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659 results on '"CHU Marseille"'

101. P443 Risk of incident Cancer in Patients with Inflammatory Bowel Disease with Prior Breast Cancer: a Multicentre Cohort Study

Author: G Le Cosquer, C Gilletta, A Amiot, P Rivière, M Nachury, C Rouillon, Y Bouhnik, V Abitbol, S Nancey, M Fumery, G Savoye, A Biron, L Picon, L Peyrin-Biroulet, M Vidon, C Reenaers, M Simon, B Caron, M Serrero, R Altwegg, A Benezech, F Goutorbe, J F Rahier, L Beaugerie, A L Pelletier, L Caillo, D Laharie, F Poullenot, CHI Créteil, CHU Bordeaux [Bordeaux], Hôpital Claude Huriez [Lille], CHU Lille, CHU Clichy, Service de Gastro-entérologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Centre Hospitalier Universitaire de Nancy (CHU Nancy), Centre Hospitalier Universitaire de Liège (CHU-Liège), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Marseille, CHU Montpellier, and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Gastroenterology, General Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Breast cancer is the most common malignancy observed in patients with inflammatory bowel diseases (IBD) unrelated to the disease or its treatment (Poullenot F et al. JCC 2022). The main aim of our study was to assess the risk of incident cancer according to the IBD treatment given in patients with prior breast cancer. Methods Consecutive IBD patients with prior breast cancer diagnosis were included in a multicenter retrospective cohort from 25 tertiary centres. Inclusion date corresponded to the diagnosis of index cancer. Follow up was calculated from the first administration of immunomodulator after cancer diagnosis (or cancer diagnosis date in absence of treatment) to the occurrence of incident cancer, corresponding to recurrence of breast cancer or de novo cancer, or to the last follow-up visit. Patients were categorized according to the use or not of immunomodulator after cancer diagnosis: thiopurines, methotrexate, anti-TNF, vedolizumab, ustekinumab. Crude incidence rates were compared between patients receiving at least one immunomodulator and those without immunomodulator before and after matching on age, lymph node, and metastasis extension and tumor’s grade, using a propensity-score analysis with a 1:1 ratio. Results Among the 151 identified patients, 80 patients with full available data were analyzed: 76 (95%) women; mean age at index cancer diagnosis: 51.5 years [standard deviation (SD): 11.5 years]; 44 (55%) with Crohn’s disease, 35 (44 %) ulcerative colitis and 1 (1 %) indeterminate colitis; median IBD duration at inclusion was 13 years [interquartile range (IQR) 6-21]. After a median follow up of 84 months [IQR 49-154], 16 (20%) incident cancers were observed: 12 (15%) recurrences and 4 (5%) cancer de novo. Three (4%) patients died from cancer related cause during the follow up. 39 (49%) patients received no immunomodulator and, 11 (14%) were treated with thiopurines, 6 (7.5%) with methotrexate, 18 (22.5%) with anti-TNF, 5 (6%) with vedolizumab and one (1%) with ustekinumab. Those treatments were initiated with a median interval of 24 months [IQR 7-48] after cancer diagnosis. Crude incidence rate per 1000 person-years were 47.97 for patients not exposed to any immunomodulator and 12.61 for the others (p=0.0248). After matching, adjusted crude incidence rates per 1000 person-years were 50 and 27.27, respectively (p=0.3798). Rates of survival without incident cancer were not different between the two groups after matching on age, lymph node, metastasis extension, and tumor’s grade (p=0.17) (Figure 1). Conclusion In the present multicenter retrospective cohort, incident cancer risk among patient with IBD and prior breast cancer was not increased in patients subsequently exposed to immunomodulators.
Published: 2023

102. A Reappraisal of Outcome of Elective Surgery After Successful Non-Operative Management of an Intra-Abdominal Abscess Complicating Ileocolonic Crohn’s Disease: A Subgroup Analysis of a Nationwide Prospective Cohort

