Philippe JEAN-PIERRE

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• Type de publi. : Article dans une revue
• Date de publi. : 08/08/2023
• Auteurs : Anne-Sophie MichalletR Émi LetestuMagali Le Garff-TavernierLydia CamposMichel TicchioniMarie-Sarah DilhuydyStephane MorissetValérie RouilleBéatrice MahéKamel LaribiBruno VillemagneEmmanuelle FerrantOlivier TournilhacAlain DelmerLysiane MolinaVéronique LeblondCécile TomowiakSophie de GuibertFrederique Orsini-PiocelleAnne BanosPhilippe CarassouGuillaume CartronLuc Mathieu ForneckerLoic YsebaertCaroline DartigeasMargot Truchan-GraczykJean-Pierre VilqueThérèse Aurran SchleinitzFlorence CymbalistaStéphane LeprêtreVincent LévyFlorence Nguyen-KhacPierre Feugier
• Organismes : Centre Léon Bérard [Lyon] Groupe Hospitalier Hôpitaux Universitaires Paris Seine-Saint-Denis [Bobigny] Assistance publique - Hôpitaux de Paris (AP-HP) Centre de Recherche des Cordeliers CHU Pitié-Salpêtrière [AP-HP] Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] Centre Hospitalier Universitaire de Nice Centre Hospitalier Universitaire de Bordeaux Hôpital Edouard Herriot [CHU - HCL] CHU Montpellier = Montpellier University Hospital Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Hospitalier Le Mans (CH Le Mans) Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL] CHU Clermont-Ferrand Hôpital universitaire Robert Debré [Reims] CHU de Grenoble-Alpes - Centre Hospitalier Universitaire CHU Grenoble CHU Pitié-Salpêtrière [AP-HP] Centre hospitalier universitaire de Poitiers = Poitiers University Hospital Service d'hématologie clinique Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois] Centre Hospitalier de la Côte Basque Service d'hématologie [CHR Metz-Thionville] CHU Montpellier = Montpellier University Hospital Centre Hospitalier Universitaire [Strasbourg] Centre de Recherches en Cancérologie de Toulouse Service Hématologie - IUCT-Oncopole [CHU Toulouse] Centre Hospitalier Régional Universitaire de Tours Centre Hospitalier Universitaire d'Angers Institut d'Hématologie de Basse-Normandie Service d’Hématologie [Institut Paoli Calmettes, Marseille] Service d'hématologie biologique [Avicenne] Groupe Hospitalier Hôpitaux Universitaires Paris Seine-Saint-Denis [Bobigny] Cancer and Brain Genomics Service d'hématologie [CRLCC Henri Becquerel] Université de Rouen Normandie Hôpital Avicenne [AP-HP] Groupe Hospitalier Hôpitaux Universitaires Paris Seine-Saint-Denis [Bobigny] CHU Pitié-Salpêtrière [AP-HP] Centre Hospitalier Régional Universitaire de Nancy
• Publié dans Blood Advances le 24/10/2020

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Résumé : n previously untreated, medically fit patients with chronic lymphocytic leukemia (CLL), research is focused on developing fixed-duration strategies to improve long-term outcomes while sparing patients from serious toxicities. The ICLL-07 trial evaluated a fixed-duration (15-month) immunochemotherapy approach in which after obinutuzumab-ibrutinib induction for 9 months, patients (n = 10) in complete remission (CR) with bone marrow (BM) measurable residual disease (MRD) <0.01% continued only ibrutinib 420 mg/day for 6 additional months (I arm), whereas the majority (n = 115) received up to 4 cycles of fludarabine/cyclophosphamide-obinutuzumab 1000 mg alongside the ibrutinib (I-FCG arm). Primary analysis at month 16 showed that 84 of 135 (62.2%) patients enrolled achieved CR with a BM MRD <0.01%. Here, we report follow-up at median 63 months. Peripheral blood (PB) MRD was assessed 6 monthly beyond the end of treatment using a highly sensitive (10-6) flow cytometry technique. In the I-FCG arm, the PB MRD <0.01% rate (low-level positive <0.01% or undetectable with limit of detection ≤10-4) in evaluable patients was still 92.5% (74/80) at month 40 and 80.6% (50/62) at month 64. No differences in the PB MRD status were apparent per to the IGHV mutational status. In the overall population, 4-year progression-free and overall survival rates were 95.5% and 96.2%, respectively. Twelve deaths occurred overall. Fourteen serious adverse events occurred beyond the end of treatment. Thus, our fixed-duration immunochemotherapy approach produced deep and sustained PB MRD responses, high survival rates, and low long-term toxicity. A randomized trial is needed to compare our immunochemotherapy approach with a chemotherapy-free strategy. This trial was registered at www.clinicaltrials.gov as #NCT02666898.

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Fichiers liés : Michallet_&_al.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 08/08/2023
• Auteurs : Marianne MazevetAnissa BelhadefMaxance RibeiroDelphine DaydeAnna LlachMarion LaudetteTiphaine BellevillePhilippe MateoMélanie GressetteFlorence LefebvreJu ChenChristilla Bachelot-LozaCatherine Rucker-MartinFrank LezoualchBertrand CrozatierJean Pierre BenitahMarie-Catherine VozeninRodolphe FischmeisterAna María GomezChristophe LemaireÉric Morel
• Organismes : Signalisation et physiopathologie cardiovasculaire Signalisation et physiopathologie cardiovasculaire Signalisation et physiopathologie cardiovasculaire Signalisation et physiopathologie cardiovasculaire Signalisation et physiopathologie cardiovasculaire Institut des Maladies Métaboliques et Cardiovasculaires Cohortes épidémiologiques en population Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis Signalisation et physiopathologie cardiovasculaire Signalisation et physiopathologie cardiovasculaire Signalisation et physiopathologie cardiovasculaire Cohortes épidémiologiques en population Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis Université Paris-Saclay Hypertension pulmonaire : physiopathologie et innovation thérapeutique Institut des Maladies Métaboliques et Cardiovasculaires Signalisation et physiopathologie cardiovasculaire Signalisation et physiopathologie cardiovasculaire Signalisation et physiopathologie cardiovasculaire Signalisation et physiopathologie cardiovasculaire Signalisation et physiopathologie cardiovasculaire Signalisation et physiopathologie cardiovasculaire UFR Sciences de la santé Simone Veil Signalisation et physiopathologie cardiovasculaire
• Publié dans eLife le 23/10/2020

