Philippe JEAN-PIERRE

---

• Type de publi. : Article dans une revue
• Date de publi. : 01/11/2022
• Auteurs : Pierre NahonJessica Bamba-FunckRichard LayeseEric TrépoJessica Zucman-RossiCarole CagnotNathalie Ganne-CarriéCendrine ChaffautErwan GuyotMarianne ZiolAngela SuttonÉtienne AudureauPierre NahonTarik AsselahDominique GuyaderStanislas PolHélène FontaineGeorges-Philippe PageauxVictor de LédinghenDenis OuzanFabien ZoulimDominique RoulotAlbert TranJean-Pierre BronowickiThomas DecaensiGhassan RiachiPaul CalèsJean-Marie PéronLaurent AlricMarc BourlièrePhilippe MathurinSebastien DharancyJean-Frédéric BlancArmand AbergelOlivier ChazouillèresAriane MallatJean-Didier GrangéPierre AttaliLouis D’alterocheClaire WartelleThông DaoDominique ThabutChristophe PiletteChristine SilvainChristos ChristidisEric Nguyen-KhacBrigitte Bernard-ChabertSophie HillaireVincent Di MartinoNathalie Ganne-CarriéCendrine ChaffautIsabelle ArchambeaudLouis D’alterocheFrédéric ObertiDominique RoulotChristophe MorenoAlexandre LouvetThông DaoRomain MoirandOdile GoriaNicolas CarbonellJean-Charles Duclos-ValléeStanislas PolVictor de LedinghenViolaine OzenneJean HenrionJean-Marie PéronAlbert TranGabriel PerlemuterXavier AmiotJean-Pierre ZarskiSylvie ChevretNathalie BargetLucie del PozoSilvina Dos Reis Tavares
• Organismes : Centre de Recherche des Cordeliers CHU Amiens-Picardie Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 UPJV
• Publié dans Journal of Hepatology le 23/10/2020

---

Fichiers liés : S0168827822032949.pdf

---

Source

---

• Type de publi. : Article dans une revue
• Date de publi. : 31/10/2022
• Auteurs : Michel ZeitouniDavid SulmanJohanne SilvainMathieu KerneïsPaul GuedeneyOlivier BarthelemyDelphine BrugierPierre SabouretNiki ProcopiJean-Philippe ColletGilles Montalescot
• Organismes : CHU Pitié-Salpêtrière [AP-HP] Groupe Action Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
• Publié dans Heart le 30/10/2020

---

Résumé : Objective To determine if the changes in the European Society Cardiology/European Atherosclerotic Society (ESC/EAS) guidelines improved the identification for primary prevention therapy in young adults at risk of a premature myocardial infarction. Methods Patients admitted for a first ST-segment elevation myocardial infarction (STEMI) in the ePARIS registry (n=2757) between 2010 and 2018 were classified by age: <55, 55–65 and >65 years old. Using Systematic Coronary Risk Estimation 2, we evaluated whether patients would have been detected and treated with primary prevention statins before their first STEMI based on the 2021 EAS/ESC guidelines versus 2019 and 2016 guidelines. Eligibility for intensive proprotein convertase subtilisin/kexin type 9 (PCSK9i) in secondary prevention was also assessed. Results Following 2021 ESC guidelines, 62.5% of individuals aged <55 years old would have been eligible for statins before their first STEMI, similarly to older age categories. In comparison, only 17% and 18% of young individuals would have been eligible for primary prevention statins prior to their first STEMI with 2016 and 2019 guidelines, compared with group 55–65 years (41% and 35%) and >65 years old (19% and 72%), p<0.01. After their first STEMI, 25% of patients <55 years would be eligible for PCSK9i, compared with 23.2% and 15% in patients aged 55–65 years and >65 years. Conclusions The 2021 ESC guidelines allowed a much better detection of young individuals before their first STEMI than prior ESC guidelines. In secondary prevention, most of young individuals did not reach low-density lipoprotein cholesterol levels recommended, but only one quarter would be eligible for PCSK9i.

