArnaud MonvoisinLaurent Cronier
• Organismes : Signalisation et Transports Ioniques Membranaires Signalisation et Transports Ioniques Membranaires Signalisation et Transports Ioniques Membranaires Signalisation et Transports Ioniques Membranaires Centre hospitalier universitaire de Poitiers = Poitiers University Hospital Signalisation et Transports Ioniques Membranaires Signalisation et Transports Ioniques Membranaires Centre hospitalier universitaire de Poitiers = Poitiers University Hospital Institut de chimie des milieux et matériaux de Poitiers [UMR 7285] Laboratoire de neurosciences expérimentales et cliniques [U 1084] Centre hospitalier universitaire de Poitiers = Poitiers University Hospital Centre hospitalier universitaire de Poitiers = Poitiers University Hospital Institut de chimie des milieux et matériaux de Poitiers [UMR 7285] Signalisation et Transports Ioniques Membranaires Centre hospitalier universitaire de Poitiers = Poitiers University Hospital Signalisation et Transports Ioniques Membranaires Signalisation et Transports Ioniques Membranaires
• Publié dans Cancers le 21/10/2020

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Résumé : Among the different interacting molecules implicated in bone metastases, connexin43 (Cx43) may increase sensitivity of prostate cancer (PCa) cells to bone microenvironment, as suggested by our in silico and human tissue samples analyses that revealed increased level of Cx43 expression with PCa progression and a Cx43 specific expression in bone secondary sites. The goal of the present study was to understand how Cx43 influences PCa cells sensitivity and aggressiveness to bone microenvironment. By means of Cx43-overexpressing PCa cell lines, we revealed a Cx43-dependent promigratory effect of osteoblastic conditioned media (ObCM). This effect on directional migration relied on the presence of Cx43 at the plasma membrane and not on gap junctional intercellular communication and hemichannel functions. ObCM stimulation induced Rac1 activation and Cx43 interaction with cortactin in protrusions of migrating PCa cells. Finally, by transfecting two different truncated forms of Cx43 in LNCaP cells, we determined that the carboxy terminal (CT) part of Cx43 is crucial for the responsiveness of PCa cells to ObCM. Our study demonstrates that Cx43 level and its membrane localization modulate the phenotypic response of PCa cells to osteoblastic microenvironment and that its CT domain plays a pivotal role.

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Fichiers liés : Cx43 Present at the Leading Edge Membrane Governs.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/01/2020
• Auteurs : Jc BenitezMe BoucherE DansinM KerjouanI Bigay-GameE PichonF ThillaysPierre-Emmanuel FalcozS LyubimovaY OulkhouirF CalcagnoL ThibervilleC Clement-DucheneF MorinP MissyP ThomasJ MauryT MolinaN GirardB Besse
• Organismes : Nanomédecine Régénérative
• Publié dans Annals of Oncology le 26/10/2020

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