Philippe JEAN-PIERRE

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• Type de publi. : Article dans une revue
• Date de publi. : 13/01/2023
• Auteurs : Andreas BikfalviCristine Alves da CostaTony AvrilJean-Vianney BarnierLuc BauchetLucie BrissonPierre-François CartronHélène CastelEric ChevetHerve ChneiweissAnne ClavreulBruno ConstantinValérie CoronasThomas DaubonMonique DontenwillFrançois DucrayNatacha Enz-WerleDominique Figarella-BrangerIsabelle FournierJean-Sébastien FrénelM. GabutThierry GalliJulie GavardGilles HuberfeldJean-Philippe HugnotAhmed IdbaihMarie-Pierre JunierThomas MathivetPhilippe MeneiDavid MeyronetCéline MirjoletFabrice MorinJean MosserElizabeth Cohen-Jonathan MoyalVéronique RousseauMichel SalzetMarc SansonGiorgio SeanoEmeline TabouretAurelie TchoghandjianLaurent TurchiFrançois M. ValletteSomya VatsMaïté VerreaultThierry Virolle
• Organismes : BoRdeaux Institute of onCology Institut de pharmacologie moléculaire et cellulaire Oncogenesis, Stress, Signaling CRLCC Eugène Marquis Institut des Neurosciences Paris-Saclay Institut de Génomique Fonctionnelle BoRdeaux Institute of onCology Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers Différenciation et communication neuronale et neuroendocrine Institute for Research and Innovation in Biomedicine Oncogenesis, Stress, Signaling CRLCC Eugène Marquis Neuroscience Paris Seine Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers Centre Hospitalier Universitaire d'Angers Canaux et Connexines dans les Cancers et Cellules Souches = Laboratory Channels and Connexins in Cancer and Cell Stemness [UMR 6041] Canaux et Connexines dans les Cancers et Cellules Souches = Laboratory Channels and Connexins in Cancer and Cell Stemness [UMR 6041] Institut de biochimie et génétique cellulaires Laboratoire de Bioimagerie et Pathologies Centre de Recherche en Cancérologie de Lyon Centre Léon Bérard [Lyon] Laboratoire de Bioimagerie et Pathologies Service d'Anatomo-Cyto-Pathologie et de NeuroPathologie [Hôpital de la Timone - APHM] Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 Centre Hospitalier Régional Universitaire [CHU Lille] Différenciation et communication neuronale et neuroendocrine Institute for Research and Innovation in Biomedicine Centre de Recherche en Cancérologie de Lyon Centre Léon Bérard [Lyon] Institut de psychiatrie et neurosciences de Paris Groupe hospitalier universitaire Paris psychiatrie & neurosciences [Paris] Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers Centre interdisciplinaire de recherche en biologie Institut de Génomique Fonctionnelle Institut du Cerveau = Paris Brain Institute Neuroscience Paris Seine BoRdeaux Institute of onCology Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers Centre Hospitalier Universitaire d'Angers Hospices Civils de Lyon Equipe CADIR (LNC - U1231) Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] Différenciation et communication neuronale et neuroendocrine Institute for Research and Innovation in Biomedicine Oncogenesis, Stress, Signaling CRLCC Eugène Marquis Centre de Recherches en Cancérologie de Toulouse Oncopole Claudius Regaud Institut des Neurosciences Paris-Saclay Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 Centre Hospitalier Régional Universitaire [CHU Lille] Institut du Cerveau = Paris Brain Institute CHU Charles Foix [AP-HP] Signalisation, radiobiologie et cancer Institut de neurophysiopathologie Institut de neurophysiopathologie Institut de Biologie Valrose Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers Institut de psychiatrie et neurosciences de Paris Groupe hospitalier universitaire Paris psychiatrie & neurosciences [Paris] CHU Charles Foix [AP-HP] Institut du Cerveau = Paris Brain Institute Institut de Biologie Valrose
• Publié dans Trends in Cancer le 26/10/2020

