Philippe JEAN-PIERRE

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• Type de publi. : Article dans une revue
• Date de publi. : 02/03/2021
• Auteurs : Bernard VanhoveOdile DuvauxJuliette RoussePierre‐joseph RoyerGwénaëlle EvannoCarine CironElsa LheriteauLaurent VacherNadine GervoisRomain OgerYannick JacquesSophie ConchonApolline SalamaRoberto DuchiIrina LagutinaAndrea PerotaPhilippe DelahautMatthieu LedureMelody PaulusRay T SoChris Ka‐pun MokRoberto BruzzoneMarc BouilletSophie BrouardEmanuele CozziCesare GalliDominique BlanchardJean‐marie BachJean‐paul Soulillou
• Organismes : Xenothera [Nantes, France] Xenothera [Nantes, France] Xenothera [Nantes, France] Xenothera [Nantes, France] Xenothera [Nantes, France] Xenothera [Nantes, France] Xenothera [Nantes, France] Xenothera [Nantes, France] Anti-Tumor Immunosurveillance and Immunotherapy Anti-Tumor Immunosurveillance and Immunotherapy Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications Centre de Recherche en Transplantation et Immunologie Xenothera [Nantes, France] Avantea [Cremona, Italy] Avantea [Cremona, Italy] Avantea [Cremona, Italy] CER Groupe CER Groupe CER Groupe The University of Hong Kong The University of Hong Kong The University of Hong Kong Xenothera [Nantes, France] Centre de Recherche en Transplantation et Immunologie Azienda Ospedale Università di Padova = Hospital-University of Padua Avantea [Cremona, Italy] Xenothera [Nantes, France] Immuno-Endocrinologie Cellulaire et Moléculaire Centre de Recherche en Transplantation et Immunologie
• Publié dans European Journal of Immunology le 22/10/2020

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Résumé : Heterologous polyclonal antibodies might represent an alternative to the use of convalescent plasma or monoclonal antibodies (mAbs) in coronavirus disease (COVID-19) by targeting multiple antigen epitopes. However, heterologous antibodies trigger human natural xenogeneic antibody responses particularly directed against animal-type carbohydrates, mainly the N-glycolyl form of the neuraminic acid (Neu5Gc) and the α1,3galactose, potentially leading to serum sickness or allergy. Here, we immunized cytidine monophosphate-N-acetylneuraminic acid hydroxylase and α1,3-galactosyl-transferase (GGTA1) double KO pigs with the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor binding domain to produce glyco-humanized polyclonal neutralizing antibodies lacking Neu5Gc and α1,3-galactose epitopes. Animals rapidly developed a hyperimmune response with anti-SARS-CoV-2 end-titers binding dilutions over one to a million and end-titers neutralizing dilutions of 1:10 000. The IgG fraction purified and formulated following clinical Good Manufacturing Practices, named XAV-19, neutralized spike/angiotensin converting enzyme-2 interaction at a concentration <1 μg/mL, and inhibited infection of human cells by SARS-CoV-2 in cytopathic assays. We also found that pig GH-pAb Fc domains fail to interact with human Fc receptors, thereby avoiding macrophage-dependent exacerbated inflammatory responses and a possible antibodydependent enhancement. These data and the accumulating safety advantages of using GH-pAbs in humans warrant clinical assessment of XAV-19 against COVID-19.

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Fichiers liés : VanhoveEq3.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 02/03/2021
• Auteurs : Valérie GounantMichaël DuruisseauxGhassen SoussiSylvie van HulstBertrand DautzenbergJacques CadranelMarie WislezJean TrédanielJean-Philippe SpanoCarole HelisseyChristos ChouaïdOlivier MolinierXavier DhalluinLudovic DoucetJosé HureauxAurélie CazesGérard Zalcman
• Organismes : Service d’oncologie thoracique et essais précoces [CHU Bichat] Hôpital Louis Pradel [CHU - HCL] Centre de Recherche en Cancérologie de Lyon Service d’oncologie thoracique et essais précoces [CHU Bichat] Centre Hospitalier Universitaire de Nîmes Hopital d'instruction des armées Sainte-Anne [Toulon] CHU Tenon [AP-HP] AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris] Centre hospitalier Saint-Joseph [Paris] Institut Pierre Louis d'Epidémiologie et de Santé Publique Hôpital d'Instruction des Armées Begin [Saint-Mandé, France] Centre Hospitalier Intercommunal de Créteil IMRB - CEPIA/"Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health" [Créteil] Centre Hospitalier Le Mans (CH Le Mans) Service d'oncologie médicale (CHRU Lille) Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris] Centre Hospitalier Universitaire d'Angers CIC - CHU Bichat Service d’oncologie thoracique et essais précoces [CHU Bichat]
• Publié dans Cancers le 21/10/2020