---

Source

---

• Type de publi. : Article dans une revue
• Date de publi. : 31/10/2022
• Auteurs : Justyna Elżbieta JońcaKatia FajerwergMyrtil L KahnPhilippe MeniniIzabela SówkaPierre Fau
• Organismes : Wrocław University of Science and Technology = Politechnika Wroclawska [Wrocław] Laboratoire de chimie de coordination Laboratoire de chimie de coordination Équipe MICrosystèmes d'Analyse Wrocław University of Science and Technology = Politechnika Wroclawska [Wrocław] Nanostructures et chimie organométallique (LPCNO) Laboratoire de chimie de coordination
• Publié dans Sensors & Transducers. le 22/10/2020

---

Résumé : Nanometer size p-n heterojunction has been created from CuO and ZnO anisotropic nanoparticles prepared by a one-pot organometallic approach. The method is based on the hydrolysis or oxidation of an adequate metal-organic precursors in pure octylamine. The CuO and ZnO nanostructures were dispersed in ethanol and then, mixed at different mass ratios, i.e. CuO(75%)/ZnO(25%), CuO(50%)/ZnO(50%) and CuO(25%)/ZnO(75%). Finally, the CuO and ZnO suspensions and their mixtures were deposited on miniaturized gas sensors substrates by an ink-jet printing method and heated up gradually to 550 o C in ambient air. Then, the as-prepared sensors have been exposed to CO (100 ppm), C 3 H 8 (100 ppm) and NH 3 (5 ppm) at different working temperatures (from 75 o C to 400 o C) and under 50 % of relative humidity (RH). Among all prepared sensors the one based on the mixture of CuO (75 %) and ZnO (25 %) presents a very sensitive and selective response to CO. Indeed, at the operating temperature of 165 o C, a high sensitivity towards CO was obtained (S CO =624 %). In these conditions, the sensor exhibited low sensitivity to other tested gases (K CO/C3H8 = 14.5 and K CO/NH3 = 26) but its response time was quite long (t 90 =2.3 min) and the recovery was very sluggish (t 10 > 20 min). Therefore, it was better to increase the working temperature up to 300 o C. Although the sensitivity and selectivity towards CO worsened (S CO =177%, K CO/C3H8 = 4.7 and K CO/NH3 = 9.8) the response/recovery time decreased to 50 s/4.5 min. The gas sensing performances of the CuO(75%)/ZnO(25%) composite was attributed to both high surface to volume ratio of the prepared nanostructures and the p-n heterojunction established between the CuO and ZnO nanoparticles.

---

Fichiers liés : Jonca_Towards Selective and Sensitive Detection of Carbon.pdf

---

Source

---

• Type de publi. : Communication dans un congrès
• Date de publi. : 31/10/2022
• Auteurs : Christina TampaktsiAnne-Laure GancelJean-Louis EscudierAlain SamsonHernan OjedaLucile PicJacques RousseauPhilippe GauthierDidier ViguierMaud-Isabeau FuretPierre Louis Teissedre
• Organismes : Unité de Recherche Œnologie [Villenave d'Ornon] Unité de Recherche Œnologie [Villenave d'Ornon] Unité de Recherche Œnologie [Villenave d'Ornon]