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Résumé : Glioblastoma (GBM) is the most deadly type of malignant brain tumor, despite extensive molecular analyses of GBM cells. In recent years, the tumor microenvironment (TME) has been recognized as an important player and therapeutic target in GBM. However, there is a need for a full and integrated understanding of the different cellular and molecular components involved in the GBM TME and their interactions for the development of more efficient therapies. In this review, we provide a comprehensive report of the GBM TME, which assembles the contributions of physicians and translational researchers working on brain tumor pathology and therapy in France. We propose a holistic view of the subject by delineating the specific features of the GBM TME at the cellular, molecular, and therapeutic levels.

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Fichiers liés : Challenges.pdf

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• Type de publi. : Rapport
• Date de publi. : 11/01/2023
• Auteurs : Adrien Le FrancPierre CarpentierJean-Philippe ChancelierMichel de Lara
• Organismes : Centre d'Enseignement et de Recherche en Mathématiques et Calcul Scientifique Optimisation et commande Centre d'Enseignement et de Recherche en Mathématiques et Calcul Scientifique Centre d'Enseignement et de Recherche en Mathématiques et Calcul Scientifique

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Résumé : In multistage decision problems, it is often the case that an initial strategic decision (such as investment) is followed by many operational ones (operating the investment). Such initial strategic decision can be seen as a parameter affecting a multistage decision problem. More generally, we study in this paper a standard multistage stochastic optimization problem depending on a parameter. When the parameter is fixed, Stochastic Dynamic Programming provides a way to compute the optimal value of the problem. Thus, the value function depends both on the state (as usual) and on the parameter. Our aim is to investigate on the possibility to efficiently compute gradients of the value function with respect to the parameter, when these objects exist. When nondifferentiable, we propose a regularization method based on the Moreau-Yosida envelope. We present a numerical test case from day-ahead power scheduling.

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Fichiers liés : preprint_v2_parametric.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 07/01/2023
• Auteurs : Christophe MilésiFlorent BaudinPhilippe DurandGuillaume EmeriaudSandrine EssouriRobin PouyauJulien BaleineSophie BeldjilaliAlice BordessouleSophie BreinigPierre DemaretPhilippe DesprezBénédicte Gaillard-LerouxJulie GuichouxAnne-Sophie GuilbertCamille GuillotSandrine JeanMichael LevyOdile Noizet-YverneauJérôme RambaudMorgan RecherStéphanie ReynaudFréderic VallaKarim RadouiMarie-Agnes FaureGuillaume FerraroGuillaume Mortamet
• Organismes : Centre Hospitalier Régional Universitaire [Montpellier] Hôpital Femme Mère Enfant [CHU - HCL] Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre] CHU Sainte Justine [Montréal] CHU Sainte Justine [Montréal] Hôpital Femme Mère Enfant [CHU - HCL] Centre Hospitalier Régional Universitaire [Montpellier] Hôpital de la Timone [CHU - APHM] Hôpitaux Universitaires de Genève = University Hospital of Geneva [Genève] Centre Hospitalier Universitaire de Toulouse Centre Hospitalier Universitaire de Liège CHU Pointe-à-Pitre / Abymes [Guadeloupe] Centre Hospitalier Universitaire de Nantes = Nantes University Hospital Centre Hospitalier Universitaire de Bordeaux Centre Hospitalier Universitaire [Strasbourg] Centre Hospitalier Régional Universitaire [CHU Lille] CHU Trousseau [APHP] Hôpital Robert Debré Paris Hôpital universitaire Robert Debré [Reims] CHU Trousseau [APHP] Evaluation des technologies de santé et des pratiques médicales - ULR 2694 Hôpital Femme Mère Enfant [CHU - HCL] Université de Lyon Hôpital Femme Mère Enfant [CHU - HCL] Faculté de Médecine d'Oran Hospices Civils de Lyon Centre Hospitalier Universitaire de Nice Centre Hospitalier Universitaire [CHU Grenoble]
• Publié dans Intensive Care Medicine le 27/10/2020