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Résumé : Anti-PD-1 antibodies prolong survival of performance status (PS) 0–1 advanced non-small-cell lung cancer (aNSCLC) patients. Their efficacy in PS 3–4 patients is unknown. Conse- cutive PS 3–4 aNSCLC patients receiving compassionate nivolumab were accrued by 12 French thoracic oncology departments, over 24 months. Overall survival (OS) was calculated using the Kaplan-Meier method. Prognostic variables were assessed using Cox proportional hazards models. Overall, 35 PS 3–4 aNSCLC patients (median age 65 years) received a median of 4 nivolumab infusions (interquartile range [IQR], 1–7) as first- (n = 6) or second-line (n = 29) therapy. At a median of 52-month follow-up (95%CI, 41–63), 32 (91%) patients had died. Median progression-free survival was 2.1 months (95%CI, 1.1–3.2). Median OS was 4.4 months (95%CI, 0.5–8.2). Overall, 20% of patients were alive at 1 year, and 14% at 2 years. Treatment-related adverse events occurred in 8/35 patients (23%), mostly of low-grade. After adjustment, brain metastases (HR = 5.2; 95%CI, 9–14.3, p = 0.001) and <20 pack-years (HR = 4.8; 95%CI, 1.7–13.8, p = 0.003) predicted worse survival. PS improvement from 3–4 to 0–1 (n = 9) led to a median 43-month (95%CI, 0–102) OS. Certain patients with very poor general condition could derive long-term benefit from nivolumab salvage therapy.

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Fichiers liés : cancers-13-01040-v4.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 02/03/2021
• Auteurs : Philippe Raynaud
• Organismes : Institut Michel Villey pour la Culture Juridique et la Philosophie du Droit
• Publié dans Commentaire le 29/10/2020

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Résumé : La comparaison entre Emmanuel Macron et Valéry Giscard d’Estaing a été souvent faite et elle conduit assez naturellement à s’interroger sur la viabilité en France d’une politique « centriste » que beaucoup considèrent sinon comme foncièrement illégitime, du moins comme inadaptée à la culture politique française. Pour la droite comme pour la gauche, le centre n’est rien d’autre que l’éternel « marais », peuplé de « ventres mous » ou de « mollassons » à jamais incapables d’être plus que des « supplétifs » d’un des deux courants fondamentaux. Les plus bienveillants, comme Maurice Duverger, concèdent que les Français veulent peut-être être « gouvernés au centre », mais c’est pour ajouter que cela ne signifie pas qu’ils veuillent être gouvernés « par le centre ». Le grand intérêt du livre vif et enlevé de Jean-Pierre Rioux est de prendre le problème de front, en s’attachant au contraire à montrer le rôle important et parfois décisif joué, dans l’histoire politique française, par des hommes politiques d’inspirations diverses, qui « ont été depuis plus de deux siècles à contre-pied de « « la » droite comme de « la » gauche », du conservatisme aveugle, du progressisme délirant et de l’appel au peuple vengeur » et dont la « coalition » a tenté de « réconcilier le pouvoir, les élites et le « peuple » pour faire avancer « le droit et la raison », et a contribué à différents moments de notre histoire à « remettre d’aplomb une France boiteuse » (p. 8-9). Pour cela, il s’est attaché à douze figures de la vie politique française de la Révolution (Mirabeau) à la période actuelle (Emmanuel Macron)…

