Philippe JEAN-PIERRE

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• Type de publi. : Article dans une revue
• Date de publi. : 20/05/2021
• Auteurs : Nuria KoteckiMaria Alice B FranzoiMarianne PaesmansFlorian ClatotEdith BorcomanAnthony GonçalvesPhilippe BarthelemyClaire CheymolJean-Pierre DelordAndrea GombosVincent VanhaudenardeStephane HolbrechtsFrancois DuhouxJean-Luc Re CanonLore DecosterHannelore DenysCaroline DuhemNadège KindtAhmad Awada
• Organismes : Centre de Recherche en Cancérologie de Marseille
• Publié dans Journal of Clinical Oncology le 01/11/2020

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Résumé : TPS2066 Background: Better knowledge on the evolving epidemiology and biology of CNS metastases are key elements for the development of new treatment strategies and identification of promising therapeutic targets. A multidisciplinary Brain Metastases Clinical Research Platform called BrainStorm was launched by the Jules Bordet Institute and the Oncodistinct network. The BrainStorm program includes mainly patients with non-CNS metastatic solid tumors with high risk of developing CNS metastases allowing to build a large database focusing on three time periods: before the diagnosis of CNS metastases (Part A), at diagnosis (Part B) and after the diagnosis of CNS metastases (Part C). Methods: Subjects with newly diagnosed non-CNS metastases or up to 24 months from diagnosis of non-CNS metastases from triple-negative and HER2-positive breast cancer, lung cancer and melanoma are eligible for part A of the program. Subjects presenting with a 1st CNS event and not yet enrolled (previously mentioned cohorts and a cohort of other tumor types) can enter directly in parts B and subsequently part C of the study. Eligible subjects are followed for 48 months for relevant clinical data, neurological examinations, quality of life, survival status, and undergo examinations and samplings (Table 1). A total of 280 subjects (40 per cohort) with a 1st CNS event will be enrolled. The main objectives of the program are to collect clinical and biological data with the aim to identify risk factors for CNS metastases development (Part A) and to better understand the biology of CNS metastases (brain and leptomeningeal –Parts B and C) aiming to discover new targets for therapy and intensify the multidisciplinary approach for the management of CNS metastases from solid tumors. The translational part of the program will evaluate among others the use of cerebrospinal fluid circulating tumor DNA (CSF-ctDNA) as a surrogate for CNS metastases in order to characterize its molecular landscape. Currently, the study is recruiting in several sites within the Oncodistinct network. The data collected will help to develop innovative multidisciplinary research projects that could be implemented in all parts of the BrainStorm program. Clinical trial information: NCT04109131. [Table: see text]

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• Type de publi. : Communication dans un congrès
• Date de publi. : 20/05/2021
• Auteurs : Jean-Luc MoriceauGéraldine GuérillotPierre-Antoine ChardelPhilippe Castelnau
• Organismes : Département Droit, Économie et Finances Laboratoire en Innovation, Technologies, Economie et Management (EA 7363) Umalis lab (ESCP Europe & Institut Mines-Télécom-Télécom Ecole de Management) Institut interdisciplinaire d'anthropologie du contemporain Laboratoire Sens et Compréhension du Monde Contemporain Département Droit, Économie et Finances Département Droit, Économie et Finances Laboratoire en Innovation, Technologies, Economie et Management (EA 7363)

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• Type de publi. : Article dans une revue
• Date de publi. : 17/05/2021
• Auteurs : Charlotte ArnaudMarion BoulangerAurélien LorthioirLaurence AmarArshid AzarineLouis BoyerGilles ChatellierSilvia Di MonacoXavier JeunemaitreAdrian KastlerElie MousseauxCatherine OppenheimFrédéric ThonyAlexandre PersuJeffrey W OlinAnne BlanchardEmmanuel TouzéAntoine ChedidBéatrice FiquetPierre‐françois PlouinJean‐philippe BaguetOlivier OrmezzanoFrançois SilholEric BodiguelValérie DomigoMarta PasquiniDenis TrystramPierre ClavelouBernard ChamontinBéatrice Duly‐bouhanickHilde HénonClaire Mounier‐vehierParla AstarciPierre GoffetteFrank HammerJean‐philippe LengeléFrancesca SeverinoRobert VerhelstClaire Le HelloPhilippe GosseDominique HervéFernando PicoMichèle KesslerPatrick RossignolYves SansonMathieu ZuberMikaël MazighiSonia Alamowitch
• Organismes : Physiopathologie et imagerie des troubles neurologiques CHU Caen Normandie – Centre Hospitalier Universitaire de Caen Normandie Physiopathologie et imagerie des troubles neurologiques CHU Caen Normandie – Centre Hospitalier Universitaire de Caen Normandie Hôpital Européen Georges Pompidou [APHP] Hôpital Européen Georges Pompidou [APHP] Service de radiologie cardio-vasculaire [CHU HEGP] CHU Gabriel Montpied [Clermont-Ferrand] Hôpital Européen Georges Pompidou [APHP] Department of Medical Sciences [Turin, Italy] Université Catholique de Louvain = Catholic University of Louvain Cliniques Universitaires Saint-Luc [Bruxelles] Hôpital Européen Georges Pompidou [APHP] Centre Hospitalier Universitaire [CHU Grenoble] Service de radiologie cardio-vasculaire [CHU HEGP] Institut de psychiatrie et neurosciences de Paris Service de neuroradiologie [Paris] Centre Hospitalier Universitaire [CHU Grenoble] Université Catholique de Louvain = Catholic University of Louvain Cliniques Universitaires Saint-Luc [Bruxelles] Icahn School of Medicine at Mount Sinai [New York] CIC - HEGP Physiopathologie et imagerie des troubles neurologiques CHU Caen Normandie – Centre Hospitalier Universitaire de Caen Normandie Défaillance Cardiovasculaire Aiguë et Chronique Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] French-Clinical Research Infrastructure Network - F-CRIN [Paris]
• Publié dans Journal of the American Heart Association le 28/10/2020