Author: R Souche, Eddy Cotte, Philippe Zerbib, Stéphane Benoist, Léon Maggiori, Jérôme Loriau, Adeline Germain, Guillaume Meurette, L Beyer-Berjot, Amine Rahili, Karine Pautrat, V Bridoux, Jean-Pierre Duffas, Yves Panis, Jérémie H. Lefevre, J. L. Faucheron, Eric Vicaut, Q Denost, M K Collard, Véronique Desfourneaux, Antoine Brouquet, H Corté, Christine Denet, Service de Chirurgie générale et digestive [CHU Le Kremlin-Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des Maladies de l'Appareil Digestif et de la Nutrition [CHRU Lille], Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Saint-André [CHU de Bordeaux], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Lyon Sud, Service de Chirurgie Digestive, Hospices Civils de Lyon (HCL), CHU Marseille, Hopital Saint-Louis [AP-HP] (AP-HP), Centre Hospitalier Universitaire de Rennes (CHU Rennes), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Toulouse [Toulouse], Service de Chirurgie d'Oncologie Digestive [CHU Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Institut Mutualiste de Montsouris (IMM), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Service de chirurgie digestive [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire [Grenoble] (CHU), Service de Chirurgie digestive [GH Paris Saint-Joseph], Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Montpellier, and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Adult, Male, medicine.medical_specialty, Abdominal Abscess, ileocolonic resection, Adolescent, Matched-Pair Analysis, Preoperative care, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, intra-abdominal abscess, Recurrence, medicine, Humans, Elective surgery, 10. No inequality, Abscess, Prospective cohort study, Aged, Aged, 80 and over, Crohn's disease, Nutritional Support, business.industry, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Intra-abdominal Abscess, General Medicine, Middle Aged, bacterial infections and mycoses, medicine.disease, Anti-Bacterial Agents, 3. Good health, Surgery, Elective Surgical Procedures, 030220 oncology & carcinogenesis, Propensity score matching, Drainage, Female, 030211 gastroenterology & hepatology, France, ileocolonic Crohn’s disease, business
Abstract: Background and AimsFew prospective data exist on outcomes of surgery in Crohn’s disease [CD] complicated by an intra-abdominal abscess after resolution of this abscess by antibiotics optionally combined with drainage.MethodsFrom 2013 to 2015, all patients undergoing elective surgery for CD after successful non-operative management of an intra-abdominal abscess [Abscess-CD group] were selected from a nationwide multicentre prospective cohort. Resolution of the abscess had to be computed tomography/magnetic resonance-proven prior to surgery. Abscess-CD group patients were 1:1 matched to uncomplicated CD [Non-Penetrating-CD group] using a propensity score. Postoperative results and long-term outcomes were compared between the two groups.ResultsAmong 592 patients included in the registry, 63 [11%] fulfilled the inclusion criteria. The abscess measured 37 ± 20 mm and was primarily managed with antibiotics combined with drainage in 14 patients and nutritional support in 45 patients. At surgery, a residual fluid collection was found in 16 patients [25%]. Systemic steroids within 3 months before surgery [p = 0.013] and the absence of preoperative enteral support [p = 0.001] were identified as the two significant risk factors for the persistence of a fluid collection. After propensity score matching, there was no significant difference between the Abscess-CD and Non-Penetrating-CD groups in the rates of primary anastomosis [84% vs 90% respectively, p = 0.283], overall [28% vs 15% respectively, p = 0.077] and severe postoperative morbidity [7% vs 7% respectively, p = 1.000]. One-year recurrence rates for endoscopic recurrence were 41% in the Abscess-CD and 51% in the Non-Penetrating-CD group [p = 0.159].ConclusionsSurgery after successful non-operative management of intra-abdominal abscess complicating CD provides good early and long-term outcomes.
Published: 2020

103. Validation of Artificial Intelligence to Support the Automatic Coding of Patient Adverse Drug Reaction Reports, Using Nationwide Pharmacovigilance Data