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• Type de publi. : Article dans une revue
• Date de publi. : 01/03/2021
• Auteurs : Claire DupuisClément Le BihanDaniele MaubonLaure CalvetStéphane RucklyCarole SchwebelLila BouadmaElie AzoulayMuriel CornetJean-Francois TimsitRebecca Hamidfar-RoyMagalie CiroldiClichy Catherine Paugam-BurtzArnaud FoucrierJean Christophe NavellouMichel WolffJean-Francois TimsitLila BouadmaBruno MourvillierRomain SonnevilleSarah ChemamDidier GrusonBertrand SouweineAlexandre LautrettePierre Emmanuel CharlesRémi BruyereMaël HametBernard AllaouchicheChristian GuillaumeCharles-Eric BerJohanne ProthetThomas RimmeleLaurent ArgaudMarie SimonMartin CourRomain HernuSamir JaberBoris JungMathieu ConseilYannael CoiselFouad BelafiaKada KloucheLaurent AmiguesSonia MachadoMarianne ServeauxJean ChastreJean-Louis TrouilletJoël CoussonPascal RaclotThierry FlochFabrice ZeniMichael DarmonMatthias PichonMaud CoudrotSebastien NinetEric DiconneBenoit SchlemmerElie AzoulayVirginie LemialeNicolas MaziersFerhat MezianiDavid SchnellJulie Boisrame-HelmsRaluca Neagu-AncaXavier DelabrancheOlivier MartinetMaité Garrouste-OrgeasBenoit MissetFabrice BruneeVirginie LaurentGuillaume LacaveJean-Pierre BedosKhadija HammiLenka StyfalovaJoelle FritzschSophie LetrouLucie EstevezTherese DevauxCeline DubienSoumia BayarassouCatherine Jouvene FaureSylvie de La SalleAlbert PradesAnnie RodriguezPierre MeurMagda WarcholHanane El HaouariIgor TheodoseJulien FournierSebastien CavelotLilia Bakir KodjaMarie Joyeux-FaureFrédéric TaccoSonia RoosKarima DupreMalek AbazidMichele EssertPhilippe ArnaudEmmanuelle PapyBellabes GhezzoulOlivier GerbouinSandrine Corny PeccouxPhilippe FagnoniAnne MillaretChristine PivotCecile GerardCyril BreukerAudrey CastetFanny CharbonnierMaryline LegrandJulia MordiniIsabelle Madeleine ChambrinAnne Hutt ClaussMohamed CherifiAnne PattynMuriel CornetDanièle MaubonEliane BenvenisteFrédéric GrenouilletChristian ChochillonIsabelle AccoberryDenis PonsNatacha MrozekFrédéric DalleStephane PicotFrancoise BeyerleAnne-Lise BienvenuNathalie BourgeoisArnaud FekkarDominique ToubasHélène RaberinErmanno CandolfiValérie BruMarie Dominique KitzisYaye SenghorCatherine PaletteStéphane RucklyAurélien VesinJean-Paul MiraJean-Ralph ZaharDominique LarreyJean-Pierre ZarskiJean-Ralph ZaharJean-Paul MiraDominique LarreyJean-Pierre ZarskiEdith Schir
• Organismes : CHU Gabriel Montpied [Clermont-Ferrand] Unité de Nutrition Humaine Infection, Anti-microbiens, Modélisation, Evolution Centre Hospitalier Régional Universitaire [Montpellier] Centre Hospitalier Universitaire [CHU Grenoble] Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 Translational microbial Evolution and Engineering CHU Clermont-Ferrand Université de Paris, IAME, INSERM, Paris, France Hôpital Michallon Université Grenoble Alpes Infection, Anti-microbiens, Modélisation, Evolution AP-HP - Hôpital Bichat - Claude Bernard [Paris] Hopital Saint-Louis [AP-HP] Translational microbial Evolution and Engineering Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 Centre Hospitalier Universitaire [CHU Grenoble] Université de Paris, IAME, INSERM, Paris, France Unité de soins intensifs médicaux et infectieux [AP-HP Hôpital Bichat-Claude-Bernard] Clinique de réanimation médicale Hôpital Beaujon [AP-HP] Service de Réanimation médicale [CHRU Besançon] Université Paris Diderot - Paris 7 AP-HP - Hôpital Bichat - Claude Bernard [Paris] Université de Paris, IAME, INSERM, Paris, France Unité de soins intensifs médicaux et infectieux [AP-HP Hôpital Bichat-Claude-Bernard] Infection, Anti-microbiens, Modélisation, Evolution AP-HP - Hôpital Bichat - Claude Bernard [Paris] Hôpital universitaire Robert Debré [Reims] Université de Reims Champagne-Ardenne AP-HP - Hôpital Bichat - Claude Bernard [Paris] CHU Trousseau [APHP] Centre Hospitalier Universitaire [CHU Grenoble] Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 Translational microbial Evolution and Engineering Centre Hospitalier Universitaire [CHU Grenoble] Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 Translational microbial Evolution and Engineering
• Publié dans Open Forum Infectious Diseases le 22/10/2020

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Résumé : Abstract Background We aimed to assess the prognostic value of repeated measurements of serum (1–3)-β-D-glucan (BDG), mannan-antigen (mannan-Ag), and antimannan antibodies (antimannan-Ab) for the occurrence of invasive candidiasis (IC) in a high-risk nonimmunocompromised population. Methods This was a preplanned ancillary analysis of the EMPIRICUS Randomized Clinical Trial, including nonimmunocompromised critically ill patients with intensive care unit–acquired sepsis, multiple Candida colonization, and multiple organ failure who were exposed to broad-spectrum antibacterial agents. BDG (>80 and >250 pg/mL), mannan-Ag (>125 pg/mL), and antimannan-Ab (>10 AU) were collected repeatedly. We used cause-specific hazard models. Biomarkers were assessed at baseline in the whole cohort (cohort 1). Baseline covariates and/or repeated measurements and/or increased biomarkers were then studied in the subgroup of patients who were still alive at day 3 and free of IC (cohort 2). Results Two hundred thirty-four patients were included, and 215 were still alive and free of IC at day 3. IC developed in 27 patients (11.5%), and day 28 mortality was 29.1%. Finally, BDG >80 pg/mL at inclusion was associated with an increased risk of IC (CSHR[IC], 4.67; 95% CI, 1.61–13.5) but not death (CSHR[death], 1.20; 95% CI, 0.71–2.02). Conclusions Among high-risk patients, a first measurement of BDG >80 pg/mL was strongly associated with the occurrence of IC. Neither a cutoff of 250 pg/mL nor repeated measurements of fungal biomarkers seemed to be useful to predict the occurrence of IC. The cumulative risk of IC in the placebo group if BDG >80 pg/mL was 25.39%, which calls into question the efficacy of empirical therapy in this subgroup.