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Résumé : Background Cervical artery dissection (CeAD) is a frequent manifestation of fibromuscular dysplasia (FMD). However, risk factors for CeAD are unknown. We investigated factors associated with CeAD in the ARCADIA (Assessment of Renal and Cervical Artery Dysplasia) registry. Methods and Results The ARCADIA registry includes women or men aged ≥18 years, with a diagnosis of renal, cervical, or intracranial artery FMD, who were prospectively recruited at 16 university hospitals in France and Belgium. Diagnosis of acute or past CeAD at inclusion was established on imaging according to standard diagnostic criteria. Associations between potential determinants and CeAD were assessed by logistic regression analyses. Among 469 patients (75 men) with FMD, 65 (13.9%) had CeAD. Patients with CeAD were younger, more likely to be men, have a history of migraine, and less likely to have a history of hypertension than patients without CeAD. In the multivariable analysis, male sex (odds ratio [OR], 2.66; 95% CI, 1.34–5.25), history of migraine (OR, 1.90; 95% CI, 1.06–3.39), age ≥50 years (OR, 0.41; 95% CI, 0.23–0.73), history of hypertension (OR, 0.35; 95% CI, 0.20–0.64), and involvement of ≥3 vascular beds (OR, 2.49; 95% CI, 1.15–5.40) were significantly associated with CeAD. To validate the association between CeAD and sex, we performed a systematic review. We collected additional data on sex from 2 published studies and unpublished data from the US Registry for Fibromuscular Dysplasia and the European/International FMD Registry. In the pooled analysis (289 CeAD, 1933 patients), male sex was significantly associated with CeAD (OR, 2.04; 95% CI, 1.41–2.95; I 2 =0%). Conclusions In patients with FMD, male sex and multisite involvement are associated with CeAD, in addition to other previously known risk factors.

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Fichiers liés : JAHA.120.018311.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 11/05/2021
• Auteurs : Jean ReignierAmélie Le GougeJean-Baptiste LascarrouDjillali AnnaneLaurent ArgaudYannick HourmantPierre AsfarJulio BadieMai-Anh NayNicolae-Vlad BotocLaurent BrisardHoang-Nam BuiDelphine ChatellierLouis ChauvelotAlain CombesChristophe CraccoMichaël DarmonVincent DasMatthieu DebarreAgathe DelboveJérôme DevaquetSebastian VoicuNadia Aissaoui-BalanantLouis-Marie DumontJohanna OzielOlivier GontierSamuel GroyerBertrand GuidetSamir JaberFabien LambiotteChristophe LeroyPhilippe LetocartBenjamin MadeuxJulien MaizelOlivier MartinetFrédéric MartinoEmmanuelle MercierJean-Paul MiraSaad NseirWalter PicardGaël PitonGaetan PlantefeveJean-Pierre QuenotAnne RenaultLaurent GuérinJack RichecoeurJean-Philippe RigaudFrancis SchneiderDaniel SilvaMichel SirodotBertrand SouweineFlorian ReizineFabienne TamionNicolas TerziDidier ThéveninGuillaume ThieryNathalie Thieulot-RolinJean-François TimsitFrançois TinturierPatrice TirotThierry VanderlindenIsabelle VinatierChristophe VinsonneauDiane MaugarsBruno Giraudeau
• Organismes : Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre d’Investigation Clinique [Tours] CIC 1415 Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Service médical des soins intensifs [CHU Raymond Poincaré] Cardiovasculaire, métabolisme, diabétologie et nutrition Hôpital Edouard Herriot [CHU - HCL] Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Hospitalier Universitaire d'Angers Hôpital Nord Franche-Comté [Hôpital de Trévenans] Centre Hospitalier Regional d'Orléans CH de Saint-Malo [Broussais] Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Service Anesthésie - Réanimation [Bordeaux] Centre hospitalier universitaire de Poitiers = Poitiers University Hospital Service d'anesthésie-réanimation [Centre Hospitalier Lyon Sud - HCL] Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases Centre Hospitalier d'Angoulême Service d'anesthésie-réanimation-CTB [CHU Saint Louis] Centre Hospitalier Intercommunal André Grégoire [Montreuil] Hôpital de Saint-Brieuc [Hôpital Yves Le Foll] Centre hospitalier Bretagne Atlantique (Morbihan) Hôpital Foch [Suresnes] Département d’Anesthésie-Réanimation-SMUR [Hôpital Lariboisière] Service d'Anesthésie-Réanimation [CHU HEGP] Service de Réanimation Médico-Chirurgicale [Hôpital Louis Mourier] Service d'anesthésie-réanimation [Avicenne] Service de Réanimation polyvalente [Chartres] Centre hospitalier de Montauban CHU Saint-Antoine [AP-HP] Centre Hospitalier Régional Universitaire [Montpellier] Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] Centre Hospitalier de Valenciennes Centre Hospitalier Emile Roux [Le Puy-en-Velay] Centre Hospitalier Rodez Centre Hospitalier de Bigorre [Tarbes] Médecine Intensive-Réanimation [CHU Amiens] Mécanismes physiopathologiques et conséquences des calcifications cardiovasculaires - UR UPJV 7517 Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion] CHU Pointe-à-Pitre / Abymes [Guadeloupe] Centre Hospitalier Régional Universitaire de Tours Service de réanimation médicale polyvalente [CHU Cochin] Centre Hospitalier Régional Universitaire [CHU Lille] Centre hospitalier de Pau Service de Réanimation médicale [CHRU Besançon] Centre hospitalier Victor Dupouy [Centre hospitalier d'Argenteuil] Service de Réanimation Médicale (CHU de Dijon) CHRU Brest - Service de Réanimation Médicale Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre] Centre Hospitalier Simone Veil de Beauvais [Beauvais] Service de réanimation polyvalente [Centre Hospitalier de Dieppe] Service de Médecine Intensive et Réanimation [Strasbourg] Centre Hospitalier de Saint-Denis [Ile-de-France] Centre Hospitalier d'Annecy Genevois Service Anésthésie et Réanimation [CHU Clermont-Ferrand] Service d'Anesthésie Réanimation [Rennes] Service de Réanimation Médicale [CHU Rouen] Service de Réanimation Médicale [Grenoble] Centre Hospitalier de Lens Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] Centre Hospitalier de Melun Service d'anesthésie - réanimation chirurgicale [CHU Bichat] Médecine Intensive-Réanimation [CHU Amiens] Service Réanimation médico-chirurgicale [CH Le Mans] Groupement des Hôpitaux de l'Institut Catholique de Lille Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon Centre Hospitalier de Béthune Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre d’Investigation Clinique [Tours] CIC 1415
• Publié dans BMJ Open le 26/10/2020