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Résumé : Anthracyclines, such as doxorubicin (Dox), are widely used chemotherapeutic agents for the treatment of solid tumors and hematologic malignancies. However, they frequently induce cardiotoxicity leading to dilated cardiomyopathy and heart failure. This study sought to investigate the role of the exchange protein directly activated by cAMP (EPAC) in Dox-induced cardiotoxicity and the potential cardioprotective effects of EPAC inhibition. We show that Dox induces DNA damage and cardiomyocyte cell death with apoptotic features. Dox also led to an increase in both cAMP concentration and EPAC1 activity. The pharmacological inhibition of EPAC1 (with CE3F4) but not EPAC2 alleviated the whole Dox-induced pattern of alterations. When administered in vivo, Dox-treated WT mice developed a dilated cardiomyopathy which was totally prevented in EPAC1 knock-out (KO) mice. Moreover, EPAC1 inhibition potentiated Dox-induced cell death in several human cancer cell lines. Thus, EPAC1 inhibition appears as a potential therapeutic strategy to limit Dox-induced cardiomyopathy without interfering with its antitumoral activity.

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Fichiers liés : elife-83831-v3.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 08/08/2023
• Auteurs : Achraf BennisPhilippe LeleuxAlban CanaliCaroline De PourtalesSandrine MouyssetDavid SimonciniPierre BroussetFrancois-Xavier FrenoisChristian RecherJean-Marc AlliotJean-Baptiste RieuSarah Bertoli
• Organismes : Real Expression Artificial Life Algorithmes Parallèles et Optimisation Institut Universitaire du Cancer de Toulouse - Oncopole Algorithmes Parallèles et Optimisation Algorithmes Parallèles et Optimisation Algorithmes Parallèles et Optimisation Real Expression Artificial Life Institut Universitaire du Cancer de Toulouse - Oncopole Institut Universitaire du Cancer de Toulouse - Oncopole Institut Universitaire du Cancer de Toulouse - Oncopole Algorithmes Parallèles et Optimisation Centre Hospitalier Universitaire de Toulouse Institut Universitaire du Cancer de Toulouse - Oncopole Institut Universitaire du Cancer de Toulouse - Oncopole
• Publié dans HemaSphere le 26/10/2020

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Résumé : Background: The assessment of bone marrow (BM) cells is a central component for the diagnosis of AML. However, the manual assessment of BMS and counting of differentiated cells is a time-consuming method that depends on the experience and abilities of cytomorphologists and is not fully reproducible.Aims: In this study, we develop a pipeline for the automatic segmentation and classification of cells from BMS of patients with AML using Machine Learning (ML) and Computer Vision techniques.Methods: Whole BMS slides from 647 patients diagnosed with AML between 1/2017 and 12/2020 in Toulouse University Hospital were numerized using Panoramic 250 Flash II (3DHISTECH) scanner to obtain high-definition pictures in a.MRXS format, providing multiple magnification levels whose highest corresponds to 823 X (121nm/pixel). To analyze BMS images, we designed a pipeline separated into 3 steps as described below: first, we pre-selected tiles at the deepest zoom level most likely to contain exploitable cells to define areas of interest (AOI). For this purpose, we proposed a two-tier approach to filter fixed-size tiles on two zoom levels consecutively, using a combination of a pixel-wise k-means method and decision trees using textural features. Second, we extracted BM cells from the AOI. In this step, we considered two approaches: segmentation with an in-house segmentation software, which implements a genetic algorithm to find the cells, and a deep-learning-based model called Faster-RCNN, used for cell detection in the state-of-the-art. The former method only requires a low number of annotated images to train, but the training of the second one is much faster. In the third and final step, we combined the computation of radiomics features with ML methods to classify the extracted single cell images in a semi-supervised and unsupervised manner.Results: We were able to design a pipeline allowing automatic BM cell segmentation and classification, to identify between 1k and 1.5k cells from each BMS. At a lower magnification, we were also able to design a pipeline to identify megakaryocytes. We will show the entire multi-step pipeline and examples of automatically extracted and classified cells.Summary/Conclusion: Running our AI-based pipeline shows encouraging results in terms of extraction and classification of cells from BMS of AML. Our work will lead to the development of an AI tool to support cytomorphologists in the assessment of BMS from patients with AML. It will also permit the constitution of an AML bone marrow cells library

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• Type de publi. : Article dans une revue
• Date de publi. : 08/08/2023
• Auteurs : David SiniscalcoLaurence PessoniLaurent BillonAnne BoussonniereAnne-Sophie CastanetJean-François BardeauPierre NickmilderPhilippe LeclèreN. Delorme
• Organismes : Institut des Molécules et Matériaux du Mans Institut des sciences analytiques et de physico-chimie pour l'environnement et les materiaux Institut des sciences analytiques et de physico-chimie pour l'environnement et les materiaux Institut des Molécules et Matériaux du Mans Institut des Molécules et Matériaux du Mans Institut des Molécules et Matériaux du Mans Laboratory for Physics of Nanomaterials and Energy Laboratory for Physics of Nanomaterials and Energy Institut des Molécules et Matériaux du Mans
• Publié dans ACS Applied Polymer Materials le 24/10/2020