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Résumé : Purpose We present guidelines for the management of infants under 12 months of age with severe bronchiolitis with the aim of creating a series of pragmatic recommendations for a patient subgroup that is poorly individualized in national and international guidelines. Methods Twenty-five French-speaking experts, all members of the Groupe Francophone de Réanimation et Urgence Pédiatriques (French‐speaking group of paediatric intensive and emergency care; GFRUP) (Algeria, Belgium, Canada, France, Switzerland), collaborated from 2021 to 2022 through teleconferences and face-to-face meetings. The guidelines cover five areas: (1) criteria for admission to a pediatric critical care unit, (2) environment and monitoring, (3) feeding and hydration, (4) ventilatory support and (5) adjuvant therapies. The questions were written in the Patient-Intervention-Comparison-Outcome (PICO) format. An extensive Anglophone and Francophone literature search indexed in the MEDLINE database via PubMed, Web of Science, Cochrane and Embase was performed using pre-established keywords. The texts were analyzed and classified according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. When this method did not apply, an expert opinion was given. Each of these recommendations was voted on by all the experts according to the Delphi methodology. Results This group proposes 40 recommendations. The GRADE methodology could be applied for 17 of them (3 strong, 14 conditional) and an expert opinion was given for the remaining 23. All received strong approval during the first round of voting. Conclusion These guidelines cover the different aspects in the management of severe bronchiolitis in infants admitted to pediatric critical care units. Compared to the different ways to manage patients with severe bronchiolitis described in the literature, our original work proposes an overall less invasive approach in terms of monitoring and treatment.

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• Type de publi. : Article dans une revue
• Date de publi. : 06/01/2023
• Auteurs : Arnaud LeroyPhilippe DerambureC. HingrayW. El-HageI. WarembourgGuillaume VaivaAli Amad
• Organismes : Lille Neurosciences & Cognition - U 1172 Lille Neurosciences & Cognition - U 1172 Centre Psychothérapique de Nancy [Laxou] Centre Hospitalier Régional Universitaire de Tours Service de Psychiatrie [CHRU Lille] Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837
• Publié dans European Archives of Psychiatry and Clinical Neuroscience le 02/11/2020

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Résumé : Functional dissociative seizures (FDSs) are clinical events that resemble epileptic seizures but are not associated with abnormal brain electrical discharges or other physiological problems. In this pilot case series, ten adults with FDSs were recruited from our psychiatry department after being referred by a neurologist who made the diagnosis of FDS based on video EEG results. Each subject received ten sessions of cathodal tDCS focused on the right temporoparietal junction. A significant decrease in weekly seizure frequency was seen in all participants between baseline (30.2 ± 70.3 events) and 1 month after tDCS treatment (0.2 ± 0.3events) (p = 0.006). Main predisposing factors were unchanged after treatment.

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• Type de publi. : Article dans une revue
• Date de publi. : 05/01/2023
• Auteurs : Francois MeurensFrédéric CarlinMichel FederighiMaria-Eleni FilippitziMatthieu FournierPhilippe FravaloJean-Pierre VaillancourtJean-Pierre GanièreLionel GrisotLaurent GuillierDidier HilairePauline KoohPauline KoohSophie Le BouquinCaroline Le MaréchalChristelle MazuetChristelle MazuetHervé MorvanJean-Pierre VaillancourtCédric Woudstra
• Organismes : Biologie, Epidémiologie et analyse de risque en Santé Animale University of Saskatchewan [Saskatoon, Canada] Sécurité et Qualité des Produits d'Origine Végétale SECurité des ALIments et Microbiologie Aristotle University of Thessaloniki Morphodynamique Continentale et Côtière Université de Rouen Normandie Conservatoire National des Arts et Métiers [Cnam] Metabiot Faculté de Médecine Vétérinaire [UdeM-Saint-Hyacinthe] Retired Clinique vétérinaire des Tourbières Direction de l'Evaluation des Risques Maîtrise nucléaire, radiologique, bactériologique et chimique Direction de l'Evaluation des Risques IT University of Copenhagen Laboratoire de Ploufragan-Plouzané-Niort [ANSES] Laboratoire de Ploufragan-Plouzané-Niort [ANSES] Centre National de Référence des Bactéries Anaérobies et Botulisme - National Reference Center Anaerobic Bacteria and Botulism Direction de l'Evaluation des Risques Retired Faculté de Médecine Vétérinaire [UdeM-Saint-Hyacinthe] IT University of Copenhagen
• Publié dans Frontiers in Microbiology le 31/10/2020