---

Résumé : The hybrids are new varieties that are resistant to the cryptogamic diseases of vines, and they may be a good solution to the reduction of pesticide use. However, these new varieties have appeared recently and only few studies have been conducted to check the quality of the wine that they produce. In this study, wines originated from hybrids were chemically characterized (polyphenols, tannins, anthocyanins, and color analysis). Results show that their oenological parameters were close to those of the Vitis vinifera wines. The wines made from Vinifera (100%), with Vidoc, and all the resistant Bouquets studied are malvidin-3 glucoside dominant, and all the others hybrids varieties are cyanidin dominant. Furthermore, the hybrid wines had a higher concentration in condensed tannins and a lower one in molecular tannins compared with the Vitis vinifera wines, except for the Vidoc wines. As far as the anthocyanin content is concerned, the samples contained anthocyanin diglucosides, with the malvidin-3,5-diglucoside (malvin) the most abundant one. Also, their concentration in molecular anthocyanins were higher than the concentration in normal wines. The Vidoc wines do not contain any malvin. For the other wines, malvin co-eluted with cyanidin-3-O-glucoside and in this case, the cyanidina s concentration was impressively higher than the Vidoc wines. The current OIV method gives different results for malvidol diglucoside compared to the use of an HPLC chromatography method (HPLC-DAD-QQQ). The current OIV method does not appear reliable in comparison with the HPLC method for detecting malvin. Finally, the hybrid wines had a darker blue/purplish color than the Vitis vinifera wines. © The Author(s), published by EDP Sciences

---

Fichiers liés : OENO_Bio_Web_Conf_2023_Tampaktsi.pdf

---

Source

---

• Type de publi. : Article dans une revue
• Date de publi. : 30/10/2022
• Auteurs : Pierre PhilouzeOlivier MalardSébastien AlbertLionel BadetBertrand BaujatFrédéric FaureCarine FuchsmannFranck JegouxJean Lacau-St-GuilyJean-Paul MarieAntoine RamadeS. VergezPhilippe CeruseOlivier J Gauthier
• Organismes : Hôpital de la Croix-Rousse [CHU - HCL] Centre Hospitalier Universitaire de Nantes = Nantes University Hospital AP-HP - Hôpital Bichat - Claude Bernard [Paris] Hôpital Edouard Herriot [CHU - HCL] CHU Tenon [AP-HP] Hôpital Edouard Herriot [CHU - HCL] Hôpital de la Croix-Rousse [CHU - HCL] Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou] CHU Tenon [AP-HP] CHU Rouen Hôpital de la Croix-Rousse [CHU - HCL] Centre Hospitalier Universitaire de Toulouse Hôpital de la Croix-Rousse [CHU - HCL] École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique Centre Hospitalier Universitaire Vétérinaire d'Oniris [Nantes]
• Publié dans Journal of Clinical Medicine le 29/10/2020

---

Résumé : Only three laryngeal transplants have been described in the literature to date, and none of the techniques has enabled a completely satisfactory functional result to be obtained. This article presents a new model of laryngeal transplantation, with quality of revascularisation of the transplant being the principal objective and optimisation of the various steps of the procedure, with the integration of a new reinnervation technique as a secondary objective. We present a preclinical animal study. Three pig larynges removed in vivo underwent allotransplantation according to the same protocol. The quality of the revascularisation was examined immediately after the surgery as well as by endoscopy for one animal on the fourth day after the operation. The mean time of cold ischaemia was 3 h 15 min. The anaesthetic tolerance of the pigs was excellent. Revascularisation was achieved and judged to be excellent for the three transplants immediately after the operation and the endoscopy performed for one pig on the fourth day after the operation confirmed this result. The anatomical similarities also enabled the application and integration of an innovative technique of laryngeal reinnervation into the various phases of the operation. We describe a reliable and reproducible animal model for laryngeal transplantation. Its application in humans can be envisaged.