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Résumé : The ability to observe photoinduced reversible solid-to-liquid transitions for some polymers bearing photo-active azobenzene groups (azopolymers) has become a competitive research field in materials science and technology because of their potential applications in photocontrolled adhesives, photohealable materials, or soft lithography. Unfortunately, methods to accurately characterize this transition are scarce and mainly qualitative, which limits the understanding of the parameters governing it. In the first part of this paper, we will show that the photoinduced reversible solid-to-liquid transition can be associated to a transition temperature (named TSL). This transition temperature can be accurately measured using a scanning probe microscopy-based method. Then, the measurement of TSL on azopolymers with different chemical structures will allow us to understand why the experimental irradiation conditions to observe the solid-to-liquid transition were different. With the possibility to accurately characterize the photoinduced solid-to-liquid transition, we believe that this work paves the way to the optimization of azopolymer design for a better photocontrol of their mechanical properties.

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• Type de publi. : Article dans une revue
• Date de publi. : 08/08/2023
• Auteurs : Vassili PanagidesGuillermo CuervoJaume LlopisMohamed Abdel-WahabNorman MangnerGilbert HabibAnder RegueiroCarlos MestresPilar TornosEric DurandChristine Selton-SutyNikolaj IhlemannNiels BruunMarina UrenaEnrico CecchiHolger ThieleEmanuele Durante-MangoniCostanza PellegriniHelene EltchaninoffEugene AthanLars SøndergaardAxel LinkePierre TattevinDavid del ValEduard QuintanaVivian ChuJosep Rodés-CabauJosé M MiróLiliana ClaraMarisa SanchezJosé CasabéClaudia CortesFrancisco NacinovichPablo Fernandez OsesRicardo RonderosAdriana SucariJorge ThiererJavier AltclasSilvia KoganDenis SpelmanEugene AthanOwen HarrisKarina KennedyRen TanDavid GordonLito PapanicolasTony KormanDespina KotsanasRobyn DeverPhillip JonesPam KonecnyRichard LawrenceDavid ReesSuzanne RyanMichael FeneleyJohn HarknessPhillip JonesSuzanne RyanPhillip JonesSuzanne RyanPhillip JonesJeffrey PostPorl ReinbottSuzanne RyanRainer GattringerFranz WiesbauerAdriana Ribas AndradeAna Cláudia Passos de BritoArmenio Costa GuimarãesMax GrinbergAlfredo José MansurRinaldo Focaccia SicilianoTania Mara Varejao StrabelliMarcelo Luiz Campos VieiraRegina Aparecida de Medeiros TranchesiMarcelo Goulart PaivaClaudio Querido FortesAuristela de Oliveira RamosClara WekslerGiovanna FerraiuoliWilma GolebiovskiCristiane LamasJames KarlowskyYoav KeynanAndrew MorrisEthan RubinsteinSandra Braun JonesPatricia GarciaM CerecedaAlberto FicaRodrigo Montagna MellaRicardo FernandezLiliana FrancoJavier GonzalezAstrid Natalia JaramilloBruno BarsicSuzana BukovskiVladimir KrajinovicAna PangercicIgor RudezJosip VinceljTomas FreibergerJiri PolBarbora ZaloudikovaZainab AshourAmani El KholyMarwa MishaalDina OsamaHussien RizkNeijla AissaCorentine AlauzetFrançois AllaCatherine CampagnacThanh Doco-LecompteChristine Selton-SutyJean-Paul CasaltaPierre-Edouard FournierGilbert HabibDidier RaoultFranck ThunyFrancois DelahayeArmelle DelahayeFrancois VandeneschErwan DonalPierre Yves DonnioErwan FlecherChristian MicheletMatthieu RevestFlorent ChevalierAntoine JeuJean-Paul RemadiDan RusinaruChristophe TribouilloyYvette BernardCatherine ChirouzeBruno HoenJoel LeroyPatrick PlésiatChristoph NaberCarl NeuerburgBahram MazaheriChristoph NaberCarl NeuerburgSophia AthanasiaIoannis DeliolanisHelen GiamarellouTsaganos ThomasEfthymia GiannitsiotiElena MylonaOlga PaniaraKonstantinos PapanicolaouJohn PyrosAthanasios SkoutelisElena MylonaOlga PaniaraKonstantinos PapanikolaouJohn PyrosAthanasios SkoutelisGautam SharmaJohnson FrancisLathi NairVinod ThomasKrishnan VenugopalMargaret HannanJohn HurleyMaor WanounouDan GilonSarah IsraelMaya KoremJacob StrahilevitzEthan RubinsteinJacob StrahilevitzEmanuele Durante-MangoniDomenico IossaSerena OrlandoMaria Paola UrsiPia Clara PafundiFabiana D’amicoMariano BernardoSusanna CuccurulloGiovanni DialettoFranco Enrico CovinoSabrina ManducaAlessandro Della CorteMarisa de FeoMarie Françoise TripodiEnrico CecchiFrancesco de RosaDavide FornoMassimo ImazioRita TrincheroPaolo GrossiMariangela LattanzioAntonio TonioloAntonio GoglioAnnibale RaglioVeronica RavasioMarco RizziFredy SuterGiampiero