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Résumé : Clostridium botulinum is the main causative agent of botulism, a neurological disease encountered in humans as well as animals. Nine types of botulinum neurotoxins (BoNTs) have been described so far. Amongst these “toxinotypes,” the A, the B and E are the most frequently encountered in humans while the C, D, C/D and D/C are mostly affecting domestic and wild birds as well as cattle. In France for instance, many cases and outbreaks are reported in these animal species every year. However, underestimation is very likely at least for avifauna species where the detection of dead animals can be challenging. Knowledge about BoNTs C, D, C/D, and D/C and the diseases they cause in animals and humans is still scarce and unclear. Specifically, the potential role of animal botulism outbreaks in cattle and poultry as a source of human illness needs to be further assessed. In this narrative review, we present the current knowledge about toxinotypes C, D, C/D, and D/C in cattle and poultry with, amongst various other aspects, their epidemiological cycles. We also discuss the zoonotic potential of these toxinotypes and some possible ways of risk mitigation. An adapted and effective management of botulism outbreaks in livestock also requires a better understanding of these less common and known toxinotypes.

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Fichiers liés : Meurens_Front Microbiol_2023.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 05/01/2023
• Auteurs : Caroline BailleuxAntoine ArnaudJean-Sébastien FrénelSylvie ChabaudThomas BachelotBenoît YouLaëtitia StefaniClaire Garnier TixidreHélène SimonDominique Beal-ArdissonJean-Philippe JacquinFrancesco del PianoAlain LortholaryClaudiu CorneaCharlotte GreilsamerRémy LargillierFabien BrocardÉric LegouffeMustapha AtlassiAnne-Claire Hardy-BessardPierre-Etienne Heudel
• Organismes : Centre Léon Bérard [Lyon]
• Publié dans Breast Cancer le 29/10/2020

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Résumé : Abstract Background The objective of the CHEOPS trial was to assess the benefit of adding aromatase inhibitor (AI) to metronomic chemotherapy, oral vinorelbine, 50 mg, three times a week for pre-treated, HR + /HER2- metastatic breast cancer patients. Methods In this multicentric phase II study, patients had to have progressed on AI and one or two lines of chemotherapy. They were randomized between oral vinorelbine (Arm A) and oral vinorelbine with non-steroidal AI (Arm B). Results 121 patients were included, 61 patients in Arm A and 60 patients in Arm B. The median age was 68 years. 109 patients had visceral metastases. They all had previously received an AI. The study had been prematurely stopped following the third death due to febrile neutropenia. Median PFS trend was found to be different with 2.3 months and 3.7 months in Arm A and Arm B, respectively (HR 0.73, 95%CI 0.50–1.06, p value = 0.0929). No statistical difference was shown in OS and better tumor response. 56 serious adverse events corresponding to 25 patients (21%) were reported (respectively, 12 (20%) versus 13 (22%) for arms A and B) (NS). Conclusion The addition of AI to oral vinorelbine over oral vinorelbine alone in aromatase inhibitor-resistant metastatic breast cancer was associated with a non-significant improvement of PFS. Several unexpected serious adverse events were reported. Metronomic oral vinorelbine schedule, at 50 mg three times a week, requires close biological monitoring. The question of hormonal treatment and chemotherapy combination remains open.