Author: Guillaume L, Martin, Julien, Jouganous, Romain, Savidan, Axel, Bellec, Clément, Goehrs, Mehdi, Benkebil, Ghada, Miremont, Joëlle, Micallef, Francesco, Salvo, Antoine, Pariente, Louis, Létinier, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Agence nationale de sécurité du médicament et des produits de santé [Saint-Denis] (ANSM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Assistance Publique - Hôpitaux de Marseille (APHM), Agence Nationale de Sécurité du Médicament et des Produits de Santé, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Neurosciences des Systèmes (INS), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Pharmacology, Pharmacovigilance, COVID-19 Vaccines, Drug-Related Side Effects and Adverse Reactions, Artificial Intelligence, Adverse Drug Reaction Reporting Systems, COVID-19, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pharmacology (medical), Toxicology
Abstract: International audience; INTRODUCTION: Adverse drug reaction reports are usually manually assessed by pharmacovigilance experts to detect safety signals associated with drugs. With the recent extension of reporting to patients and the emergence of mass media-related sanitary crises, adverse drug reaction reports currently frequently overwhelm pharmacovigilance networks. Artificial intelligence could help support the work of pharmacovigilance experts during such crises, by automatically coding reports, allowing them to prioritise or accelerate their manual assessment. After a previous study showing first results, we developed and compared state-of-the-art machine learning models using a larger nationwide dataset, aiming to automatically pre-code patients' adverse drug reaction reports. OBJECTIVES: We aimed to determine the best artificial intelligence model identifying adverse drug reactions and assessing seriousness in patients reports from the French national pharmacovigilance web portal. METHODS: Reports coded by 27 Pharmacovigilance Centres between March 2017 and December 2020 were selected (n = 11,633). For each report, the Portable Document Format form containing free-text information filled by the patient, and the corresponding encodings of adverse event symptoms (in Medical Dictionary for Regulatory Activities Preferred Terms) and seriousness were obtained. This encoding by experts was used as the reference to train and evaluate models, which contained input data processing and machine-learning natural language processing to learn and predict encodings. We developed and compared different approaches for data processing and classifiers. Performance was evaluated using receiver operating characteristic area under the curve (AUC), F-measure, sensitivity, specificity and positive predictive value. We used data from 26 Pharmacovigilance Centres for training and internal validation. External validation was performed using data from the remaining Pharmacovigilance Centres during the same period. RESULTS: Internal validation: for adverse drug reaction identification, Term Frequency-Inverse Document Frequency (TF-IDF) + Light Gradient Boosted Machine (LGBM) achieved an AUC of 0.97 and an F-measure of 0.80. The Cross-lingual Language Model (XLM) [transformer] obtained an AUC of 0.97 and an F-measure of 0.78. For seriousness assessment, FastText + LGBM achieved an AUC of 0.85 and an F-measure of 0.63. CamemBERT (transformer) + Light Gradient Boosted Machine obtained an AUC of 0.84 and an F-measure of 0.63. External validation for both adverse drug reaction identification and seriousness assessment tasks yielded consistent and robust results. CONCLUSIONS: Our artificial intelligence models showed promising performance to automatically code patient adverse drug reaction reports, with very similar results across approaches. Our system has been deployed by national health authorities in France since January 2021 to facilitate pharmacovigilance of COVID-19 vaccines. Further studies will be needed to validate the performance of the tool in real-life settings.
Published: 2022

104. Baseline characteristics, management, and predictors of early mortality in cardiogenic shock: insights from the FRENSHOCK registry

Author: Clement Delmas, François Roubille, Nicolas Lamblin, Laurent Bonello, Guillaume Leurent, Bruno Levy, Meyer Elbaz, Nicolas Danchin, Sebastien Champion, Pascal Lim, Francis Schneider, Alain Cariou, Hadi Khachab, Jeremy Bourenne, Marie‐France Seronde, Guillaume Schurtz, Brahim Harbaoui, Gerald Vanzetto, Charlotte Quentin, Xavier Delabranche, Nadia Aissaoui, Nicolas Combaret, Stephane Manzo‐Silberman, Danka Tomasevic, Benjamin Marchandot, Benoit Lattuca, Patrick Henry, Edouard Gerbaud, Eric Bonnefoy, Etienne Puymirat, Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Marseille, CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Maquet SAS, Daiichi-Sankyo, Fédération Française de Cardiologie, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Epidemiology, [SDV]Life Sciences [q-bio], Shock, Cardiogenic, 030204 cardiovascular system & hematology, Ventricular Function, Left, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Organ support, Humans, Diseases of the circulatory (Cardiovascular) system, 030212 general & internal medicine, Prospective Studies, Registries, Mortality, Cardiogenic shock, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Stroke Volume, Original Articles, Middle Aged, 3. Good health, RC666-701, Original Article, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Cardiology and Cardiovascular Medicine
Abstract: International audience; Aims: Published data on cardiogenic shock (CS) are scarce and are mostly focused on small registries of selected populations. The aim of this study was to examine the current CS picture and define the independent correlates of 30 day mortality in a large non-selected cohort.Methods and results: FRENSHOCK is a prospective multicentre observational survey conducted in metropolitan French intensive care units and intensive cardiac care units between April and October 2016. There were 772 patients enrolled (mean age 65.7 ± 14.9 years; 71.5% male). Of these patients, 280 (36.3%) had ischaemic CS. Organ replacement therapies (respiratory support, circulatory support or renal replacement therapy) were used in 58.3% of patients. Mortality at 30 days was 26.0% in the overall population (16.7% to 48.0% depending on the main cause and first place of admission). Multivariate analysis showed that six independent factors were associated with a higher 30 day mortality: age [per year, odds ratio (OR) 1.06, 95% confidence interval (CI): 1.04-1.08], diuretics (OR 1.74, 95% CI: 1.05-2.88), circulatory support (OR 1.92, 95% CI: 1.12-3.29), left ventricular ejection fraction
Published: 2022