---

Fichiers liés : jcm-11-06427.pdf

---

Source

---

• Type de publi. : Article dans une revue
• Date de publi. : 28/10/2022
• Auteurs : Jean RaymondJean-Christophe GentricElsa MagroLorena NicoEmma BacchusRuby KlinkChristophe CognardAnne-Christine JanuelJean-François SabatierDaniela IancuAlain WeillDaniel RoyMichel BojanowskiChiraz ChaalalaXavier BarreauVincent JeckoChrysanthi PapagiannakiStéphane DerreyEimad ShotarPhilippe CornuOmer EkerIsabelle Pelissou-GuyotatMichel PiotinSorin AldeaRémy BeaujeuxFrançois ProustRené AnxionnatVincent CostalatMarine Le CorreJean-Yves GauvritXavier MorandiHervé BrunelPierre-Hugues RocheThomas GraillonEmmanuel ChabertDenis HerbreteauHubert DesalDenis TrystramCharlotte BarbierThomas GaberelThanh NguyenGeraldine ViardGuylaine GevryTim DarsautCian O’kellyMichael ChowJ. Max FindlayJeremy RempelRobert FahedHoward LesiukBrian DrakeMarlene Dos SantosMichel NonentJulien OgnardMourad Cheddad El-AouniRomuald SeizeurSerge TimsitOlivier PradierRomain BoursierFrançois ThillaysVincent RoualdesRaphael BlancLionel CalviereJean Yves GauvritHélène RaoultFrançois EugeneAnthony Le BrasJean-Christophe FerreChristophe PayaIsabelle LecouillardElodie NouhaudThomas RonziereOlivier NaggaraChristine Rodriguez-RegentBasile KerlerouxEvelyne EmeryEmmanuel TouzeRoberto RivaIsabelle Pellisou-GuyotatJacques GuyotatMonsef BerhoumaChloé DumotAlessandra BiondiLaurent ThinesNassim BougaciGuillaume CharbonnierSerge BracardBenjamin GoryThierry CivitValérie Bernier-ChastagnerGaultier MarnatGuillaume PenchetEdouard GimbertAymeri HuchetGrégoire BoulouisRichard BibiHéloïse IferganKévin JanotStéphane VelutHadrien PeyriereJean-Marc KayaAdamou ToutaLucas TroudeSébastien BoissonneauFrédéric ClarençonNader SourourStéphanie LenckKévin PrematAnne-Laure BochAurélien NouetAlain BonafeCyril DargazanliGregory GascouPierre-Henri LefevreCarlos RiquelmeRaoul PopHélène CebulaIrène OllivierGiorgio SpatolaLaurent SpellVanessa ChalumeauSophie GallasLéon IkkaCristian MihaleaAugustin OzanneJildaz CaroffCharbel MounayerAymeric RouchaudFrançois CaireFrédéric RicolfiPierre ThouantCatherine CaoKlaus-Luc MourierWalid FarahMohamad AbdalkaderThien HuynhRabih TawkAndrew CarlsonLuciana Alves Oliveira SilvaNayara de Lima FroioGisele Sampaio SilvaFrancisco Mont’alverneJose Luri MartinsGeorge Nunes MendesRodrigo Rivera Miranda
• Organismes : Centre Hospitalier de l'Université de Montréal Service de Neuroradiologie [Brest] Université de Bretagne Occidentale - UFR Médecine et Sciences de la Santé - Brest Laboratoire de Traitement de l'Information Medicale Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] University of Alberta Centre Hospitalier de l'Université de Montréal Service Neuroradiologie Diagnostique et Thérapeutique [CHU Toulouse] Service Neuroradiologie Diagnostique et Thérapeutique [CHU Toulouse] Service Neurochirurgie [CHU Toulouse] Centre Hospitalier de l'Université de Montréal Centre Hospitalier de l'Université de Montréal Centre Hospitalier de l'Université de Montréal Université du Québec à Montréal = University of Québec in Montréal Centre Hospitalier de l'Université de Montréal Centre Hospitalier de l'Université de Montréal Centre Hospitalier Universitaire de Bordeaux Centre Hospitalier Universitaire de Bordeaux CHU Rouen Service de Neurochirurgie [CHU Rouen] Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau Institute for Research and Innovation in Biomedicine Centre d'Investigation Clinique [CHU Rouen] UNIROUEN - UFR Santé CHU Pitié-Salpêtrière [AP-HP] CHU Pitié-Salpêtrière [AP-HP] Service de neuroradiologie [Lyon] Hospices Civils de Lyon Centre Hospitalier de l'Université de Montréal
• Publié dans Journal of Neurosurgery le 26/10/2020