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• Type de publi. : Article dans une revue
• Date de publi. : 04/01/2023
• Auteurs : Laurene AbjeanLucile Ben HaimMiriam Riquelme-PerezPauline GipchteinCéline DerboisMarie-Ange PalomaresFanny PetitAnne-Sophie HérardMarie-Claude GaillardMartine GuillermierMylène Gaudin-GuérifGwennaëlle AuréganNisrine SagarCameron HéryNoëlle DufourNoémie RobilMehdi KabaniRonald MelkiPierre de la GrangeAlexis BemelmansGilles BonventoJean-François DeleuzePhilippe HantrayeJulien FlamentEric BonnetSolène Brohard-JulienRobert OlasoEmmanuel BrouilletM.A. Carrillo-de SauvageCarole Escartin
• Organismes : Laboratoire des Maladies Neurodégénératives - UMR 9199
• Publié dans Brain - A Journal of Neurology le 29/10/2020

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Résumé : Abstract Huntington’s disease is a fatal neurodegenerative disease characterized by striatal neurodegeneration, aggregation of mutant Huntingtin and the presence of reactive astrocytes. Astrocytes are important partners for neurons and engage in a specific reactive response in Huntington’s disease that involves morphological, molecular and functional changes. How reactive astrocytes contribute to Huntington’s disease is still an open question, especially because their reactive state is poorly reproduced in experimental mouse models. Here, we show that the JAK2-STAT3 pathway, a central cascade controlling astrocyte reactive response, is activated in the putamen of Huntington’s disease patients. Selective activation of this cascade in astrocytes through viral gene transfer reduces the number and size of mutant Huntingtin aggregates in neurons and improves neuronal defects in two complementary mouse models of Huntington’s disease. It also reduces striatal atrophy and increases glutamate levels, two central clinical outcomes measured by non-invasive magnetic resonance imaging. Moreover, astrocyte-specific transcriptomic analysis shows that activation of the JAK2-STAT3 pathway in astrocytes coordinates a transcriptional program that increases their intrinsic proteolytic capacity, through the lysosomal and ubiquitin-proteasome degradation systems. This pathway also enhances their production and exosomal release of the co-chaperone DNAJB1, which contributes to mutant Huntingtin clearance in neurons. Together, our results show that the JAK2-STAT3 pathway controls a beneficial proteostasis response in reactive astrocytes in Huntington’s disease, which involves bi-directional signalling with neurons to reduce mutant Huntingtin aggregation, eventually improving disease outcomes.

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• Type de publi. : Article dans une revue
• Date de publi. : 04/01/2023
• Auteurs : Alban CanaliInès VergnolleSarah BertoliLaetitia LargeaudMarie-Laure NicolauJean-Baptiste RieuSuzanne TavitianFrançoise HuguetMuriel PicardPierre BoriesJean-Philippe VialNicolas LechevalierMarie-Christine BénéIsabelle LuquetVéronique Mansat-de MasEric DelabesseChristian RécherFrançois Vergez
• Organismes : IUCT Oncopole IUCT Oncopole IUCT Oncopole Centre de Recherches en Cancérologie de Toulouse IUCT Oncopole Centre de Recherches en Cancérologie de Toulouse IUCT Oncopole IUCT Oncopole IUCT Oncopole IUCT Oncopole IUCT Oncopole IUCT Oncopole CHU de Bordeaux Pellegrin [Bordeaux] CHU de Bordeaux Pellegrin [Bordeaux] Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers IUCT Oncopole IUCT Oncopole Centre de Recherches en Cancérologie de Toulouse IUCT Oncopole Centre de Recherches en Cancérologie de Toulouse IUCT Oncopole Centre de Recherches en Cancérologie de Toulouse IUCT Oncopole Centre de Recherches en Cancérologie de Toulouse
• Publié dans Clinical Cancer Research le 30/10/2020