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Résumé : Introduction: International guidelines include early nutritional support (≤48 hour after admission), 20–25 kcal/kg/day, and 1.2–2 g/kg/day protein at the acute phase of critical illness. Recent data challenge the appropriateness of providing standard amounts of calories and protein during acute critical illness. Restricting calorie and protein intakes seemed beneficial, suggesting a role for metabolic pathways such as autophagy, a potential key mechanism in safeguarding cellular integrity, notably in the muscle, during critical illness. However, the optimal calorie and protein supply at the acute phase of severe critical illness remains unknown. NUTRIREA-3 will be the first trial to compare standard calorie and protein feeding complying with guidelines to low-calorie low-protein feeding. We hypothesised that nutritional support with calorie and protein restriction during acute critical illness decreased day 90 mortality and/or dependency on intensive care unit (ICU) management in mechanically ventilated patients receiving vasoactive amine therapy for shock, compared with standard calorie and protein targets. Methods and analysis: NUTRIREA-3 is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients receiving invasive mechanical ventilation and vasoactive amine therapy for shock and given early nutritional support according to one of two strategies: early calorie-protein restriction (6 kcal/kg/day-0.2–0.4 g/kg/day) or standard calorie-protein targets (25 kcal/kg/day, 1.0–1.3 g/kg/day) at the acute phase defined as the first 7 days in the ICU. We will include 3044 patients in 61 French ICUs. Two primary end-points will be evaluated: day 90 mortality and time to ICU discharge readiness. The trial will be considered positive if significant between-group differences are found for one or both alternative primary endpoints. Secondary outcomes include hospital-acquired infections and nutritional, clinical and functional outcomes. Ethics and dissemination: The NUTRIREA-3 study has been approved by the appropriate ethics committee. Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals.

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Fichiers liés : e045041.full.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 10/05/2021
• Auteurs : Chakali EswaraiahDi LiRay FuruyaTetsuo HasegawaDaniel R. van RossumKeping QiuNagayoshi OhashiKate PattleSarah SadavoyCharles HullDavid BerryYasuo DoiTao-Chung ChingShih-Ping LaiJia-Wei WangPatrick M KochJungmi KwonWoojin KwonPierre BastienDoris ArzoumanianSimon CoudéArchana SoamLapo FanciulloHsi-Wei YenJunhao LiuThiem HoangWen Ping ChenYoshito ShimajiriTie LiuZhiwei ChenHua-Bai LiA-Ran LyoJihye HwangDoug JohnstoneRamprasad RaoNguyen Bich NgocPham Ngoc DiepSteve MairsHarriet ParsonsMotohide TamuraMehrnoosh TahaniHuei-Ru Vivien ChenFumitaka NakamuraHiroko ShinnagaYa-Wen TangJungyeon ChoChang Won LeeShu-Ichiro InutsukaTsuyoshi InoueKazunari IwasakiLei QianJinjin XieDalei LiHong-Li LiuChuan-Peng ZhangMike ChenGuoyin ZhangLei ZhuJianjun ZhouPh. AndréSheng-Yuan LiuJinghua YuanXing LuNicolas PerettoTyler BourkeDo-Young ByunSophia DaiYan DuanHao-Yuan DuanDavid EdenBrenda MatthewsJason FiegeLaura FisselKee-Tae KimChin-Fei LeeJongsoo KimTae-Soo PyoYunhee ChoiMinho ChoiAntonio ChrysostomouEun Jung ChungLe Ngoc TramErica FranzmannPer FribergRachel FriesenGary FullerTim GledhillSarah GravesJane GreavesMatt GriffinQilao GuIlseung HanJennifer HatchellSaeko HayashiMartin HoudeKoji KawabataIl-Gyo JeongJi-Hyun KangSung-Ju KangMiju KangAkimasa KataokaFrancisca KemperMark RawlingsJonathan RawlingsBrendan RetterJohn RicherAndrew RigbyHiro SaitoGiorgio SaviniAnna ScaifeMasumichi SetaGwanjeong KimKyoung Hee KimMi-Ryang KimFlorian KirchschlagerJason KirkMasato KobayashiVera KonyvesTakayoshi KusuneKevin LacailleChi-Yan LawSang-Sung LeeYong-Hee LeeMasafumi MatsumuraGerald Moriarty-SchievenTetsuya NagataHiroyuki NakanishiTakashi OnakaGeumsook ParkXindi TangKohji TomisakaYusuke TsukamotoSerena VitiHongchi WangAnthony WhitworthHyunju YooHyeong-Sik YunTetsuya ZenkoYapeng ZhangIlse de LoozeC. Darren DowellStewart EyresSam FalleJean-François RobitailleSven van Loo
• Organismes : Laboratoire d'Astrophysique de Marseille Institut de Planétologie et d'Astrophysique de Grenoble
• Publié dans The Astrophysical Journal Letters le 28/10/2020

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Résumé : Abstract We have obtained sensitive dust continuum polarization observations at 850 μ m in the B213 region of Taurus using POL-2 on SCUBA-2 at the James Clerk Maxwell Telescope as part of the B -fields in STar-forming Region Observations (BISTRO) survey. These observations allow us to probe magnetic field ( B -field) at high spatial resolution (∼2000 au or ∼0.01 pc at 140 pc) in two protostellar cores (K04166 and K04169) and one prestellar core (Miz-8b) that lie within the B213 filament. Using the Davis–Chandrasekhar–Fermi method, we estimate the B -field strengths in K04166, K04169, and Miz-8b to be 38 ± 14, 44 ± 16, and 12 ± 5 μ G, respectively. These cores show distinct mean B -field orientations. The B -field in K04166 is well ordered and aligned parallel to the orientations of the core minor axis, outflows, core rotation axis, and large-scale uniform B -field, in accordance with magnetically regulated star formation via ambipolar diffusion taking place in K04166. The B -field in K04169 is found to be ordered but oriented nearly perpendicular to the core minor axis and large-scale B -field and not well correlated with other axes. In contrast, Miz-8b exhibits a disordered B -field that shows no preferred alignment with the core minor axis or large-scale field. We found that only one core, K04166, retains a memory of the large-scale uniform B -field. The other two cores, K04169 and Miz-8b, are decoupled from the large-scale field. Such a complex B -field configuration could be caused by gas inflow onto the filament, even in the presence of a substantial magnetic flux.