---

Résumé : Objective: The role of endovascular treatment in the management of patients with brain arteriovenous malformations (AVMs) remains uncertain. AVM embolization can be offered as stand-alone curative therapy or prior to surgery or stereotactic radiosurgery (SRS) (pre-embolization). The Treatment of Brain AVMs Study (TOBAS) is an all-inclusive pragmatic study that comprises two randomized trials and multiple registries. Methods: Results from the TOBAS curative and pre-embolization registries are reported. The primary outcome for this report is death or dependency (modified Rankin Scale [mRS] score > 2) at last follow-up. Secondary outcomes include angiographic results, perioperative serious adverse events (SAEs), and permanent treatment-related complications leading to an mRS score > 2. Results: From June 2014 to May 2021, 1010 patients were recruited in TOBAS. Embolization was chosen as the primary curative treatment for 116 patients and pre-embolization prior to surgery or SRS for 92 patients. Clinical and angiographic outcomes were available in 106 (91%) of 116 and 77 (84%) of 92 patients, respectively. In the curative embolization registry, 70% of AVMs were ruptured, and 62% were low-grade AVMs (Spetzler-Martin grade I or II), while the pre-embolization registry had 70% ruptured AVMs and 58% low-grade AVMs. The primary outcome of death or disability (mRS score > 2) occurred in 15 (14%, 95% CI 8%-22%) of the 106 patients in the curative embolization registry (4 [12%, 95% CI 5%-28%] of 32 unruptured AVMs and 11 [15%, 95% CI 8%-25%] of 74 ruptured AVMs) and 9 (12%, 95% CI 6%-21%) of the 77 patients in the pre-embolization registry (4 [17%, 95% CI 7%-37%] of 23 unruptured AVMs and 5 [9%, 95% CI 4%-20%] of 54 ruptured AVMs) at 2 years. Embolization alone was confirmed to occlude the AVM in 32 (30%, 95% CI 21%-40%) of the 106 curative attempts and in 9 (12%, 95% CI 6%-21%) of 77 patients in the pre-embolization registry. SAEs occurred in 28 of the 106 attempted curative patients (26%, 95% CI 18%-35%, including 21 new symptomatic hemorrhages [20%, 95% CI 13%-29%]). Five of the new hemorrhages were in previously unruptured AVMs (n = 32; 16%, 95% CI 5%-33%). Of the 77 pre-embolization patients, 18 had SAEs (23%, 95% CI 15%-34%), including 12 new symptomatic hemorrhages [16%, 95% CI 9%-26%]). Three of the hemorrhages were in previously unruptured AVMs (3/23; 13%, 95% CI 3%-34%). Conclusions: Embolization as a curative treatment for brain AVMs was often incomplete. Hemorrhagic complications were frequent, even when the specified intent was pre-embolization before surgery or SRS. Because the role of endovascular treatment remains uncertain, it should preferably, when possible, be offered in the context of a randomized trial. Trial registration: ClinicalTrials.gov NCT02098252.