105. Effect of Moderate Hypothermia vs Normothermia on 30-Day Mortality in Patients With Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation

Author: Levy, Bruno, Girerd, Nicolas, Amour, Julien, Besnier, Emmanuel, Nesseler, Nicolas, Helms, Julie, Delmas, Clément, Sonneville, Romain, Guidon, Catherine, Rozec, Bertrand, David, Helène, Bougon, David, Chaouch, Oussama, Walid, Oulehri, Hervé, Dupont, Belin, Nicolas, Gaide-Chevronnay, Lucie, Rossignol, Patrick, Kimmoun, Antoine, Duarte, Kevin, Slutsky, Arthur, Brodie, Daniel, FELLAHI, Jean-Luc, Ouattara, Alexandre, Combes, Alain, Mattei, Mathieu, Thivillier, Carine, Auchet, Thomas, Perez, Pierrre, Fritz, Caroline, Maureira, Pablo, Hubert, Maxime, Liu, Yihua, Meziani, Ferhat, Merdji, Hamid, Monnier, Alexandra, Clere-Jehl, Raphaël, Nieszkowska, Ania, Pineton, Marc, Chommeloux, Juliette, Hékimian, Guillaume, Lebreton , Guillaume, Quessard, Astrid, Imbault, Julien, Rémy, Alain, Pernot , Mathieu, Joseph, Pierre, Scollo, Giovanni, Pozzi, Matteo, Escudier, Étienne, MULLER, Michel, Dorez, Didier, Sirodot, Michel, Doguet, Fabien, Scherrer, Vincent, Aludaat, Chadi, Bernasinski, Michael, Zogheib, Elie, Caus, Thierry, Bizouarn, Philippe, Vourc’h, Mickael, Roussel, Jean-Christian, Senage, Thomas, Flecher, Erwan, Verhoye, Jean-Philippe, Roisne, Antoine, Biedermann, Sébastien, Vardon-Bounes, Fanny, Crognier, Laure, Porterie, Jean, Colson, Pascal, Gaudard, Philippe, Rouviere, Philippe, Bouadma, Lila, Sinnah, Fabrice, Nataf, Patrick, Para, Marylou, Dureau, Pauline, Djavidi, Nima, Bouglé, Adrien, Leprince, Pascal, Dessertaine, Géraldine, Durand, Michel, Albaladejo, Pierre, Martin, Cecile, Belon, François, Piton, Gael, Winiszewski, Hadrien, Perroti, Andrea, Tonon, David, Cholley, Bernard, Zlotnik, Diane, Achouh, Paul, Nougue, Hélène, Collange, Olivier, Mertes, Paul Michel, Kindo, Michel, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Réanimation Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Hôpital Privé Jacques Cartier [Massy], Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Strasbourg (UNISTRA), Hôpital Universitaire de Rangueil, Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Marseille, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Amiens-Picardie, Service de Réanimation médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes), Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], University of Toronto, Columbia University Irving Medical Center (CUIMC), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience; Importance: The optimal approach to the use of venoarterial extracorporeal membrane oxygenation (ECMO) during cardiogenic shock is uncertain.Objective: To determine whether early use of moderate hypothermia (33-34 °C) compared with strict normothermia (36-37 °C) improves mortality in patients with cardiogenic shock receiving venoarterial ECMO.Design, Setting, and Participants: Randomized clinical trial of patients (who were eligible if they had been endotracheally intubated and were receiving venoarterial ECMO for cardiogenic shock for
Published: 2022