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Fichiers liés : Eswaraiah_2021_ApJL_912_L27.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 06/05/2021
• Auteurs : Geoffroy PouletFanny GarlanSonia GarrigouEleonora ZontaLeonor BenhaimMarie-Jennifer CarrillonAudrey DidelotDelphine Le CorreClaire MulotPhilippe NizardFrederic GinotAudrey Boutonnet-RodatHelene BlonsJean-Baptiste BachetJulien TaïebAziz ZaananVanna GeromelLaurence PellegrinaPierre Laurent-PuigShu-Fang Wang-RenaultValerie Taly
• Organismes : Centre de Recherche des Cordeliers Centre de Recherche des Cordeliers Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique Centre de Recherche des Cordeliers Centre de Recherche des Cordeliers Institut Gustave Roussy Centre de Recherche des Cordeliers Département de chirurgie viscérale [Gustave Roussy] Centre de Recherche des Cordeliers Centre de Recherche des Cordeliers Centre de Recherche des Cordeliers Centre de Recherche des Cordeliers Hôpital Européen Georges Pompidou [APHP] Centre de Recherche des Cordeliers Adelis Technologies Adelis Technologies Centre de Recherche des Cordeliers Service d'oncologie médicale [CHU HEGP] Centre de Recherche des Cordeliers CHU Pitié-Salpêtrière [AP-HP] Centre de Recherche des Cordeliers Service d'oncologie médicale [CHU HEGP] Centre de Recherche des Cordeliers Service d'oncologie médicale [CHU HEGP] Eurofins Biomnis Eurofins Biomnis Centre de Recherche des Cordeliers Service d'oncologie médicale [CHU HEGP] Centre de Recherche des Cordeliers Centre de Recherche des Cordeliers
• Publié dans Frontiers in Oncology le 26/10/2020

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Résumé : Background: Cellular-cell free-DNA (ccfDNA) is being explored as a diagnostic and prognostic tool for various diseases including cancer. Beyond the evaluation of the ccfDNA mutational status, its fragmentation has been investigated as a potential cancer biomarker in several studies. However, probably due to a lack of standardized procedures dedicated to preanalytical and analytical processing of plasma samples, contradictory results have been published. Methods: ddPCR assays allowing the detection of KRAS wild-type and mutated sequences ( KRAS p.G12V, pG12D, and pG13D) were designed to target different fragments sizes. Once validated on fragmented and non-fragmented DNA extracted from cancer cell lines, these assays were used to investigate the influence of the extraction methods on the non-mutated and mutated ccfDNA integrity reflected by the DNA integrity index (DII). The DII was then analyzed in two prospective cohorts of metastatic colorectal cancer patients (RASANC study n = 34; PLACOL study n = 12) and healthy subjects ( n = 49). Results and Discussion: Our results demonstrate that ccfDNA is highly fragmented in mCRC patients compared with healthy individuals. These results strongly suggest that the characterization of ccfDNA integrity hold great promise toward the development of a universal biomarker for the follow-up of mCRC patients. Furthermore, they support the importance of standardization of sample handling and processing in such analysis.

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Fichiers liés : fonc-11-639675.pdf

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• Type de publi. : Communication dans un congrès
• Date de publi. : 04/05/2021
• Auteurs : Antonin TomassoCéline Bressy-LeandriDidier BinderVincent DelvignePaul FernandesChristophe TufféryPierre AllardThierry AubryAlain BeechingVincent BlouetChristophe BorgnonFrançoise BostynJacques Léopold BrochierJean-Philippe CollinVéronique BrunetGuilhem ConstansSylvie Coutard
• Organismes : Culture et Environnements, Préhistoire, Antiquité, Moyen-Age Centre National de la Recherche Scientifique Service régional de l'archéologie, Ajaccio Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés Culture et Environnements, Préhistoire, Antiquité, Moyen-Age Centre National de la Recherche Scientifique Centre National de la Recherche Scientifique Technologie et Ethnologie des Mondes Préhistoriques SARL Paleotime, 38250 Villard-de-Lans Technologie et Ethnologie des Mondes Préhistoriques Technologie et Ethnologie des Mondes Préhistoriques Institut national de recherches archéologiques préventives Centre National de la Recherche Scientifique Technologie et Ethnologie des Mondes Préhistoriques ARCHEORIENT - Environnements et sociétés de l'Orient ancien Service régional de l'archéologie du Grand Est, site de Metz Institut national de recherches archéologiques préventives Trajectoires - UMR 8215 Université Paris 1 Panthéon-Sorbonne - UFR Histoire de l'art et archéologie Centre National de la Recherche Scientifique Laboratoire méditerranéen de préhistoire Europe-Afrique Centre de recherches en archéologie et patrimoine Trajectoires - UMR 8215 Institut national de recherches archéologiques préventives Trajectoires - UMR 8215 Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés Institut national de recherches archéologiques préventives Laboratoire de géographie physique : Environnements Quaternaires et Actuels

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Résumé : L’élaboration des lithothèques constitue l’un des piliers de la recherche sur la caractérisation et la provenance des roches siliceuses taillées durant la Préhistoire. Depuis plus de 40 ans, dans de multiples régions, des prospections sont menées pour documenter et échantillonner les gîtes de matériaux siliceux qui sont autant de sources potentielles d'approvisionnement des groupes préhistoriques. Ces référentiels, hétérogènes, ont été construits de manières diverses et la recherche demeure à ce jour fortement cloisonnée. Or, la connaissance des potentialités siliceuses à grande échelle est essentielle pour mettre en évidence des circulations à longue distance, de nature à modifier notre perception des territoires durant la Préhistoire. À partir d’une enquête nationale sur les lithothèques, a été initiée une démarche de mise en réseau des acteurs portée par le Groupe de recherche Silex. Elle vise à pérenniser les données (base de données) ainsi qu’à partager et harmoniser les pratiques pour redéfinir le périmètre scientifique des lithothèques. Périmètre qui évolue en fonction des méthodologies appliquées et des problématiques actuelles de la recherche préhistorique.