---

Fichiers liés : Raymond2022.pdf

---

Source

---

• Type de publi. : Rapport
• Date de publi. : 28/10/2022
• Auteurs : Jean-Claude MalausaRomain BonafosSerge KreiterNicolas DesneuxJean-Claude OgierJean-Ulrich MullotChristian GauvritMarc BardinEnrique BarriusoPhilippe BernyM.-F. Corio-CostetJean-Pierre CugierMarc GallienSonia GrimbuhlerGuillermina Hernandez-RaquetFrançois LaurentLaure MamyPatrick SaindrenanJeanne StadlerBénédicte GautierChantal ArarRémy RossinLaurent ThibaultXavier TassusMarjorie MouetteSonia Grimbuhler
• Organismes : Institut Agro Montpellier Institut Agro Montpellier Institut Sophia Agrobiotech Diversité, Génomes & Interactions Microorganismes - Insectes [Montpellier] Service de Santé des Armées Unité de Pathologie Végétale Ecologie fonctionnelle et écotoxicologie des agroécosystèmes VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement Santé et agroécologie du vignoble Technologies et Méthodes pour les Agricultures de demain Toulouse Biotechnology Institute Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement Ecologie fonctionnelle et écotoxicologie des agroécosystèmes Direction de l'évaluation des produits réglementés Direction de l'évaluation des produits réglementés Direction de l'évaluation des produits réglementés Direction de l'évaluation des produits réglementés Laboratoire de la santé des végétaux Direction de l'évaluation des produits réglementés Technologies et Méthodes pour les Agricultures de demain Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement Institut Agro Montpellier Université de Montpellier

---

Résumé : L’Anses évalue les demandes d’autorisation d’introduction dans l’environnement de macro-organismes non indigènes utiles aux végétaux. Ces macro-organismes, quand ils sont utilisés dans le cadre de la lutte biologique, sont des solutions de biocontrôle.Cette mission d’évaluation repose actuellement sur deux textes réglementaires nationaux : - Le décret n° 2012-140 du 30 janvier 2012 relatif aux conditions d’autorisation d’entrée sur le territoire et d’introduction dans l’environnement de macro-organismes non indigènes utiles aux végétaux, notamment dans le cadre de la lutte biologique,- L’arrêté du 28 juin 2012 relatif aux demandes d’autorisation d’entrée sur le territoire et d’introduction dans l’environnement de macro-organismes non indigènes utiles aux végétaux, notamment dans le cadre de la lutte biologique.L’expérience acquise par l’Anses depuis l’entrée en vigueur de cette réglementation a mis en évidence la nécessité d’expliciter, via l’élaboration d’un guide, les éléments à faire figurer dans les dossiers de demande d’autorisation d’introduction dans l’environnement afin que ceux-ci soient mieux renseignés par les demandeurs. Ainsi, le guide vient préciser les requis établis à l’Annexe II de l’arrêté du 28/06/12 et propose des recommandations sur les données à fournir pour adresser ces requis dans le cadre des demandes d’autorisation et de renouvellement d’autorisation d’introduction dans l’environnement.Le développement du guide s’inscrit également, au niveau national, dans le contexte de la Stratégie Nationale de Déploiement du Biocontrôle1 publiée en novembre 2020. En particulier, l’axe 2 de ce document porte sur la simplification des procédures pour l’autorisation et l’utilisation des solutions de biocontrôle. L’établissement d’un guide par l’Anses est un livrable de l’objectif 4 intitulé « Faciliter la soumission des dossiers de demande et de renouvellement relatifs à l’utilisation des macro-organismes ».

---

Source

---

• Type de publi. : Article dans une revue
• Date de publi. : 27/10/2022
• Auteurs : Pierre BertholonLaure MazzolaMarie GavidAlexandre KarkasRoland PeyronPhilippe Convers
• Organismes : Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] Central Integration of Pain in Human Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center Service de Neurologie [CHU de Saint-Étienne] Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] Service de Neurologie [CHU de Saint-Étienne]
• Publié dans Otology and Neurotology le 02/11/2020