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Fichiers liés : 2021 Dupuis et al., Open Forum Infect Dis.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/03/2021
• Auteurs : Merwan MokhtariPhilippe Pagnod-RossiauxChristophe LevalloisFrancois LaruelleDaniel T CassidyMauro BettiatiJean-Pierre Landesman
• Organismes : Institut de Physique de Rennes 3SP Technologies Institut des Fonctions Optiques pour les Technologies de l'informatiON 3SP Technologies McMaster University [Hamilton, Ontario] 3SP Technologies Institut des Fonctions Optiques pour les Technologies de l'informatiON
• Publié dans Applied Physics Letters le 01/11/2020

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Résumé : We report an investigation of the strain field in mesa structures for oxide-confined vertical-cavity surface-emitting lasers (VCSELs) using the polarization-resolved micro-photoluminescence (PL) measurement of the degree of polarization (DOP) at room temperature. The DOP of the PL is correlated with the spatial distribution of the embedded anisotropic strain in a VCSEL structure. Measurements normal to (100) surfaces of the samples and from (110) cross-sectional planes were performed. The effect of two processes required in the fabrication of GaAs-based VCSELs was studied: the plasma etching of the P-doped distributed Bragg reflector and the wet oxidation process used to control current flow and lateral optical confinement. The DOP method allows very sensitive measurements of the mechanical strain (on the order of 10 - 5) accumulated in VCSEL devices even during different steps of the fabrication process.

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Fichiers liés : Mechanical strain mapping of GaAs based VCSELs.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/03/2021
• Auteurs : Tania PetersenThibault MahévasPauline CannetJean-David BouazizCamille HuaCharles ZarnitskyPhilippe ModianoFrançois LifermannBruno SassolasOlivier CarpentierArsène MékinianLaurent GarderetPierre AucouturierYannick Chantran
• Organismes : CHU Saint-Antoine [AP-HP] Centre de Recherche Saint-Antoine CHU Saint-Antoine [AP-HP] CHU Saint-Antoine [AP-HP] Centre de Recherche Saint-Antoine Service de Dermatologie [AP-HP Hôpital Saint-Louis] Service de dermatologie [Mondor] Epidemiology in Dermatology and Evaluation in Therapeutics Groupe Hospitalier du Havre Hôpital Jacques Monod (MONTIVILLIERS) Hôpital Saint Vincent de Paul [Lille] Centre Hospitalier de Dax Hôpital de la Cavale Blanche - CHRU Brest Hôpital Provo CHU Saint-Antoine [AP-HP] CHU Pitié-Salpêtrière [AP-HP] CHU Saint-Antoine [AP-HP] Centre de Recherche Saint-Antoine CHU Saint-Antoine [AP-HP] Centre de Recherche Saint-Antoine
• Publié dans Clinical Laboratory le 31/10/2020

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Résumé : Background: Scleromyxedema (SME) is a rare mucinosis associated with monoclonal gammopathy. Several biochemical peculiarities of monoclonal immunoglobulins (Ig) in SME patients were reported in case reports or short series, such as IgGλ over-representation, cationic migration, and partial deletion. Methods: Monoclonal immunoglobulins (Ig) from the serum of 12 consecutive patients diagnosed with scleromyxedema (SME) were analyzed using electrophoretic and immunoblotting techniques. Results: All monoclonal Ig from 12 SME were of IgG1 subclass, with an overrepresentation of the lambda-type light chain and a cationic mobility on standard zone electrophoresis, as compared with 21 cases of monoclonal gammopathy of undetermined significance (MGUS) of IgG1 subclass. Reactivity with specific monoclonal antibodies demonstrated no evident deletion of the heavy chain constant domains, which was also confirmed by analysis of Ig heavy chain molecular weight on a purified monoclonal component from one case. Conclusions: Significant isotype restriction of both heavy and light chains, and peculiar biochemical properties suggest that monoclonal Ig might be involved in pathophysiological events of SME.