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• Type de publi. : Article dans une revue
• Date de publi. : 03/05/2021
• Auteurs : Anne MontfortFlorie BertrandJulia RochotteJulia GilhodesThomas FilleronJean MilhèsCarine DufauCaroline ImbertJoelle RiondMarie TosoliniChristopher ClarkeFlorent DufourAndrei ConstantinescuNilton de França JuniorVirginie GarciaMichel RecordPierre CordelierPierre BroussetPhilippe RochaixSandrine Silvente-PoirotNicole ThervilleNathalie Andrieu-AbadieThierry LevadeYusuf HannunHervé BenoistNicolas MeyerOlivier MicheauCéline ColaciosBruno Ségui
• Organismes : Centre de Recherches en Cancérologie de Toulouse Centre de Recherches en Cancérologie de Toulouse Centre de Recherches en Cancérologie de Toulouse Institut Universitaire du Cancer de Toulouse - Oncopole Institut Universitaire du Cancer de Toulouse - Oncopole Centre de Recherches en Cancérologie de Toulouse Centre de Recherches en Cancérologie de Toulouse Centre de Recherches en Cancérologie de Toulouse Centre de Recherches en Cancérologie de Toulouse Centre de Recherches en Cancérologie de Toulouse Stony Brook University [SUNY] Lipides - Nutrition - Cancer [Dijon - U1231] Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer Lipides - Nutrition - Cancer [Dijon - U1231] Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer Lipides - Nutrition - Cancer [Dijon - U1231] Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer Centre de Recherches en Cancérologie de Toulouse Centre de Recherches en Cancérologie de Toulouse Institut Universitaire du Cancer de Toulouse - Oncopole Centre de Recherches en Cancérologie de Toulouse Centre de Recherches en Cancérologie de Toulouse Institut Universitaire du Cancer de Toulouse - Oncopole Centre de Recherches en Cancérologie de Toulouse Institut Universitaire du Cancer de Toulouse - Oncopole Centre de Recherches en Cancérologie de Toulouse Institut Universitaire du Cancer de Toulouse - Oncopole Centre de Recherches en Cancérologie de Toulouse Centre de Recherches en Cancérologie de Toulouse Centre de Recherches en Cancérologie de Toulouse Institut Fédératif de Biologie (IFB) Stony Brook University [SUNY] Centre de Recherches en Cancérologie de Toulouse Centre de Recherches en Cancérologie de Toulouse Institut Universitaire du Cancer de Toulouse - Oncopole Lipides - Nutrition - Cancer [Dijon - U1231] Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer Centre de Recherches en Cancérologie de Toulouse Centre de Recherches en Cancérologie de Toulouse
• Publié dans Cancer Immunology Research le 20/04/2021

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Résumé : Dysregulation of lipid metabolism affects the behavior of cancer cells, but how this happens is not completely understood. Neutral sphingomyelinase 2 (nSMase2), encoded by SMPD3, catalyzes the breakdown of sphingomyelin to produce the anti-oncometabolite ceramide. We found that this enzyme was often downregulated in human metastatic melanoma, likely contributing to immune escape. Overexpression of nSMase2 in mouse melanoma reduced tumor growth in syngeneic wild-type but not CD8-deficient mice. In wild-type mice, nSMase2-overexpressing tumors showed accumulation of both ceramide and CD8+ tumor-infiltrating lymphocytes, and this was associated with increased level of transcripts encoding IFNγ and CXCL9. Overexpressing the catalytically inactive nSMase2 failed to alter tumor growth, indicating that the deleterious effect nSMase2 has on melanoma growth depends on its enzymatic activity. In vitro, small extracellular vesicles from melanoma cells overexpressing wild-type nSMase2 augmented the expression of IL12, CXCL9, and CCL19 by bone marrow-derived dendritic cells, suggesting that melanoma nSMase2 triggers T helper 1 (Th1) polarization in the earliest stages of the immune response. Most importantly, overexpression of wild-type nSMase2 increased anti-PD-1 efficacy in murine models of melanoma and breast cancer, and this was associated with an enhanced Th1 response. Therefore, increasing SMPD3 expression in melanoma may serve as an original therapeutic strategy to potentiate Th1 polarization and CD8+ T-cell-dependent immune responses and overcome resistance to anti-PD-1.

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Fichiers liés : 568.full.pdf

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• Type de publi. : Rapport
• Date de publi. : 03/05/2021
• Auteurs : Marion FouchardJean-Pierre HébrardPhilippe Ponel
• Organismes : Ligue pour la protection des oiseaux PACA Institut méditerranéen de biodiversité et d'écologie marine et continentale Institut méditerranéen de biodiversité et d'écologie marine et continentale

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Fichiers liés : Fouchard et al Rapport 2021.pdf