106. Effect of Moderate Hypothermia vs Normothermia on 30-Day Mortality in Patients With Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation: A Randomized Clinical Trial

Author: Bruno, Levy, Nicolas, Girerd, Julien, Amour, Emmanuel, Besnier, Nicolas, Nesseler, Julie, Helms, Clément, Delmas, Romain, Sonneville, Catherine, Guidon, Bertrand, Rozec, Helène, David, David, Bougon, Oussama, Chaouch, Oulehri, Walid, Dupont, Hervé, Nicolas, Belin, Lucie, Gaide-Chevronnay, Patrick, Rossignol, Antoine, Kimmoun, Kevin, Duarte, Arthur S, Slutsky, Daniel, Brodie, Jean-Luc, Fellahi, Alexandre, Ouattara, Alain, Combes, Michel, Kindo, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Réanimation Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Hôpital Privé Jacques Cartier [Massy], Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Nouvel Hôpital Civil de Strasbourg, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Marseille, Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Paris 5 (UPD5), CHU Amiens-Picardie, Service de Réanimation médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire [Grenoble] (CHU), Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], University of Toronto, Columbia University [New York], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), The trial was sponsored and conducted by the Direction de la Recherche Clinique, CHU Nancy, with a grant from the French Ministry of Health., HYPO-ECMO Trial Group and the International ECMO Network (ECMONet): Mathieu Mattei MD, Carine Thivillier MD, Thomas Auchet MD, Pierrre Perez MD, Caroline Fritz MD, Pablo Maureira MD, PhD, Maxime Hubert MD, Yihua Liu MD, PhD, Ferhat Meziani MD, PhD, Hamid Merdji MD, Alexandra Monnier MD, Raphaël Clere-Jehl MD, Ania Nieszkowska MD, Marc Pineton MD, Juliette Chommeloux MD, Guillaume Hékimian MD, Guillaume Lebreton MD, Astrid Quessard MD, Julien Imbault MD, Alain Rémy MD, Mathieu Pernot MD, Pierre Joseph MD, Giovanni Scollo MD, Matteo Pozzi MD, PhD, Étienne Escudier MD, Michel Muller MD, Didier Dorez MD, Michel Sirodot MD, Fabien Doguet MD, Vincent Scherrer MD, Chadi Aludaat MD, Michael Bernasinski MD, Elie Zogheib MD, PhD, Thierry Caus MD, PhD, Philippe Bizouarn MD, PhD, Mickael Vourc'h MD, PhD, Jean-Christian Roussel MD, PhD, Thomas Senage MD, PhD, Erwan Flecher MD, PhD, Jean-Philippe Verhoye MD, PhD, Antoine Roisne MD, Sébastien Biedermann MD, Fanny Vardon-Bounes MD, PhD, Laure Crognier MD, Jean Porterie MD, Pascal Colson MD, PhD, Philippe Gaudard MD, PhD, Philippe Rouviere MD, Lila Bouadma MD, PhD, Fabrice Sinnah MD, PhD, Patrick Nataf MD, PhD, Marylou Para MD, Pauline Dureau MD, Nima Djavidi MD, Adrien Bouglé MD, PhD, Pascal Leprince MD, PhD, Géraldine Dessertaine MD, Michel Durand MD, Pierre Albaladejo MD, Cecile Martin MD, François Belon MD, Gael Piton MD, PhD, Hadrien Winiszewski MD, Andrea Perroti MD, David Tonon MD, Bernard Cholley MD, PhD, Diane Zlotnik MD, Paul Achouh MD, PhD, Hélène Nougue MD, PhD, Olivier Collange MD, PhD, Paul Michel Mertes MD, PhD, Michel Kindo MD, PhD, and Jonchère, Laurent