CarosiSilvia MagriLiana SignoriniZeina KanafaniSouha KanjAhmad Sharif-YakanImran AbidinSyahidah Syed TaminEduardo Rivera MartínezGabriel Israel Soto NietoJan van der MeerStephen ChambersDavid HollandArthur MorrisNigel RaymondKerry ReadDavid MurdochStefan DragulescuAdina IonacCristian MornosO ButkevichNatalia ChipiginaOzerecky KirillKulichenko VadimTatiana VinogradovaJameela EdathoduMagid HalimYee-Yun LiewRu-San TanTatjana Lejko-ZupancMateja LogarManica Mueller-PremruPatrick CommerfordAnita CommerfordEduan DeetlefsCass HansaMpiko NtsekheManel AlmelaJuan AmbrosioniManuel AzquetaMerce BrunetPedro CastroElisa de LazzariCarlos FalcesDavid FusterGuillermina FitaCristina Garcia- De- La- MariaJavier Garcia-GonzalezJose GatellJaume LlopisFrancesc MarcoJosé MiróAsuncion MorenoJosé OrtizSalvador NinotJ Carlos ParéJuan PericasEduard QuintanaJose RamirezIrene RoviraElena SandovalMarta SitgesAdrian TellezJosé TolosanaBarbara VidalJordi VilaIgnasi AngueraBernat FontJoan Raimon GumaJavier BermejoEmilio BouzaMiguel Angel Garcia FernándezVictor Gonzalez-RamalloMercedes MarínPatricia MuñozMiguel PedromingoJorge RodaMarta Rodríguez-CréixemsJorge SolisBenito AlmiranteNuria Fernandez-HidalgoPilar TornosArístides de AlarcónRicardo ParraEric AlestigMagnus JohanssonLars OlaisonUlrika Snygg-MartinOrathai PachiratPimchitra PachiratBurabha PussadhammaVichai SenthongAnna CaseyTom ElliottPeter LambertRichard WatkinChristina EytonJohn KleinSuzanne BradleyCarol KauffmanRoger BedimoVivian ChuG Ralph CoreyAnna Lisa CrowleyPamela DouglasLaura DrewVance FowlerThomas HollandTahaniyat LalaniDaniel MudrickZaniab SamadDaniel SextonMartin StryjewskiAndrew WangChristopher WoodsStamatios LerakisRobert CanteyLisa SteedDannah WrayStuart DickermanHector BonillaJoseph DipersioSara-Jane SalstromJohn BaddleyMukesh PatelGail PetersonAmy StancovenDonald LevineJonathan RiddleMichael RybakChristopher CabellMohamed Abdel-WahabAlexandre AbizaidGuglielmomario Actis DatoFernando AlfonsoAbdullah AlkhodairAlberto AlperiIgnacio Amat-SantosJulio AndreaVincent AuffretMarco BarbantiAntonio BartorelliMarouane BoukhrisFrancisco Campelo-ParadaJuan Carlos CastilloTarun ChakravartyChekrallah ChamandiAsim CheemaAlexandre Siciliano ColafranceschiValter Correia de LimaLisa CrusiusDavid del ValEric DurandHelene EltchaninoffVinicius EstevesMaria-Cristina FerreiraClaudia FiorinaPhilippe GervaisFrancesco GianniniRoger GodinhoEnrique Gutiérrez-IbanesRosana Hernandez-AntolinHoward HerrmannDominique HimbertDavid HolzheyZenon HuczekOliver HusserNikolaj IhlemannSamir KapadiaUtz KappertWon-Keun KimAnnapoorna KiniSusheel KodaliMartin LandtAzeem LatibHervé Le BretonAxel LinkeJohn LiskoUgolino LiviFrédéric MaesRaj MakkarJose Armando MangioneNorman MangnerMarcos Antonio MarinoJean-Bernard MassonAntonio MiceliErika Munoz-GarciaLuis Nombela-FrancoPaolo OlivaresVassili PanagidesIsaac PascualAnder RegueiroHenrique RibeiroJosep Rodés-CabauRafael RomagueraFrancesco RosatoLuisa SalidoFabio Sandoli de BritoPiotr ScisloVicenç SerraClement ServozSaif SiddiquiJan Malte SinningLars SøndergaardSandro SpongaStefan StorteckyDidier TchetcheLuca TestaMarina UrenaVictoria VilaltaJohn WebbHarindra Wijeysundera
• Organismes : Université Laval [Québec] Universitat de Barcelona Universitat de Barcelona Universität Leipzig = Leipzig University Technische Universität Dresden = Dresden University of Technology Hôpital de la Timone [CHU - APHM] Microbes Evolution Phylogénie et Infections Institut Hospitalier Universitaire Méditerranée Infection University hospital of Zurich [Zurich] Endothélium, valvulopathies et insuffisance cardiaque Service de Cardiologie [CHRU Nancy] Rigshospitalet [Copenhagen, Denmark] AP-HP - Hôpital Bichat - Claude Bernard [Paris] Universität Leipzig = Leipzig University Università degli studi della Campania "Luigi Vanvitelli" = University of the Study of Campania Luigi Vanvitelli Deutsches Herzzentrum München Endothélium, valvulopathies et insuffisance cardiaque Deakin University [Melbourne Burwood] Rigshospitalet [Copenhagen, Denmark] Technische Universität Dresden = Dresden University of Technology Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] ARN bactériens et médecine Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] Universitat de Barcelona Université Laval [Québec] Universitat de Barcelona Instituto de Salud Carlos III [Madrid] Pathogénie des Staphylocoques – Staphylococcal Pathogenesis [CIRI]
• Publié dans Clinical Infectious Diseases le 30/10/2020