---

Résumé : Objectives The main objective was to describe the nystagmus observed during benign paroxysmal vertigo (BPV) of childhood, which is one of the criteria included in the three versions of the International Classification of Headache Disorders that has never been specified. The secondary objectives were to emphasize the usefulness of a mobile phone to record nystagmus and discuss the physiopathology of this nystagmus. Patient A 6-year-old boy complained of approximately 30 to 50 vertigo attacks, most of them lasting around 1 minute, during a 6-month period. Intervention Otoneurologic history and examination, audiovestibular exploration, and brain imaging were performed between the attacks. Video recording by the parents' mobile phone and video electroencephalography recording during a 1-day hospitalization were performed during the episodes. Main Outcome Measure Analysis of seven video recordings performed by the parents and four during a 1-day hospitalization, as well as follow-up. Results The assessment between the attacks confirmed the diagnosis of BPV according to International Classification of Headache Disorders criteria. Video recordings constantly demonstrated a strong left horizontal nystagmus present at fixation in all direction of gaze, enhanced in left gaze. This nystagmus was associated with a rightward body deviation. Conclusion The clinical presentation was more consistent with a peripheral vestibular deficit than with a central disorder. We encourage video recording of their child by the parents because it will help both to define the ictal nystagmus and to understand the underlying pathophysiology. The latter is discussed and is probably more complex than initially thought in BPV.

---

Source

---

• Type de publi. : Article dans une revue
• Date de publi. : 27/10/2022
• Auteurs : Omid HamidAlberto A ChiapporiJohn A ThompsonToshihiko DoiSiwen Hu-LieskovanFerry a L M EskensWilleke RosAdi DiabJean-Philippe SpanoNaiyer A RizviJeffrey S WasserEric AngevinPatrick A OttAlison ForgieWenjing YangCen GuoJeffrey ChouAnthony B El-Khoueiry
• Organismes : Epidémiologie, Systèmes d'Information, Modélisation
• Publié dans Journal for Immunotherapy of Cancer le 24/10/2020

---

Résumé : Background Ivuxolimab (PF-04518600) and utomilumab (PF-05082566) are humanized agonistic IgG2 monoclonal antibodies against OX40 and 4-1BB, respectively. This first-in-human, multicenter, open-label, phase I, dose-escalation/dose-expansion study explored safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of ivuxolimab+utomilumab in patients with advanced solid tumors. Methods Dose-escalation: patients with advanced bladder, gastric, or cervical cancer, melanoma, head and neck squamous cell carcinoma, or non-small cell lung cancer (NSCLC) who were unresponsive to available therapies, had no standard therapy available or declined standard therapy were enrolled into five dose cohorts: ivuxolimab (0.1–3 mg/kg every 2 weeks (Q2W)) intravenously plus utomilumab (20 or 100 mg every 4 weeks (Q4W)) intravenously. Dose-expansion: patients with melanoma (n=10) and NSCLC (n=20) who progressed on prior anti-programmed death receptor 1/programmed death ligand-1 and/or anti-cytotoxic T-lymphocyte-associated antigen 4 (melanoma) received ivuxolimab 30 mg Q2W intravenously plus utomilumab 20 mg Q4W intravenously. Adverse events (AEs) were graded per National Cancer Institute Common Terminology Criteria for Adverse Events V.4.03 and efficacy was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1 and immune-related RECIST (irRECIST). Paired tumor biopsies and whole blood were collected to assess pharmacodynamic effects and immunophenotyping. Whole blood samples were collected longitudinally for immunophenotyping. Results Dose-escalation: 57 patients were enrolled; 2 (3.5%) patients with melanoma (0.3 mg/kg+20 mg and 0.3 mg/kg+100 mg) achieved partial response (PR), 18 (31.6%) patients achieved stable disease (SD); the disease control rate (DCR) was 35.1% across all dose levels. Dose-expansion: 30 patients were enrolled; 1 patient with NSCLC achieved PR lasting >77 weeks. Seven of 10 patients with melanoma (70%) and 7 of 20 patients with NSCLC (35%) achieved SD: median (range) duration of SD was 18.9 (13.9–49.0) weeks for the melanoma cohort versus 24.1 (14.3–77.9+) weeks for the NSCLC cohort; DCR (NSCLC) was 40%. Grade 3–4 treatment-emergent AEs were reported in 28 (49.1%) patients versus 11 (36.7%) patients in dose-escalation and dose-expansion, respectively. There were no grade 5 AEs deemed attributable to treatment. Ivuxolimab area under the concentration–time curve increased in a dose-dependent manner at 0.3–3 mg/kg doses. Conclusions Ivuxolimab+utomilumab was found to be well tolerated and demonstrated preliminary antitumor activity in selected groups of patients. Trial registration number NCT02315066 .