Subjects: Male, Time Factors, [SDV]Life Sciences [q-bio], Shock, Cardiogenic, Hemorrhage, General Medicine, Middle Aged, Respiration, Artificial, Body Temperature, [SDV] Life Sciences [q-bio], Renal Replacement Therapy, Stroke, Extracorporeal Membrane Oxygenation, Hypothermia, Induced, Sepsis, Confidence Intervals, Intubation, Intratracheal, Heart Transplantation, Humans, Female, France, Heart-Assist Devices, Erythrocyte Transfusion, Original Investigation
Abstract: ImportanceThe optimal approach to the use of venoarterial extracorporeal membrane oxygenation (ECMO) during cardiogenic shock is uncertain.ObjectiveTo determine whether early use of moderate hypothermia (33-34 °C) compared with strict normothermia (36-37 °C) improves mortality in patients with cardiogenic shock receiving venoarterial ECMO.Design, Setting, and ParticipantsRandomized clinical trial of patients (who were eligible if they had been endotracheally intubated and were receiving venoarterial ECMO for cardiogenic shock for InterventionsEarly moderate hypothermia (33-34 °C; n = 168) for 24 hours or strict normothermia (36-37 °C; n = 166).Main Outcomes and MeasuresThe primary outcome was mortality at 30 days. There were 31 secondary outcomes including mortality at days 7, 60, and 180; a composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at days 30, 60, and 180; and days without requiring a ventilator or kidney replacement therapy at days 30, 60, and 180. Adverse events included rates of severe bleeding, sepsis, and number of units of packed red blood cells transfused during venoarterial ECMO.ResultsAmong the 374 patients who were randomized, 334 completed the trial (mean age, 58 [SD, 12] years; 24% women) and were included in the primary analysis. At 30 days, 71 patients (42%) in the moderate hypothermia group had died vs 84 patients (51%) in the normothermia group (adjusted odds ratio, 0.71 [95% CI, 0.45 to 1.13], P = .15; risk difference, −8.3% [95% CI, −16.3% to −0.3%]). For the composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at day 30, the adjusted odds ratio was 0.57 (95% CI, 0.36 to 0.90; P = .02) for the moderate hypothermia group compared with the normothermia group and the risk difference was −12.7% (95% CI, −22.3% to −3.2%). Of the 31 secondary outcomes, 30 were inconclusive. The incidence of moderate or severe bleeding was 41% in the moderate hypothermia group vs 42% in the normothermia group. The incidence of infections was 52% in both groups. The incidence of bacteremia was 20% in the moderate hypothermia group vs 30% in the normothermia group.Conclusions and RelevanceIn this randomized clinical trial involving patients with refractory cardiogenic shock treated with venoarterial ECMO, early application of moderate hypothermia for 24 hours did not significantly increase survival compared with normothermia. However, because the 95% CI was wide and included a potentially important effect size, these findings should be considered inconclusive.Trial RegistrationClinicalTrials.gov Identifier: NCT02754193
Published: 2022