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Source

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• Type de publi. : Article dans une revue
• Date de publi. : 01/05/2021
• Auteurs : Mark McclanahanMichael DempseyHelen ColhounIsabelle ZobouyanPatrick PicaultAurelie PerthuisChristine MorrelloDominique Fournie-LloretZhu ChengyueRaluca CotrutaMarion VincendetMarc SottyMaxime MourguesLamia MetwallyBenjamin HalleHelene Dubois-GachePauline BarraudPascale BeltranAntony AdamoChristelle RondelAnne OurliacMickael NormandVirginie LoizeauValerie GouetAlexis EtienneChristelle LorenzatoJérôme RepincayChristelle BerthouAnthony CoulangeRaphael BejuitMichel ScemamaKatarina KralovaMaud LamoureuxNafissa BengraitFadela BenbernouValerie PellanSebastien SopenaJennifer ShellerLucile SmithBetim OkanBicky MthombeniAsmaa MrabtiUlises MoralesMyriam MonierJulien LabeirieCarine JavierreGayatri JaiwalMegan HeathJan HealySeverine GuillouCaroline GobillotCecile GacheSzilvia DomokosDawn DevaulJoseph CianciaruloMaddy BrocklehurstImane BriguiCecile BouancheauMhamed BekkoucheEmmy BadreddineDorthe AndersenVeronique AgnettiMelanie VerrierJudith MurphySylvie FontecaveDouglas FaustinoNathalie BougonMarie-France BrégeaultShahidul IslamLena GrunbergMichelle ShawLiddy GriffithJulie ButtersAnne LuytenCaroline AlsweilerTabassome SimonElodie DrouetMadeleine BezaultCarla RovitoAndrea PascualMelissa WestbrookTyrus RorickKirby QuinteroAnita HepditchLisa BerdanJanine ValirisCaroline RatkyAlexander MatthewsJulianna WozniakJanaina OliveiraAnelise KawakamiFlavia EgydioEric BallDavid LaxsonJohn HunterJohn KostisKishor VoraRamprasad DandillayaGeraldine GardnerBill HarrisDouglas JacobyJay AndersonRichard GilmoreRobert FosterJames WelkerTerry WellsJoanne CoblerJustine KrawczykLaura AkrightDawood GamilHoward RubensteinGregory GieslerMichael LovePurushotham KothaGary ConradNizar AssiTammam Al JoundiAref RahmanJohn Paul GibsonAlexander MacdonellDouglas DenhamImran DotaniStuart ChristensonJohn SchmedtjeCharles EatonGopal ChalavaryaJohn GilbertBranislav SchifferdeckerJohn HenrySherrill MurphyMark ChangWilliam PennyJessica BirchemHimanshu AgarwalSandeep KhuranaDonald WesterhausenWilliam KeenHenry LuiSuhail DohadRonald KarlsbergCarlos BayronMark ZaineaDiwakar JainP. Sandy SundramMichael SchwartzSamir TurkMartin McgoughJoel LandzbergSteven EisenbergDwight StapletonDaniel SpornMichael RadinEric YangRobert BarruccoRobert FishbergMichael BerlowitzHinan AhmedRiyaz BashirMukesh SharmaRakesh VohraPaul NagerTheodore PopeAhed NahhasF. Martin LesterKapildeo LotunNampalli VijayJason HallMajed ChaneAnthony VoSuneet MittalJanet StrainDouglas SpriggsSeals AlbertEdward PereiraSteven SchwartzMark NeustelLawrence GimpleDouglas GuySteve DiamantisWilliam FrenchStewart PollockMichael FarrarNorman ErenrichMichael RaySamir PancholyDonald EagertonEugene SorokaStuart FischerDavid HoffmanStephen WelkaJoshua PurowSteven LupovitchGreg KumkumianAjit KhairaAmit KheraParag JoshiPeter RossiMartin BerkRohr KathrynRobert WeissEdmund ClaxtonH. John MaraisKwan LeeAjay LabrooAyim Akyea-DjamsonRonald BlonderJames StraderRavi BhagwatNeal PerlmutterMark XenakisDaniel FisherSridhar BanuruNaseem JaffraniDinesh SingalPhilip O’donnellKeattiyoat WattanakitClara MasseyGeert JongChristopher MalozziAndreas WaliMohamadali AmlaniAndrey EspinozaGlen TonnessenMalcolm FosterKevin SilverJeffrey KuvinCarey KimmelstielPhillip RozemanArthur LoussararianFred ChaleffDennis FriedmanThomas KnutsonMladen VidovichHyeun (tom) ParkLiwa YounisJaime GerberCharles CareyMarilyn KingGeorge VetrovecAntonio AbbateAjit RaisinghaniCharles LambertJames FairlambGregory RoseJoseph RossiZachary HodesEbrahimi RaminFreny ModyAlan ChuThomas GalskiDaniels ChristopherWade MayAlvaro AlonsoAnand IrimpenHoward WeintraubMahfouz El ShahawyNorman LeporParilak LeonardEichenlaub TimothyRosemary NowinsJason LindseyKeith FriedmanWilliam HerzogRobert PedersonMark PiconeCarsten SchmalfussMasoud AzizadWilliam SheldonThomas BlokStephen VoyceVipul PanchalJoseph McgarveyZubair JafarGeorge PonceFiras ZahrPhillip HorwitzNizar DaboulRolf AndersenShawn SpeirsJack WhitakerSharan MahalGeoffrey KlineNaim FarhatTimothy SchuchardDavid HendersonChristian GringBabak VakiliNandkishore RanadiveSumeet SubherwalOthman IslamMatthew WhiteJalal AbbasStephen ThewWenwu ZhangBrent MclaurinPeter KuhlmanEdward TeufelJohn LarryArnold GhitisGeorge KinzfoglAnna BortnickChad LinkRose DoBrack HattlerAnil KumarMark IzzoRahul AggarwalVipul ShahMazen Abu-FadelTheodore TakataWinfried WaiderHoward LeviteSanjay ShettyNicholas KondoFriederike KeatingKerensky RichardChristopher DanielsJoseph GelorminiBrett BermanCarl PepineDenise JanosikAnil ShahNarendra SinghSarah FentonJames RiderWayne LeimbachAmarnath VedereMaitreya ThakkarJohn PasquiniShahram YazdaniWilliam DavisJohn KobayashiAndrew SumnerJoseph MoranMatthew JanikJames BengstonTauqir GorayaGeorge DoddsHarish ChandnaMichael KorenSai DevarapalliVinay MalhotraKim KlanckeIon JovinAngel MulkaySunder RaoAmir MalikTariq HaddadKenneth SabatinoDaniel DotyLuther CarterSteven CohenBarry HarrisKatie MoriartyWilliam NelsonFadi El-AhdabMichael d'UrsoEric CarlsonFaiq AkhterMouhamad AbdallahImran ArifDavid SuhThomas AmidonEve GillespieThomas HaldisThomas KnickelbineLindsey WhiteMian HasanPerry KrichmarCara EastPriya KumarIra LieberPatrick CambierGeorges DagherMohammad ShoukfehMisal KhanJonathan WaltmanLes ForgoshEdward KosinskiWilliam RogersMichael RosenbergShi-Chi ChengScott WrightEnrique FloresCarlos InceAnn Elizabeth MohartSanjeev PuriAbul KhanAlan WisemanBruce PalmerCharles DahlCharles Treasure IiDavid BrabhamDuccio BaldariGil VardiNicholas Ossei-GerningSean GallagherJulian HalcoxDavid FitzmauricePeter WilkinsonRob ButlerDavid SprigingsDavid SharmanTimothy ReynoldsAyyaz SultanGohar RahmanTelal MudawiSimon ThackrayRichard OliverMuhammad CheemaMohammad AyazAdrian BrodisonAnthony MathurHandrean SoranAudrius SimaitisRobert GerberHoner KadrCraig BarrTerry LevyJohn KurianSimon SmithRangasamy MuthusamySam McclureHuw GriffithsRobert StoreyDavid SarkarDenise BraganzaEduardas SubkovasSyed M.R. IqbalYuk-Ki WongPiers CliffordRajesh AggarwalAndrew MoriartyKaeng LeeAzfar ZamanJasper TrevelyanVolodymyr ZheleznyyAnatolii RudenkoBorys GoloborodkoGeorgiy DzyakOlexiy UshakovOlga BarnaAndriy BagriyMykola VatutinAndriy YagenskyMykola KopytsyaMykola RishkoOleh LeshchukViktor TashchukEkaterina AmosovaOles KutniyAndriy KlantsaYaroslav MalynovskyYuriy KarpenkoYulian KyiakMykola StanislavchukYuriy MostovoyVira TseluykoMykola KushnirIhor KovalskyiLeonid RudenkoValeriy BatushkinDmytro ReshotkoHalyna MyshanychIhor VakaluykAlexander ProkhorovOleksandr KarpenkoLale KoldasErtan UralCevat KirmaMustafa DemirtasMurat ErsanliBulent MutluHakan KultursayAhmet CamsariPaiboon ChotnoparatpatDilok PiyayotaiWirash KehasukcharoenNakarin SansanayudhKrisada SastravahaNattawut WongpraparutApichard SukonthasarnWoravut JintapakornWasant SoonfuangPinij KaewsuwannaChih-Yuan FangTsuei-Yuan