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Fichiers liés : #200605 Petersen et al 2020 manuscript revised1_DHO pa final.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/03/2021
• Auteurs : Marco PappaccogliSilvia Di MonacoEwa Warchoł-CelińskaAurélien LorthioirLaurence AmarLucas AparicioChristophe BeauloyeRosa Maria BrunoPatrick ChenuPeter de LeeuwTine de BackerPhilippe DelmotteZivka DikaDaniel GordinHilde HeutenYoshio IwashimaJean-Marie KrzesinskiAbraham KroonLucia MazzolaiEsteban PochPantelis A. SarafidisChristophe SeinturierWilko SpieringL ToubianaPatricia van Der NiepenDaan van TwistAdriana VisonàJean-Claude WautrechtHelena WitowiczJianzhong XuAleksander PrejbiszAndrzej JanuszewiczAnne BlanchardAlexandre PersuFrank HammerPierre GoffetteParla AstarciAndré PeetersRobert VerhelstMiikka VikkulaFrank van TussenbroekSofie GevaertDimitri HemelsoetLuc DefreyneLaetitia YperzeeleThijs van Der ZijdenJean-Philippe LengeléMuriel SpryngerPeter VerhammeThomas VanasschePasquale ScoppettuoloWouter VinckVassilev DobrinYaneva TeodoraJiguang WangBojan JelakovićIlkka TikkanenMaarit VenermoR MäkeläPierre-François PlouinXavier JeunemaitreAntoine ChédidElie MousseauxOlivier OrmezzanoChristopher SeinturierFrédéric ThonyFelix MahfoudSaarraaken KulenthiranAlexia PiperidouMichael DoumasGeorge StergiouDemetrios VlahakosCaitriona CanningYehonatan SharabiAlberto MorgantiStefano TaddeiCaterina RomaniniIlaria PetrucciFranco RabbiaGian Paolo RossiSilvia LercoPietro MinuzGiancarlo MansuetoSergio de MarchiDenise MarconPatrizia SalicePaola BigolinViviana ZingarettiRosario CianciMarialuisa ZeddeMaria Chiara MatteucciOsami KawaradaYoshito KadoyaBram KroonBert-Jan van den BornAud HøieggenMartin Skage SommerAdam WitkowskiJacek KądzielaAleksandra SoplińskaKrzysztof PieluszczakKatarzyna Jóżwik-PlebanekMagdalena JanuszewiczElżbieta FlorczakPiotr DobrowolskiEva SzabóováMarek HudákMatej MoščovičJuan Diego MediavillaFernando Jaen AguilaAnna OliverasJulian SeguraJose PradoNicolas Roberto RoblesEnrique Montagud-MarrahiAlicia MolinaElena GuillenMarta BurrelPatricia Fernàndez de La LlamaAntonio Barros-MembrillaAnders GottsäterGregor WuerznerGiacomo BusoFaiçal JarrayaHanen ChakerDavid AdlamConstantina ChrysochouNeeraj DhaunRobert HunterIain MacintyreDavid Webb
• Organismes : CIC - HEGP
• Publié dans Cardiovascular Research le 29/10/2020

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Résumé : Abstract Aims Since December 2015, the European/International Fibromuscular Dysplasia (FMD) Registry enrolled 1022 patients from 22 countries. We present their characteristics according to disease subtype, age and gender, as well as predictors of widespread disease, aneurysms and dissections. Methods and results All patients diagnosed with FMD (string-of-beads or focal stenosis in at least one vascular bed) based on computed tomography angiography, magnetic resonance angiography, and/or catheter-based angiography were eligible. Patients were predominantly women (82%) and Caucasians (88%). Age at diagnosis was 46 ± 16 years (12% ≥65 years old), 86% were hypertensive, 72% had multifocal, and 57% multivessel FMD. Compared to patients with multifocal FMD, patients with focal FMD were younger, more often men, had less often multivessel FMD but more revascularizations. Compared to women with FMD, men were younger, had more often focal FMD and arterial dissections. Compared to younger patients with FMD, patients ≥65 years old had more often multifocal FMD, lower estimated glomerular filtration rate and more atherosclerotic lesions. Independent predictors of multivessel FMD were age at FMD diagnosis, stroke, multifocal subtype, presence of aneurysm or dissection, and family history of FMD. Predictors of aneurysms were multivessel and multifocal FMD. Predictors of dissections were age at FMD diagnosis, male gender, stroke, and multivessel FMD. Conclusions The European/International FMD Registry allowed large-scale characterization of distinct profiles of patients with FMD and, more importantly, identification of a unique set of independent predictors of widespread disease, aneurysms and dissections, paving the way for targeted screening, management, and follow-up of FMD.