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Résumé : Purpose: Acute myeloid leukemias (AML) are clonal diseases that develop from leukemic stem cells (LSC) that carry an independent prognostic impact on the initial response to induction chemotherapy, demonstrating the clinical relevance of LSC abundance in AML. In 2018, the European LeukemiaNet published recommendations for the detection of measurable residual disease (Bulk MRD) and suggested the exploration of LSC MRD and the use of multiparametric displays. Experimental design: We evaluated the performance of unsupervised clustering for the post-induction assessment of bulk and LSC MRD in 155 patients with AML who received intensive conventional chemotherapy treatment. Results: The median overall survival (OS) for Bulk+ MRD patients was 16.7 months and was not reached for negative patients (HR, 3.82; P < 0.0001). The median OS of LSC+ MRD patients was 25.0 months and not reached for negative patients (HR, 2.84; P = 0.001). Interestingly, 1-year (y) and 3-y OS were 60% and 39% in Bulk+, 91% and 52% in Bulk-LSC+ and 92% and 88% in Bulk-LSC-. Conclusions: In this study, we confirm the prognostic impact of post-induction multiparametric flow cytometry Bulk MRD in patients with AML. Focusing on LSCs, we identified a group of patients with negative Bulk MRD but positive LSC MRD (25.8% of our cohort) with an intermediate prognosis, demonstrating the interest of MRD analysis focusing on leukemic chemoresistant subpopulations.

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• Type de publi. : Article dans une revue
• Date de publi. : 01/01/2023
• Auteurs : Anastasia DupréNathalie MorelCécile YelnikPhilippe MogueletVéronique Le GuernRomain StammlerYann NguyenRomain PauleVirginie DufrostFelix AckermannYgal BenhamouBertrand GodeauMarc LambertPierre DuffauArsène MékinianDavid SaadounLuc MouthonÉric HachullaHélène MaillardHervé LevesqueSandrine Morell-DuboisGaëlle LerouxJean-Charles PietteFrançois ChassetNathalie Costedoat-Chalumeau
• Organismes : Immunologie des Maladies Virales et Autoimmunes Infectious Diseases Models for Innovative Therapies Service de Pharmacologie et Immunoanalyse Hôpital Claude Huriez [Lille] Institute for Translational Research in Inflammation - U 1286 CHU Tenon [AP-HP] Sorbonne Université Service de médecine interne et centre de référence des maladies rares [CHU Cochin] Hôpital Cochin [AP-HP] Hôpital Beaujon [AP-HP] Hôpital Foch [Suresnes] Défaillance Cardiovasculaire Aiguë et Chronique Centre régional de compétence des Maladies systémiques et auto-immunes rares de l'adulte et Maladies vasculaires rares Hôpital Foch [Suresnes] Service de Médecine Interne [CHU Rouen] Endothélium, valvulopathies et insuffisance cardiaque Hôpital Henri Mondor Institute for Translational Research in Inflammation - U 1286 Hôpital Claude Huriez [Lille] Hôpital Saint-André Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle CHU Saint-Antoine [AP-HP] CHU Pitié-Salpêtrière [AP-HP] Hôpital Cochin [AP-HP] Institute for Translational Research in Inflammation - U 1286 Hôpital Claude Huriez [Lille] Institute for Translational Research in Inflammation - U 1286 Hôpital Claude Huriez [Lille] Endothélium, valvulopathies et insuffisance cardiaque Centre National de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest de France Institute for Translational Research in Inflammation - U 1286 Hôpital Claude Huriez [Lille] Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center CHU Pitié-Salpêtrière [AP-HP] CHU Pitié-Salpêtrière [AP-HP] CHU Tenon [AP-HP] Centre for Research in Epidemiology and Statistics | Centre de Recherche Épidémiologie et Statistiques Hôpital Cochin [AP-HP]
• Publié dans JAMA Dermatology le 28/10/2020