HuangJen-Yuan KuoWei Hsiang LinMing-Jer HsiehI-Chang HsiehWei-Hsian YinJuey-Jen HwangMing-En LiuWen-Ter LaiKwo-Chang UengWei-Chuan TsaiOliver GämperliRonald BindeFrancois MachChristian MüllerTiziano MoccettiTorbjörn SundelinUlf AhremarkIngemar TorstenssonSteen Agergaard JensenStefano RomeoOle HansenPeter NicolGeorgios MourtzinisNils WittOla VedinGundars RasmanisStefan BerglundNaomali AmarasenaJagath HerathAjantha RajapakshaThilak SirisenaGnanamoorthy MayurathanVajira SenaratneSepalika MendisRuvan EkanayakaGotabhaya RanasingheSantharaj WijeyasingamJayanthimala JayawardenaKaputella FernandoNimali FernandoChandrike PonnamperumaStanley AmarasekeraNirmali TisseraRuvaiz HaniffaGodwin ConstantinePedro ValdivielsoNorberto Alonso OrcajoAntonio Coca PayerasJuan EscudierJavier Balaguer RecenaPablo Loma-Osorio RinconCésar Morís de La TassaIgnacio Plaza PerezMercedes Camprubí PotauCarlos Gonzalez-JuanateyAmparo BenedictoGabriel Gusi TragantJavier Botas RodriguezJuan Cosín SalesJosé Alberto García LledóJose Francisco Díaz FernándezJosé Antonio Vázquez de PradaJosé de Berrazueta FernándezJose Maria Serrano AntolinJoaquin Alonso MartinJordi Bruguera CortadaManuel de Mora MartinJose Luis ZamoranoLaia Matas PericasFernando Civeira MurilloJavier Fernandez PortalesJose Gonzalez-JuanateyJosé Tuñón FernándezAndres IñiguezDavid Garcia-DoradoFernando Worner DizPablo ToledoBlas Gil-ExtremeraRafael Jesus Hidalgo UrbanoJose Cruz FernándezFrancisco MarínFrancisco Fuentes JimenezVicente Bodí PerisAngel Cequier FillatManuel VidaRajendran MoodleyHelmuth ReuterJoseph MynhardtMahomed SarvanIftikhar EbrahimGarda RiazSoraya CassimjeePatrick CommerfordJan SaaimanThayabran PillayPeter SebastianLouis van ZylDina van AswegenHanlie LotteringMatthys de V. BassonIlse KappHendrik Du Toit TheronEllen Makoali MakotokoJunaid BayatClive CorbettNaresh RanjithHenry CysterMatija CevcNataša Černič ŠuligojJanez PoklukarIvan ŽuranPeter OlexaAndrej DukatRudolf SmikJaroslava StrbovaGabriel KamenskyJuraj SeleckyViliam BuganJozef GonsorcikFrantišek FazekasAndrej DzupinaIvan MajercákJuraj MazurJuraj PalkaMarian HranaiPeter FulopDaniel PellaJan NociarKarol MickoJustin Tang I-ShingHean Yee OngKian-Keong PohTamara JakimovSinisa DimkovicSlobodan DodicAna KaradzicPetar SeferovicDragan DincicJovan BalinovacBranislava TodicSlavica RadovanovicAleksandra ArandjelovicAleksandar StankovicBiljana Putnikovic TosicStevan IlicSvetlana ApostolovicStevo StojicMilika AsaninNebojsa TasicGoran DavidovicNikola IvanovicDragan SimicSergey KanorskyMasterov IlyaIgor IvanovVadim TyrenkoLiudmila EgorovaAnton PovzunYuriy KarpovElena KosmachovaZaur ShogenovElena BaranovaLiudmila GaponKonstantin NikolaevOlga MolchanovaTatiana SotnikovaOlga ReshetkoNiiaz KhasanovIvan GordeevSergey YakushinSergey ShustovEvgeny BaranovTatyana TretyakovaMikhail VoevodaIgor LibovGalina ChumakovaEvgenia AkatovaVladimir ShchekotovNatalya OsokinaInna ViktorovaPetr ChizhovLarisa KhaishevaSergey ShalaevTatiana KhlevchukIgor BokarevNikita LomakinRaisa StryukVictor GurevichAlexander VishnevskyKonstantin ZrazhevskyAlexander GordienkoNadezhda LyaminaValentin MarkovOlga BarbarashZhanna KobalavaOlga OrlikovaYury ShvartsDoina DimulescuRodica Stanescu-CioranuIoan ComanMihaela MalisTom AlexandruAdrian MateiIrinel ParepaDoina RosuConstantin MilitaruCristina BengusMircea C.A. 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ReisWeimar K.S.B. SouzaFernando CostaJuliana de SouzaLuiz Eduardo F. RittGilson FeitosaJose Marin-NetoWladmir SaporitoJose SilveiraPedro SilvaJose Moura JorgeDalton PrecomaEuler Roberto Fernandes ManentiSergio KaiserRoberto BotelhoPaulo LeaesMaria VidottiFreddy EliaschewitzYorghos MichalarosLuiz BodaneseFernando NeuenschwanderMayler O.N. de SantosAna Priscila SoggiaPedro Pimentel FilhoJosé Antonio M. AbrantesAdrian KormannRenato KalilNorberto DudaMaria José A.G. CerqueiraPaulo R.F. RossiRafael RechLilia Nigro MaiaRicardo SilvaFlavio GiorgetoJose NicolauLuciano SousaGilmar ReisBoris GoronjaAdis MuslibegovicDusko VulicAzra Durak-NalbanticMehmed KulićEmir FazlibegovicBelma PojskicZlatko MidzicFahir BarakovicIbrahim TerzicFrank CoolsMarc ClaeysEmanuele BarbatoJohn RoosenCarl ConvensHarry StriekwoldGeert VervoortChristophe BeauloyeKarl DujardinMarc CastadotBart WollaertLuc de WolfMathias C.M. VrolixEtienne HofferAttilio LeoneBruno PirenneKurt HermansDirk FaesFranz WeidingerBernhard FreyGeorg Delle-KarthRudolf BergerKurt HuberUta HoppeRobert ZweikerRonald DickPatrick CarrollMark SaderGregory StarmerPaul GarrahySteven G.M. CoverdaleConstantine AroneySam LehmanOwen RaffelPhilip Roberts-ThomsonRomulo Oqueli FloresDavid ColquhounJames RogersDaniel NinioJohn HorowitzMargaret ArstallJames ShawChris L.S. HiiAllan SowardNicholas CollinsJonathon WaitesSusana LloisOsvaldo CostamagnaGerardo ZapataSilvia SaavedraJorge GiordanoHugo LuquezHoracio CestariRuben Garcia DuranMario BerliGabriel WaismanHector LuciardiVictorino FuentealbaAlberto LibermanHugo ColomboEduardo D.S. BlumbergSebastian NaniMiguel Bustamante LabartaDaniela Garcia BrascaJuan Medrano AllendePablo GuzmanGabriela CarneroMarisa VicoRicardo DranMaria GiulianoCesar ZaidmanCristian PatocchiFederico NovoaRodolfo Ahuad GuerreroJulio VallejosAdrian HrabarJulio O.E. 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Asita de SilvaJosé TuñónAnthony DalbyZlatko FrasJan MurinTerrance ChuaArsen RisticYuri KarpovMaria DorobantuJoao MoraisAndrzej BudajRoger Correa FloresSigrun HalvorsenMarco AlingsGabriel Arturo Ramos LópezKhalid YusoffSasko KedevAleksandras LauceviciusAndrejs ErglisSang-Hyun KimHyo Soo KimTakeshi KimuraMarco ValgimigliDoron ZahgerDenis XavierRobert Gabor KissHung-Fat TsePablo Carlos Montenegro ValdovinosEvangelos LiberopoulosNicolas DanchinNikolaus MarxVakhtang ChumburidzeMarkku NieminenMargus ViigimaaPetr OstadalZeljko ReinerIvan PećinPatricio López-JaramilloHuo YongJuan-Carlos PrietoNina GotchevaRenato LopesMirza DilicPeter SinnaeveHeinz DrexelPhilip AylwardJean-François TambyWilliam SasielaAngèle MoryusefGuillaume LecorpsCorinne HanotinJay EdelbergKenneth MahaffeyMatthew RoePierluigi TricociAndreas ZeiherRobert HarringtonJ. Wouter JukemaPhilippe Gabriel StegHarvey WhiteRobert PordyGaren ManvelianMegan LoyJ Wouter JukemaShaun GoodmanRafael DiazDeepak BhattVera BittnerMichael SzarekGregory Schwartz
• Organismes : Centre Hospitalier Régional Universitaire [Montpellier] Auckland City Hospital Regeneron Pharmaceuticals [Tarrytown, NY] Regeneron Pharmaceuticals [Tarrytown, NY] Sanofi Bridgewater Leiden University Medical Center [Leiden] University of Alberta St. Michael's Hospital ECLAEstudios Clínicos Latino América & Instituto Cardiovascular de Rosario), Rosario, Argentina Brigham & Women’s Hospital [Boston] University of Alabama [Birmingham] University of Colorado Anschutz Medical Campus [Aurora] Clinical Research Center State University of New York University of Colorado Anschutz Medical Campus [Aurora]
• Publié dans Diabetes Care le 01/11/2020