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• Type de publi. : Article dans une revue
• Date de publi. : 01/03/2021
• Auteurs : Laure LacanNacim BetrouniM. D. LamblinL. ChatonArnaud DelvalJ. L. BourriezLaurent StormePhilippe DerambureSylvie Nguyen The Tich
• Organismes : Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 Evaluation des technologies de santé et des pratiques médicales - ULR 2694 Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837
• Publié dans Neurophysiologie Clinique = Clinical Neurophysiology le 01/11/2020

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Résumé : AbstractObjectivesTo identify relevant quantitative parameters for early classification of neonatal hypoxic-ischemic encephalopathy (HIE) severity from conventional EEGs.MethodsNinety EEGs, recorded in full-term infants within 6 h of life after perinatal hypoxia, were visually classified according to the French EEG classification into three groups of increasing HIE severity.Physiologically significant EEG features (signal amplitude, continuity and frequency content) were automatically quantified using different parameters. The EEG parameters selection was based on their ability to reproduce the visual EEG classification. Post hoc analysis based on clinical outcome was performed.ResultsSix EEG parameters were selected, with overall EEG classification performances between 61% and 70%. All parameters differed significantly between group 3 (severe) and groups 1 (normal-mildly abnormal) and 2 (moderate) EEGs (p < 0.001). Amplitude and discontinuity parameters were different between the 3 groups (p < 0.01) and were also the best predictors of clinical outcome. Conversely, pH and lactate did not differ between groups.DiscussionThis study provides quantitative EEG parameters that are complementary to visual analysis as early markers of neonatal HIE severity. These parameters could be combined in a multiparametric algorithm to improve their classification performance. The absence of relationship between pH lactate and HIE severity reinforces the central role of early neonatal EEG.

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Fichiers liés : S0987705320301477.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/03/2021
• Auteurs : Tim HarrisonPascal ChanezFrancesco MenzellaGiorgio Walter CanonicaRenaud LouisBorja CosioNjira LugogoArjun MohanAnnie BurdenLawrence McdermottEsther Garcia GilJames ZangrilliWolfgang PohlRobert VovesMaud DeschampheleireJean-Benoit MartinotRudi PechéKenneth ChapmanAmarjit CheemaDelbert DorscheidJ. Mark FitzgeraldRemi GagnonWilliam Patrick KillornRonald OlivensteinGeorge PhilteosClare RamseyJ. Douglass RolfBrandie WalkerOle HilbergTina SkjoldIngrid TitlestadAuli HakulinenMaritta KilpeläinenMichèle Ben HayounPhilippe BonniaudArnaud BourdinFrédéric de BlayGaëtan DesleeGilles DevouassouxAlain DidierYoucef DouadiStéphanie FryGilles GarciaPierre-Olivier GirodetChristophe LeroyerAntoine MagnanGuillaume MahayCécilia NocentChristophe PisonPauline-Marie RouxCamille TailléJuliana-Angelica TiotiuEkkehard BeckMargret JandlChristian KaehlerFrank KässnerFrank KoestersJuliane KronsbeinThomas SchaumChristian SchulzDirk SkowaschChristian TaubeTobias WelteAndrés de RouxBianca BeghéFrancesco BlasiGiovanna CarpagnanoCristiano CarusoAngelo Guido CorsicoElio ConstantinoNunzio CrimiPiero MaestrelliManlio MilaneseAlberto PapiGirolamo PelaiaLaura PiniPierachille SantusEleonora SaviNicola ScichiloneGianenrico SennaGiuseppe SpadaroAdriano VaghiSteven GansJurgen HöltersB. LangeveldWillem PietersG.H.A. StaaksIlonka van VeenJ.W.K. van den BergGunnar EinvikSverre LehmannIsmael Ali GarcíaCarlos AlmonacidIrina BoboleaPaloma Campo MozoGustavo de LuizChristian Domingo RibasJosé María Echave-Sustaeta María-ToméJuan Luis García RiveroBorja García-Cosío PiquerasAna Gómez-Bastero FernándezRuperto González PérezAythamy Henríquez SantaCarlos Martínez RiveraXavier Muñoz GallJacinto RamosJose Gregorio Soto CamposCarmen Vidal PanNikolai StenforsAlf TunsäterInes VingeRekha ChaudhuriTimothy HarrisonAdel MansurShuaib NasserMonica NordstromPaul PfefferDinesh SaralayaPhilip ShortArun AdlakhaOral AlpanFrancis AverillAnil BadhwarJose BardelasBarbara BaxterGeorge BenschWilliam BergerJonathan BernsteinTracy BridgesRyan BrimeyerWilliam CalhounEdward CampbellWilliam Brett CherryGeoffrey ChuppLee CloreJohn CohnJeremy ColeJohn CondemiJames CuryBenjamin DavisSamuel DeleonLuis DelacruzJoseph DiazDavid ErbEmeka EziriFaisal FakihDouglas FiedlerDavid FostStephen FritzErika GonzalezBrad GoodmanPeter GottliebGregory GottschlichRichard GowerRizan HajalJames HarrisHengameh Heidarian-RaissyAlbrecht HeyderDavid HillFernando HolguinIftikhar HussainJonathan IllowiteJoshua JacobsMikell JarrattHarold KaiserNeil KaoRavindra KashyapDavid KaufmanEdward KentKenneth KimRyan KleinMonica KraftRitsu KonoShahrukh KureishyJeffrey LefleinMila LeongHuamin LiRobert LinMichael MarcusDiego Jose Maselli CaceresVinay MehtaCurtis MelloMark MillardAaron MilstoneWendy MooreMark MossNayla MumnehThomas O'BrienDavid OstranskyMichael PalumboPurvi ParikhSudhir ParikhAmit PatelGuido PerezWarren PleskowBruce PrennerDileep PuppalaJohn RameyJoan ReibmanRamon ReyesEmory RobinetteIleana RodicioStephen RyanSudhir SekhsariaBarry SigalVinay SikandWeily SoongSelwyn SpangenthalRoy St. JohnGary StevenVijay SubramaniamKaharu SuminoEric SztejmanRicardo TanTonny TanusCharles ThompsonCarl ThornbladeManuel VillarealSally WenzelHeidi ZafraTomasz Ziedalski
• Organismes :
• Publié dans The Lancet Respiratory Medicine le 23/10/2020