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Résumé : Background: Scarce data are available comparing infective endocarditis (IE) following surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). This study aimed to compare the clinical presentation, microbiological profile, management, and outcomes of IE after SAVR vs. TAVR.Methods: Data were collected from the "Infectious Endocarditis after TAVR International" (enrollment from 2005 to 2020) and the "International Collaboration on Endocarditis" enrollment from 2000 to 2012) registries. Only patients with an IE affecting the aortic valve prosthesis were included. A 1:1 paired matching approach was used to compare patients with TAVR and SAVR.Results: A total of 1688 patients were included. Of them, 602 (35.7%) had a surgical bioprosthesis (SB), 666 (39.5%) a mechanical prosthesis, 70 (4.2%) a homograft, and 350 (20.7%) a transcatheter heart valve. In the SAVR vs. TAVR matched population, the rate of new moderate or severe aortic regurgitation was higher in the SB group (43.4% vs. 13.4%, p < 0.001), and fewer vegetations were diagnosed in the SB group (62.5% vs. 82%, p < 0.001). Patients with a SB had a higher rate of perivalvular extension (47.9% vs.27%, p < 0.001) and Staphylococcus Aureus was less common in this group (13.4% vs. 22%, p = 0.033). Despite a higher rate of surgery in patients with SB (44.4% vs. 26.8%, p < 0.001), 1-year mortality was similar (SB: 46.5%, TAVR: 44.8%, log-rank p = 0.697).Conclusions: Clinical presentation, type of causative microorganism and treatment differed between patients with an IE located on SB compared to TAVR. Despite these differences, both groups exhibited high and similar mortality at 1-year follow-up.

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Fichiers liés : Panagides et al-2023-Infective Endocarditis After Transcatheter versus Surgical Aortic Valve.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/08/2023
• Auteurs : Frédérik OgerCyril BourouhMarika Elsa FrianoEmilie CourtyLaure RollandXavier GromadaMaeva MorenoCharlène CarneyNabil RabhiEmmanuelle DurandSouhila AmanzougareneLionel BerberianMehdi DerhourhiEtienne BlancSarah Anissa HannouPierre-Damien DenechaudZohra BenfoddaPatrick MeffreLluis FajasJulie Kerr-ConteFrançois PattouPhillippe FroguelBenoit PourcetAmelie BonnefondPatrick CollombatJean-Sébastien Annicotte
• Organismes : Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 Institut de Biologie Valrose Université de Lille Institut Pasteur de Lille Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 Boston University School of Medicine EGI Advanced Computing Services for Research Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 Université de Lausanne = University of Lausanne Détection, évaluation, gestion des risques CHROniques et éMErgents (CHROME) - Nîmes Université Détection, évaluation, gestion des risques CHROniques et éMErgents (CHROME) - Nîmes Université Université de Lausanne = University of Lausanne Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 Institut de Biologie Valrose Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167
• Publié dans Diabetes le 01/11/2020

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Résumé : The loss of pancreatic β-cell identity has emerged as an important feature of type 2 diabetes development, but the molecular mechanisms are still elusive. Here, we explore the cell-autonomous role of the cell-cycle regulator and transcription factor E2F1 in the maintenance of β-cell identity, insulin secretion, and glucose homeostasis. We show that the β-cell–specific loss of E2f1 function in mice triggers glucose intolerance associated with defective insulin secretion, altered endocrine cell mass, downregulation of many β-cell genes, and concomitant increase of non–β-cell markers. Mechanistically, epigenomic profiling of the promoters of these non–β-cell upregulated genes identified an enrichment of bivalent H3K4me3/H3K27me3 or H3K27me3 marks. Conversely, promoters of downregulated genes were enriched in active chromatin H3K4me3 and H3K27ac histone marks. We find that specific E2f1 transcriptional, cistromic, and epigenomic signatures are associated with these β-cell dysfunctions, with E2F1 directly regulating several β-cell genes at the chromatin level. Finally, the pharmacological inhibition of E2F transcriptional activity in human islets also impairs insulin secretion and the expression of β-cell identity genes. Our data suggest that E2F1 is critical for maintaining β-cell identity and function through sustained control of β-cell and non–β-cell transcriptional programs.

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Fichiers liés : Manuscrit_29032023_Oger_et_al_final_HAL.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/08/2023
• Auteurs : Caroline MonchaudJean-Baptiste WoillardSabrina CrepinNaïma TafziLudovic MicallefJean-Philippe RerolleSébastien DharancyFilomena ContiGabriel ChoukrounAntoine ThierryMatthias BüchlerEphrem SalaméCyril GarrousteChristophe DuvouxCharlotte ColosioPierre MervilleDany AnglicheauIsabelle EtienneFaouzi SalibaChristophe MariatMarilyne Debette-GratienPierre Marquet
• Organismes : Pharmacologie et Transplantation CHU Limoges Fédération Hospitalo-Universitaire « SUrvival oPtimization in ORgan Transplantation » Pharmacologie et Transplantation CHU Limoges Fédération Hospitalo-Universitaire « SUrvival oPtimization in ORgan Transplantation » Service de Pharmacologie, toxicologie et pharmacovigilance [CHU Limoges] Fédération Hospitalo-Universitaire « SUrvival oPtimization in ORgan Transplantation » Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation CHU Limoges Fédération Hospitalo-Universitaire « SUrvival oPtimization in ORgan Transplantation » Service de Néphrologie, Dialyse, Transplantations [CHU Limoges] Fédération Hospitalo-Universitaire « SUrvival oPtimization in ORgan Transplantation » Hôpital Claude Huriez [Lille] Institute for Translational Research in Inflammation - U 1286 CHU Pitié-Salpêtrière [AP-HP] Service de Néphrologie-Dialyse-Transplantation [CHU Amiens-Picardie] Mécanismes physiopathologiques et conséquences des calcifications cardiovasculaires - UR UPJV 7517 Centre hospitalier universitaire de Poitiers = Poitiers University Hospital Fédération Hospitalo-Universitaire « SUrvival oPtimization in ORgan Transplantation » Service de néphrologie et immunologie clinique [CHRU Tours] Centre Hospitalier Régional Universitaire de Tours Fédération Hospitalo-Universitaire « SUrvival oPtimization in ORgan Transplantation » CHU Clermont-Ferrand CHU Henri Mondor [Créteil] Université de Reims Champagne-Ardenne Centre Hospitalier Universitaire de Bordeaux UFR Médecine [Santé] - Université Paris Cité Service Néphrologie et transplantation rénale Adultes [CHU Necker] CHU Rouen Physiopathologie et traitement des maladies du foie Centre Hépato-Biliaire [Hôpital Paul Brousse] Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] Fédération Hospitalo-Universitaire « SUrvival oPtimization in ORgan Transplantation » Pharmacologie et Transplantation Fédération Hospitalo-Universitaire « SUrvival oPtimization in ORgan Transplantation »
• Publié dans Transplant International le 25/10/2020