---

Fichiers liés : First-in-human study of an OX40 (ivuxolimab) and 4-1BB (utomilumab) agonistic antibody combination in patients with advanced solid tumors..pdf

---

Source

---

• Type de publi. :
• Date de publi. : 26/10/2022
• Auteurs : Mikael CohenOcéane Thomel-RocchiAksel SivaDarin OkudaClarisse Carra DallièreFrançoise Durand-DubiefHélène ZéphirCéline LouapreC. BensaJonathan CironEric ThouvenotBertrand BourreOlivier CasezJérôme de SèzeThibault MoreauJean-Philippe NeauDaniel PelletierOrhun KantarciMelih TutuncuNathalie DeracheCassandre Landes-ChâteauChristine Lebrun-Frénay
• Organismes : Unité de Recherche Clinique Côte d’Azur Unité de Recherche Clinique Côte d’Azur Cerrahpasa Faculty of Medicine University of Texas Southwestern Medical Center [Dallas] Département de Neurologie [Hôpital Gui de Chauliac - CHU Montpellier] Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL] Lille Neurosciences & Cognition - U 1172 CHU Pitié-Salpêtrière [AP-HP] Service de neurologie [Hôpital Fondation Adolphe de Rothschild] Institut Toulousain des Maladies Infectieuses et Inflammatoires Centre Ressources et Compétences sclérose en plaques (CRC-SEP) [CHU Toulouse] Institut de Génomique Fonctionnelle CHU Rouen Centre Hospitalier Universitaire [CHU Grenoble] CIC Strasbourg Service de Neurologie [Strasbourg] Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon) Service de neurologie [CHU de Poitiers] University of Southern California Mayo Clinic [Rochester] Cerrahpasa Faculty of Medicine Service de Neurologie [CHU Caen] Unité de Recherche Clinique Côte d’Azur Unité de Recherche Clinique Côte d’Azur

---

Résumé : Introduction: Nowadays, mandatory vaccination in patients with multiple sclerosis (MS) is widely recommended. Regarding COVID19, the absence of specific warnings led to the proposal of vaccination in patients with inflammatory diseases of the central nervous system. However global vaccination hesitancy remains and potential effect of COVID19 vaccination on disease activity needs to be assessed. Objectives: We aimed to evaluate if COVID19 vaccination or infection increased the risk of clinical conversion to multiple sclerosis or evidence of disease activity (EDA) in a cohort of RIS subjects. Methods: This multicentric observational study is based on the RISC cohort. Data regarding COVID19 infection and vaccination has been collected between January 2020 and December 2021. We compared the occurrence of clinical conversion to MS and EDA in patients according to their vaccination status. The same analysis was conducted by comparing patients according to their history of COVID19 infection. Results: 217 subjects with known vaccination status were included (Mean age: 44yrs, F/M sex ratio 2.7). 80% of subjects had a complete vaccination and 20% were incompletely or not vaccinated. Both groups did not differ regarding the main demographical data and known risk factors of conversion to MS. No difference was found concerning clinical conversion to MS in the vaccinated versus unvaccinated group (2.4% versus 2.5%, p = 0.9747). We did not observe any statistical difference regarding the rate of EDA in both groups. 20% of subjects had a history of COVID-19 infection. The rate of clinical conversion to MS in the infected compared to the non-infected group did not show any difference The global conversion rate to MS in the whole RISC cohort in 2021 was 2.64%, which is comparable with the observed rates during the four previous years (5.75%, 2.55%, 4.79%, and 4.85% per year respectively). Conclusions: Our study suggests that COVID19 vaccination does not increase the risk of clinical conversion to MS in RIS subjects and supports that immunization can be safely proposed for these patients.

---

Source