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Résumé : Background: ANDHI was done to assess the efficacy of benralizumab, including onset of effect and impact on health-related quality of life (HRQOL), exacerbation rate, lung function, and nasal polyposis symptoms. Methods: This phase 3b, randomised, double-blind, parallel-group, placebo-controlled ANDHI study was completed in adults (aged 18–75 years) with severe eosinophilic asthma with at least 2 exacerbations in the previous year, despite high-dose inhaled corticosteroid plus additional controllers, screening blood eosinophil counts of at least 150 cells per μL, and an Asthma Control Questionnaire 6 (ACQ-6) score of 1·5 or more. Patients who met eligibility criteria were randomly assigned (2:1; stratified by previous exacerbation count [two, or three or more], maintenance oral corticosteroid use, and region), using an integrated web-based response system, to receive benralizumab at 30 mg every 8 weeks (first three doses given 4 weeks apart) or matched placebo for 24 weeks. Primary efficacy measure was annualised asthma exacerbation rate, with rate ratio (RR) calculated over the approximate 24-week follow-up. Secondary efficacy measures included change from baseline to end of treatment (week 24) in St George's Respiratory Questionnaire (SGRQ) total score (key secondary endpoint), FEV1, peak expiratory flow (PEF), ACQ-6, Predominant Symptom and Impairment Assessment (PSIA), Clinician Global Impression of Change (CGI-C), Patient Global Impression of Change (PGI-C), and Sino-Nasal Outcome Test-22 (SNOT-22). All efficacy analyses, except for SNOT-22, were summarised and analysed using the full analysis set on an intention-to-treat population (all randomly assigned patients receiving investigational product, regardless of protocol adherence or continued participation in the study). SNOT-22 was summarised for the subgroup of patients with physician-diagnosed nasal polyposis with informed consent. This study is registered with ClinicalTrials.gov, NCT03170271. Findings: Between July 7, 2017, and Sept 25, 2019, 656 patients received benralizumab (n=427) or placebo (n=229). Baseline characteristics were consistent with severe eosinophilic asthma. Benralizumab significantly reduced exacerbation risk by 49% compared with placebo (RR estimate 0·51, 95% CI 0·39–0·65; p<0·0001) over the 24-week treatment period and provided clinically meaningful and statistically significant improvement from baseline to week 24 in SGRQ total score versus placebo (least squares mean change from baseline −8·11 (95% CI −11·41 to −4·82; p<0·0001), with similar differences at earlier timepoints. Benralizumab improved FEV1, PEF, ACQ-6, CGI-C, PGI-C, PSIA, and SNOT-22 at week 24 versus placebo, with differences observed early (within weeks 1 to 4). Adverse events were reported for 271 (63%) of 427 patients on benralizumab versus 143 (62%) of 229 patients on placebo. The most commonly reported adverse events for the 427 patients receiving benralizumab (frequency >5%) were nasopharyngitis (30 [7%]), headache (37 [9%]), sinusitis (28 [7%]), bronchitis (22 [5%]), and pyrexia (26 [6%]). Fewer serious adverse events were reported for benralizumab (23 [5%]) versus placebo (25 [11%]), and the only common serious adverse event (experienced by >1% of patients) was worsening of asthma, which was reported for nine (2%) patients in the benralizumab group and nine (4%) patients in the placebo group. Interpretation: Our results extend the efficacy profile of benralizumab for patients with severe eosinophilic asthma, showing early clinical benefits in patient-reported outcomes, HRQOL, lung function, and nasal polyposis symptoms