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Résumé : LCP-tacrolimus displays enhanced oral bioavailability compared to immediate-release (IR-) tacrolimus. The ENVARSWITCH study aimed to compare tacrolimus AUC in stable kidney (KTR) and liver transplant recipients (LTR) on IR-tacrolimus converted to LCP-tacrolimus, in order to re-evaluate the 1:0.7 dose ratio recommended in the context of a switch and the efficiency of the subsequent dose adjustment. Tacrolimus AUC was obtained by Bayesian estimation based on three concentrations measured in dried blood spots before (V2), after the switch (V3), and after LCP-tacrolimus dose adjustment intended to reach the pre-switch AUC (V4). AUC estimates and distributions were compared using the bioequivalence rule for narrow therapeutic range drugs (Westlake 90% CI within 0.90-1.11). Fifty-three KTR and 48 LTR completed the study with no major deviation. AUC bioequivalence was met in the entire population and in KTR between V2 and V4 and between V2 and V3. In LTR, the Westlake 90% CI was close to the acceptance limits between V2 and V4 (90% CI = [0.96-1.14]) and between V2 and V3 (90% CI = [0.96-1.15]). The 1:0.7 dose ratio is convenient for KTR but may be adjusted individually for LTR. The combination of DBS and Bayesian estimation for tacrolimus dose adjustment may help with reaching appropriate exposure to tacrolimus rapidly after a switch.

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Fichiers liés : Tacrolimus Exposure Before and After a Switch From Twice-Daily Immediate-Release to Once-Daily Prolonged Release Tacrolimus.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/08/2023
• Auteurs : Frédérik OgerCyril BourouhMarika Elsa FrianoEmilie CourtyLaure RollandXavier GromadaMaeva MorenoCharlène CarneyNabil RabhiEmmanuelle DurandSouhila AmanzougareneLionel BerberianMehdi DerhourhiEtienne BlancSarah Anissa HannouPierre-Damien DenechaudZohra BenfoddaPatrick MeffreLluis FajasJulie Kerr-ConteFrançois PattouPhillippe FroguelBenoit PourcetAmelie BonnefondPatrick CollombatJean-Sébastien Annicotte
• Organismes : Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 Université de Lille Institut Pasteur de Lille Centre Hospitalier Régional Universitaire [CHU Lille] Institut National de la Santé et de la Recherche Médicale
• Publié dans Diabetes le 01/11/2020

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Résumé : The loss of pancreatic β-cell identity has emerged as an important feature of type 2 diabetes development, but the molecular mechanisms are still elusive. Here, we explore the cell-autonomous role of the cell-cycle regulator and transcription factor E2F1 in the maintenance of β-cell identity, insulin secretion, and glucose homeostasis. We show that the β-cell–specific loss of E2f1 function in mice triggers glucose intolerance associated with defective insulin secretion, altered endocrine cell mass, downregulation of many β-cell genes, and concomitant increase of non–β-cell markers. Mechanistically, epigenomic profiling of the promoters of these non–β-cell upregulated genes identified an enrichment of bivalent H3K4me3/H3K27me3 or H3K27me3 marks. Conversely, promoters of downregulated genes were enriched in active chromatin H3K4me3 and H3K27ac histone marks. We find that specific E2f1 transcriptional, cistromic, and epigenomic signatures are associated with these β-cell dysfunctions, with E2F1 directly regulating several β-cell genes at the chromatin level. Finally, the pharmacological inhibition of E2F transcriptional activity in human islets also impairs insulin secretion and the expression of β-cell identity genes. Our data suggest that E2F1 is critical for maintaining β-cell identity and function through sustained control of β-cell and non–β-cell transcriptional programs. Article Highlights β-Cell–specific E2f1 deficiency in mice impairs glucose tolerance. Loss of E2f1 function alters the ratio of α- to β-cells but does not trigger β-cell conversion into α-cells. Pharmacological inhibition of E2F activity inhibits glucose-stimulated insulin secretion and alters β- and α-cell gene expression in human islets. E2F1 maintains β-cell function and identity through control of transcriptomic and epigenetic programs.

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• Type de publi. : Communication dans un congrès
• Date de publi. : 01/08/2023
• Auteurs : Amiaud LionelDaniela Torres-DíazRomain BasalgèteLeo Albert SalaAntoine HacquardJean-Hugues FillionXavier MichautLaurent PhilippeGéraldine FeraudA LafosseMathieu Bertin
• Organismes : Institut des Sciences Moléculaires d'Orsay Institut des Sciences Moléculaires d'Orsay Laboratoire d'Etude du Rayonnement et de la Matière en Astrophysique et Atmosphères = Laboratory for Studies of Radiation and Matter in Astrophysics and Atmospheres Laboratoire d'Etude du Rayonnement et de la Matière en Astrophysique et Atmosphères = Laboratory for Studies of Radiation and Matter in Astrophysics and Atmospheres Institut des Sciences Moléculaires d'Orsay Laboratoire d'Etude du Rayonnement et de la Matière en Astrophysique et Atmosphères = Laboratory for Studies of Radiation and Matter in Astrophysics and Atmospheres Laboratoire d'Etude du Rayonnement et de la Matière en Astrophysique Laboratoire d'Etude du Rayonnement et de la Matière en Astrophysique Laboratoire d'Etude du Rayonnement et de la Matière en Astrophysique et Atmosphères = Laboratory for Studies of Radiation and Matter in Astrophysics and Atmospheres Laboratoire d'Etude du Rayonnement et de la Matière en Astrophysique et Atmosphères = Laboratory for Studies of Radiation and Matter in Astrophysics and Atmospheres Institut des Sciences Moléculaires d'Orsay Laboratoire d'Etude du Rayonnement et de la Matière en Astrophysique et Atmosphères = Laboratory for Studies of Radiation and Matter in Astrophysics and Atmospheres