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Résumé : Importance Catastrophic antiphospholipid syndrome (CAPS) is a severe, rare complication of antiphospholipid syndrome (APS), but cutaneous involvement has not yet been adequately described. Objective To describe cutaneous involvement during CAPS, its clinical and pathological features, and outcomes. Design, Setting, and Participants This cohort study was a retrospective analysis of patients included in the French multicenter APS/systemic lupus erythematosus register (ClinicalTrials.gov: NCT02782039 ) by December 2020. All patients meeting the revised international classification criteria for CAPS were included, and patients with cutaneous manifestations were analyzed more specifically. Main Outcomes and Measures Clinical and pathological data as well as course and outcome in patients with cutaneous involvement during CAPS were collected and compared with those in the register without cutaneous involvement. Results Among 120 patients with at least 1 CAPS episode, the 65 (54%) with skin involvement (43 [66%] women; median [range] age, 31 [12-69] years) were analyzed. Catastrophic antiphospholipid syndrome was the first APS manifestation for 21 of 60 (35%) patients with available data. The main lesions were recent-onset or newly worsened livedo racemosa (n = 29, 45%), necrotic and/or ulcerated lesions (n = 27, 42%), subungual splinter hemorrhages (n = 19, 29%), apparent distal inflammatory edema (reddened and warm hands, feet, or face) (n = 15, 23%), and/or vascular purpura (n = 9, 14%). Sixteen biopsies performed during CAPS episodes were reviewed and showed microthrombi of dermal capillaries in 15 patients (94%). These lesions healed without sequelae in slightly more than 90% (58 of 64) of patients. Patients with cutaneous involvement showed a trend toward more frequent histologically proven CAPS (37% vs 24%, P = .16) than those without such involvement, while mortality did not differ significantly between the groups (respectively, 5% vs 9%, P = .47). Conclusions and Relevance In this cohort study, half the patients with CAPS showed cutaneous involvement, with a wide spectrum of clinical presentations, including distal inflammatory edema. Skin biopsies confirmed the diagnosis in all but 1 biopsied patient.

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• Type de publi. : Article dans une revue
• Date de publi. : 01/01/2023
• Auteurs : Paul Laffont-LozesDidier LaureillardPaul LoubetRobin StephanMyriam ChiaruzziEdouard ClemmerAurelie MartinClaire Penetrat-RogerLaurent MullerPierre-Géraud ClaretRadjiv GoulabchandClarisse RouxJean-Philippe LavigneAlbert SottoRomaric Larcher
• Organismes : Pathogenesis and Control of Chronic and Emerging Infections Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] Centre Hospitalier Régional Universitaire [Montpellier]
• Publié dans Antibiotics le 24/10/2020

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Résumé : We aimed to assess the factors associated with mortality in patients treated with tocilizumab for a SARS-CoV-2 pneumonia due to the delta or omicron variants of concern (VOC) and detect an effect of tocilizumab on mortality. We conducted a prospective cohort study in a tertiary hospital from 1 August 2021 to 31 March 2022 including patients with severe COVID-19, treated with tocilizumab. Factors associated with mortality were assessed in a Cox model; then, the 60-day mortality rates of COVID-19 patients treated with standard of care (SoC) +/− tocilizumab were compared after 1:1 propensity score matching. The mortality rate was 22% (N = 26/118) and was similar between delta and omicron cases (p = 0.6). The factors independently associated with mortality were age (HR 1.06; 95% CI (1.02–1.11), p = 0.002), Charlson index (HR 1.33; 95% CI (1.11–1.6), p = 0.002), WHO-CPS (HR 2.56; 95% CI (1.07–6.22) p = 0.03), and tocilizumab infusion within the first 48 h following hospital admission (HR 0.37, 95% CI (0.14–0.97), p = 0.04). No significant differences in mortality between the tocilizumab plus SoC and SoC alone groups (p = 0.5) were highlighted. However, the patients treated with tocilizumab within the 48 h following hospital admission had better survival (p = 0.04). In conclusion, our results suggested a protective effect on mortality of the early administration of tocilizumab in patients with severe COVID-19 regardless of the VOC involved.

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Fichiers liés : 2023 Laffont-Lozes et al., Effect of Tocilizumab.pdf

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