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Résumé : OBJECTIVE In observational data, lower levels of lipoprotein(a) have been associated with greater prevalence of type 2 diabetes. Whether pharmacologic lowering of lipoprotein(a) influences incident type 2 diabetes is unknown. We determined the relationship of lipoprotein(a) concentration with incident type 2 diabetes and effects of treatment with alirocumab, a PCSK9 inhibitor. RESEARCH DESIGN AND METHODS In the ODYSSEY OUTCOMES trial alirocumab was compared with placebo in patients with acute coronary syndrome. Incident diabetes was determined from laboratory, medication, and adverse event data. RESULTS Among 13,480 patients without diabetes at baseline, 1,324 developed type 2 diabetes over a median 2.7 years. Median baseline lipoprotein(a) was 21.9 mg/dL. With placebo, 10 mg/dL lower baseline lipoprotein(a) was associated with hazard ratio 1.04 (95% CI 1.02−1.06, P < 0.001) for incident type 2 diabetes. Alirocumab reduced lipoprotein(a) by a median 23.2% with greater absolute reductions from higher baseline levels and no overall effect on incident type 2 diabetes (hazard ratio 0.95, 95% CI 0.85–1.05). At low baseline lipoprotein(a) levels, alirocumab tended to reduce incident type 2 diabetes, while at high baseline lipoprotein(a) alirocumab tended to increase incident type 2 diabetes compared with placebo (treatment–baseline lipoprotein(a) interaction P = 0.006). In the alirocumab group, a 10 mg/dL decrease in lipoprotein(a) from baseline was associated with hazard ratio 1.07 (95% CI 1.03−1.12; P = 0.0002) for incident type 2 diabetes. CONCLUSIONS In patients with acute coronary syndrome, baseline lipoprotein(a) concentration associated inversely with incident type 2 diabetes. Alirocumab had neutral overall effect on incident type 2 diabetes. However, treatment-related reductions in lipoprotein(a), more pronounced from high baseline levels, were associated with increased risk of incident type 2 diabetes. Whether these findings pertain to other therapies that reduce lipoprotein(a) is undetermined.

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