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• Type de publi. : Article dans une revue
• Date de publi. : 01/08/2023
• Auteurs : Friederike PetzoldKaty BillotXiaoyi ChenCharline HenryEmilie FilholYoann MartinMarina AvramescuMaxime DouilletVincent MorinièrePauline KrugCécile JeanpierreKalman ToryOlivia BoyerAnita BurgunAude ServaisRemi SalomonAlexandre BenmerahLaurence HeidetNicolas GarcelonCorinne AntignacMohamad ZaidanSophie SaunierTania Attié-BitachValerie Comier-DaireIsabelle PerraultYaacov FrishbergBrigitte LlanasMichel BroyerNabil MohsinMarie-Alice MacherNicole PhilipVéronique BaudouinDamian BrackmanChantal LoiratMarina CharbitMaud DehennaultClaude GuyotPierre BatailleMariet EltingGeorges DeschênesAndrea GropmanGeneviève GuestMarie-France GagnadouxPhilippe NicoudPierre CochatBruno RanchinAlbert BensmanAnne-Marie GuerrotBertrand KnebelmannIlmay BilgeDanièle BrunoStéphane BurteyCaroline Rousset RouvièreValérie CaudwellDenis MorinHélène DollfusAnne MaisinChristian HamelÉric BiethSophie GieJudith GoodshipGwenaelle RousseyHermine La SelveHubert NivetLucie BessenayMathilde CaillezJean Bernard PalcouxStéphane BenoîtPhilippe DubotMarc FilaFabienne GiulianoDaouya IfteneMichele KesslerTheresa KwonAnine LahocheAudrey LaurentAnne-Laure LeclercDavid MilfordThomas NeuhausSylvie OdentPhilippe EckartDominique ChauveauPatrick NiaudetHoracio RepettoSophie TaqueAlexandra BruelAlexandra Noel-BotteEmma Allain LaunayLisa AllardDany AnlicheauAnne-Laure AdraArnaud GarnierArvind NagraRemy BaatardJustine BacchettaBanu SadikogluChristine BarneriasAnne BarthelemyLina BaselNader BassiliosHedi Ben MaizFatma Ben MoussaFaïza BenmatiRomain BerthaudAurélia BertholetDominique BlanchierJean Jacques BoffaKarim BouchirebIhab BouhabelZakaria BoukerrouchaGuylhène Bourdat-MichelOdile BouteKarine BrochardRoseline CaumesSiham Chafai ElalaouiBernard ChamontinMarie Caroline ChastangChristine PietrementChristine RicherChristophe LegendreKarin DahanFabienne Dalla-ValeDamien ThibaudinMaxime DauvergneSalandre DavourieMartin DebeukelaerJean Daniel DelbetConstantinos DeltasDenis GraberNadège DevillarsBoucar DioufMartine Doco FenzyJean-Luc AndréDominique JolyAlan FryerLaetitia AlbanoElisabeth CassutoAline PinconAna MedeiraAnnabelle ChaussenotAnne Mensire-MarinierFrancois BouissouStéphane DecramerArmand BottaniAurélie HummelAlexandre KarrasAvi KatzChristine AzemaBénédicte JanbonBernard RousselClaude BonniolChristiophe MariatGérard ChampionDeborah ChantreuilNicolas ChassaingChristiane MoussonChristine BaudeauDelphine Hafdar CuntzCyril MignotLaurene DehouxDidier LacombeThierry HannedoucheElodie MérieauEmmanuelle CharlinEric GauthierFlorent PlasseStanislas FaguerFanny LebasFlorence DemurgerFrancesco EmmaFrançois CartaultGeneviève DumontNathalie GodefroidVincent GuigonisSophie HillaireJaap GroothoffJan DudleyNoémie Jourde-ChicheKhalil El KarouiSaoussen KridKrier CoudertLarbi BencheickLaurent YverMarie-Pierre LavocatLe Monies de SagazanValerie LeroyLise ThibaudinLiz IngulliLorraine GwanmesiaLydie BurglenMarie-Hélène Saïd-MenthonMarta CarreraMathilde NizonCatherine MelanderMichel FoulardMonique BlayoJacques PrinseauNadine JayNathalie BrunNicolas CamilleFrançois NobiliOlivier DevuystOuafa Ben BrahimPaloma ParvexLaurence Perrin SabourinPhilippe BlancPhilippe VanhillePierre GalichonSophie PierrepontVincent PlanquoisGwenaelle PoussardClaire Pouteil NobleRadia AllalRaphaelle BernardRaynaud MounetRémi CahenRenaud TouraineClaire RigothierAmélie RyckewaertMathieu SacquepeeSalima El ChehadehCharlotte SamailleShuman HaqAri SimckesStéphanie LanoiseléeStephanie TellierJean-François SubraSylvie CloarecJulie TenenbamThomas LamyValérie Drouin GarraudHuguette ValetteVanina MeyssonnierRosa Vargas-PoussouYves SnajerSandrine DuraultEmmanuelle PlaisierEtienne BerardFadi FakhouriFerielle LouilletPaul FinielzMichel FischbachBernard FoliguetHélène Francois-PradierFlorentine GaraixMarion GerardGianfranco RizzoniBrigitte Gilbert-DussardierDenis GlotzAstrid Godron DubrasquetJean-Pierre GrünfeldGuillaume BolleeMichelle HallSverker HanssonDamien HayeHélène TaffinFriedhelm HildebrandtMaryvonne HourmandHümya KayseriliIvan TackMarie Line JacquemontJennifer Fabre-TesteCliff KashtanKkoen van HoeckAlexandre KleinYannick KnefatiNine KnoersMartin KonradAlain LachauxIsabelle LandruGilbert LandthalerPhilippe LangPatrick Le PogampTristan LegrisCatherine DidaillerThierry LobbedezLoïc de ParscauLucile PinsonHervé MaheutMarc Duval-ArnouldMarlène RioMarie-Claire GublerPierre MervilleGuillaume MestralletMaite MeunierKarine MoreauJérôme HarambatGraeme MorganGeorges MouradNiksic StuberOdile Boespflug-TanguyOlivier DunandOlivier NielNacera OualiPaolo MalvezziPauline Abou JaoudeSolenne PelletierJulie PeltierM.B. PetersenPhilippe MichelPhilippe RémyJean-Baptiste PhilitValérie PichaultThierry Billette de VillemeurBernard BoudailliezBruno LeheupClaire DossierDjamal DjeddiYves BerlandBruno Hurault de LignySusan RigdenChristophe RobinoAnnick RossiSabine SarnackiMessaoud SaidaniAlbane Brodin SartoriusElise SchäferSztriha LaszloMarie-Christine ThouretAngélique Thuillier-LecoufHoward TrachtmanClaire TrivinMichel TsimaratosRita van Damme-LombaertsMarjolaine WillemsMichel YoussefAriane ZaloszycAlexis ZawodnikMarie-Julia Ziliotis
• Organismes : Laboratoire des Maladies Rénales Héréditaires = Laboratory of Hereditary Kidney Diseases University Hospital Leipzig = Universitätsklinikum Leipzig Laboratoire des Maladies Rénales Héréditaires = Laboratory of Hereditary Kidney Diseases Imagine - Institut des maladies génétiques (IHU) Centre de Recherche des Cordeliers Laboratoire des Maladies Rénales Héréditaires = Laboratory of Hereditary Kidney Diseases Laboratoire des Maladies Rénales Héréditaires = Laboratory of Hereditary Kidney Diseases Laboratoire des Maladies Rénales Héréditaires = Laboratory of Hereditary Kidney Diseases Laboratoire des Maladies Rénales Héréditaires = Laboratory of Hereditary Kidney Diseases Département de Pédiatrie et maladies infectieuses [CHU Necker] Imagine - Institut des maladies génétiques (IHU) Centre de Recherche des Cordeliers Service de génétique moléculaire [CHU Necker] Laboratoire des Maladies Rénales Héréditaires = Laboratory of Hereditary Kidney Diseases Département de Pédiatrie et maladies infectieuses [CHU Necker] Laboratoire des Maladies Rénales Héréditaires = Laboratory of Hereditary Kidney Diseases Semmelweis University [Budapest] Département de Pédiatrie et maladies infectieuses [CHU Necker] Laboratoire des Maladies Rénales Héréditaires = Laboratory of Hereditary Kidney Diseases Centre de Recherche des Cordeliers Service d'informatique médicale et biostatistiques [CHU Necker] Inria Siège Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte [CHU-Necker] Laboratoire des Maladies Rénales Héréditaires = Laboratory of Hereditary Kidney Diseases Département de Pédiatrie et maladies infectieuses [CHU Necker] Laboratoire des Maladies Rénales Héréditaires = Laboratory of Hereditary Kidney Diseases Laboratoire des Maladies Rénales Héréditaires = Laboratory of Hereditary Kidney Diseases Département de Pédiatrie et maladies infectieuses [CHU Necker] Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte [CHU-Necker] Centre de Recherche des Cordeliers Imagine - Institut des maladies génétiques Laboratoire des Maladies Rénales Héréditaires = Laboratory of Hereditary Kidney Diseases Service Néphrologie et transplantation rénale Adultes [CHU Necker] Hôpital Bicêtre [GHU AP-HP. Université Paris-Saclay, Le Kremlin-Bicêtre] Laboratoire des Maladies Rénales Héréditaires = Laboratory of Hereditary Kidney Diseases
• Publié dans Kidney International le 27/10/2020