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Fichiers liés : 2021 Harrison et al., Onset of effect and impact.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 01/03/2021
• Auteurs : Sophie GarnierMagdalena HarakalovaStefan WeissMichal MokryVera Regitz-ZagrosekChristian HengstenbergThomas CappolaRichard IsnardEloisa ArbustiniStuart CookJessica van SettenJorg CalisHakon HakonarsonMichael MorleyKlaus StarkSanjay PrasadJin LiDeclan O'ReganMaurizia GrassoMartina Müller-NurasyidThomas MeitingerJean‐philippe EmpanaKonstantin StrauchMelanie WaldenbergerKenneth MarguilesChristine SeidmanGeorgios KararigasBenjamin MederJan HaasPierre BoutouyriePatrick LacolleyXavier JouvenJeanette ErdmannStefan BlankenbergThomas WichterVolker RuppertLuigi TavazziOlivier DubourgGérard RoizesRichard DorentPascal de GrooteLaurent FauchierJean-Noël TrochuJean-François AupetitZofia BilinskaMarine GermainUwe VölkerDaiane HemerichIbticem RajiDelphine Bacq-DaianCarole ProustPaloma RemiorManuel Gomez-BuenoKristin LehnertRenee MaasRobert OlasoGanapathi Varma SaripellaStephan FelixSteven McginnLaëtitia Duboscq-BidotAlain van MilCéline BesseVincent FontaineHélène BlanchéFlavie AderBrendan KeatingAngélique CurjolAnne BolandMichel KomajdaFrançois CambienJean‐françois DeleuzeMarcus DörrFolkert W AsselbergsEric VillardDavid-Alexandre TrégouëtPhilippe CharronCarl SemaanArthur CharbonnierJeremy PascoWalid DarwicheChristophe Saint EtienneXavier BailleulThierry BourguignonDenis AngoulvantFabrice IvanesThibaud Genet
• Organismes : Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases University Medical Center [Utrecht] Universität Greifswald = University of Greifswald German Center for Cardiovascular Research University Medical Center [Utrecht] Charité - UniversitätsMedizin = Berlin University Medicine German Center for Cardiovascular Research University of Pennsylvania [Philadelphia] Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases Istituti di Ricovero e Cura a Carattere Scientifico National Heart Centre Singapore University Medical Center [Utrecht] University Medical Center [Utrecht] Children’s Hospital of Philadelphia University of Pennsylvania [Philadelphia] Universität Regensburg = University of Regensburg = Université de Ratisbonne [Allemagne] Royal Brompton Hospital [London, United Kingdom] Children’s Hospital of Philadelphia Imperial College London Istituti Clinici Scientifici Maugeri [Pavia] Helmholtz Zentrum München = German Research Center for Environmental Health Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University CHU Trousseau [Tours] Éducation Éthique Santé Centre Hospitalier Régional Universitaire de Tours CHU Trousseau [Tours] Université de Tours CHU Trousseau [Tours] CHU Trousseau [Tours] Centre Hospitalier Régional Universitaire de Tours Transplantation, Immunologie, Inflammation [Tours] Transplantation, Immunologie, Inflammation [Tours] CHU Trousseau [Tours]
• Publié dans Journal of Clinical Medicine le 29/10/2020

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Résumé : Although many risk models have been tested in patients implanted by veno-arterial extracorporeal membrane oxygenation (VA-ECMO), few scores assessed patients’ prognosis in the setting of ST-segment elevation myocardial infarction (STEMI) with refractory cardiogenic shock. We aimed at assessing the performance of risk scores, notably the prEdictioN of Cardiogenic shock OUtcome foR AMI patients salvaGed by VA-ECMO (ENCOURAGE) score, for predicting mortality in this particular population. This retrospective observational study included patients admitted to Tours University Hospital for STEMI with cardiogenic shock and requiring hemodynamic support by VA-ECMO. Among the fifty-one patients, the 30-day and 6-month survival rates were 63% and 56% respectively. Thirty days after VA-ECMO therapy, probabilities of mortality were 12, 17, 33, 66, 80% according to the ENCOURAGE score classes 0–12, 13–18, 19–22, 23–27, and ≥28, respectively. The ENCOURAGE score (AUC of the Receiving Operating Characteristic curve = 0.83) was significantly better compared to other risk scores. The hazard ratio for survival at 30 days for each point of the ENCOURAGE score was 1.10 (CI 95% (1.06, 1.15); p < 0.001). Decision curve analysis indicated that the ENCOURAGE score had the best clinical usefulness of the tested risk scores and the Hosmer–Lemeshow test suggested an accurate calibration. Our data suggest that the ENCOURAGE score is valid and the most relevant score to predict 30-day mortality after VA-ECMO therapy in STEMI patients with refractory cardiogenic shock. It may help decision-making teams to better select STEMI patients with shock for VA-ECMO therapy.

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