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Résumé : Nephronophthisis (NPH) is an autosomal-recessive ciliopathy representing one of the most frequent causes of kidney failure in childhood characterized by a broad clinical and genetic heterogeneity. Applied to one of the worldwide largest cohorts of patients with NPH, genetic analysis encompassing targeted and whole exome sequencing identified disease-causing variants in 600 patients from 496 families with a detection rate of 71%. Of 788 pathogenic variants, 40 known ciliopathy genes were identified. However, the majority of patients (53%) bore biallelic pathogenic variants in NPHP1. NPH-causing gene alterations affected all ciliary modules defined by structural and/or functional subdomains. Seventy six percent of these patients had progressed to kidney failure, of which 18% had an infantile form (under five years) and harbored variants affecting the Inversin compartment or intraflagellar transport complex A. Forty eight percent of patients showed a juvenile (5-15 years) and 34% a late-onset disease (over 15 years), the latter mostly carrying variants belonging to the Transition Zone module. Furthermore, while more than 85% of patients with an infantile form presented with extra-kidney manifestations, it only concerned half of juvenile and late onset cases. Eye involvement represented a predominant feature, followed by cerebellar hypoplasia and other brain abnormalities, liver and skeletal defects. The phenotypic variability was in a large part associated with mutation types, genes and corresponding ciliary modules with hypomorphic variants in ciliary genes playing a role in early steps of ciliogenesis associated with juvenile-to-late onset NPH forms. Thus, our data confirm a considerable proportion of late-onset NPH suggesting an underdiagnosis in adult chronic kidney disease.

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Fichiers liés : S0085253823003770.pdf

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