107. Ultra-early initiation of postoperative rehabilitation in the post-anaesthesia care unit after major thoracic surgery: case-control study

Author: Pastene, Bruno, Labarriere, Ambroise, Lopez, Alexandre, Charvet, Aude, Culver, Aurélien, Fiocchi, David, Cluzel, Armand, Brioude, Geoffrey, Einav, Sharon, Tankel, James, Hamidou, Zeinab, D’journo, Xavier Benoit, Thomas, Pascal, Leone, Marc, Zieleskiewicz, Laurent, Slim, K., Joris, J., Delaunay, L., Regimbeau, J-M., Ostermann, S., Beyer-Berjot, L., Lavand'Homme, P., Lafortune, I., Szymkiewicz, O., Venara, A., Zieleskiewicz, L., Puppo, N., Beaupère, S., Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Marseille, Aix-Marseille Université - École de médecine (AMU SMPM MED), Aix-Marseille Université - Faculté des sciences médicales et paramédicales (AMU SMPM), Aix Marseille Université (AMU)-Aix Marseille Université (AMU), Hôpital Nord [CHU - APHM], The Hebrew University of Jerusalem (HUJ), McGill University = Université McGill [Montréal, Canada], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Clermont-Ferrand, Centre Hospitalier Universitaire de Liège (CHU-Liège), Clinique Générale Annecy, CHU Amiens-Picardie, Université de Genève = University of Geneva (UNIGE), Cliniques Universitaires Saint-Luc [Bruxelles], Hospices Civils de Lyon (HCL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU d'Angers [Département Urgences], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hôpital Saint-Joseph [Marseille], UNICANCER, and Lucas, Nelly
Subjects: Pulmonary Atelectasis, Postoperative Complications, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, Case-Control Studies, Humans, Thoracic Surgery, Anesthesia, General Medicine, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Pneumonia, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: Background Physiotherapy is a major cornerstone of enhanced rehabilitation after surgery (ERAS) and reduces the development of atelectasis after thoracic surgery. By initiating physiotherapy in the post-anaesthesia care unit (PACU), the aim was to evaluate whether the ultra-early initiation of rehabilitation (in the first hour following tracheal extubation) would improve the outcomes of patients undergoing elective thoracic surgery. Methods A case–control study with a before-and-after design was conducted. From a historical control group, patients were paired at a 3:1 ratio with an intervention group. This group consisted of patients treated with the ultra-early rehabilitation programme after elective thoracic surgery (clear fluids, physiotherapy, and ambulation). The primary outcome was the incidence of postoperative atelectasis and/or pneumonia during the hospital stay. Results After pairing, 675 patients were allocated to the historical control group and 225 patients to the intervention group. A significant decrease in the incidence of postoperative atelectasis and/or pneumonia was found in the latter (11.4 versus 6.7 per cent respectively; P = 0.042) and remained significant on multivariate analysis (OR 0.53, 95 per cent c.i. 0.26 to 0.98; P = 0.045). A subgroup analysis of the intervention group showed that early ambulation during the PACU stay was associated with a further significant decrease in the incidence of postoperative atelectasis and/or pneumonia (2.2 versus 9.5 per cent; P = 0.012). Conclusions Ultra-early rehabilitation in the PACU was associated with a decrease in the incidence of postoperative atelectasis and/or pneumonia after major elective thoracic surgery.
Published: 2022

108. Sphingosine-1-Phosphate Levels Are Higher in Male Patients with Non-Classic Fabry Disease

Author: Wladimir Mauhin, Abdellah Tebani, Damien Amelin, Lenaig Abily-Donval, Foudil Lamari, Jonathan London, Claire Douillard, Bertrand Dussol, Vanessa Leguy-Seguin, Esther Noel, Agathe Masseau, Didier Lacombe, Hélène Maillard, Soumeya Bekri, Olivier Lidove, Olivier Benveniste, Médecine interne [Diaconesses Croix Saint-Simon], Groupe Hospitalier Diaconesses Croix Saint-Simon, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Marseille, Centre d'Investigation Clinique [Hôpital de la Conception - APHM] (CIC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Strasbourg, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôtel-Dieu de Nantes, CHU Bordeaux [Bordeaux], Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Lille, Hôpital Claude Huriez [Lille], Université de Lille, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Benveniste, olivier, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Fabry disease, hypertrophic cardiomyopathy, sphingosine-1-phosphate, fibrosis, migalastat, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, lipids (amino acids, peptides, and proteins), General Medicine, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: International audience; Fabry disease is an X-linked lysosomal disease in which defects in the alpha-galactosidase A enzyme activity lead to the ubiquitous accumulation of glycosphingolipids. Whereas the classic disease is characterized by neuropathic pain, progressive renal failure, white matter lesions, cerebral stroke, and hypertrophic cardiomyopathy (HCM), the non-classic phenotype, also known as cardiac variant, is almost exclusively characterized by HCM. Circulating sphingosine-1-phosphate (S1P) has controversially been associated with the Fabry cardiomyopathy. We measured serum S1P levels in 41 patients of the FFABRY cohort. S1P levels were higher in patients with a non-classic phenotype compared to those with a classic phenotype (200.3 [189.6–227.9] vs. 169.4 ng/mL [121.1–203.3], p = 0.02). In a multivariate logistic regression model, elevated S1P concentration remained statistically associated with the non-classic phenotype (OR = 1.03; p < 0.02), and elevated lysoGb3 concentration with the classic phenotype (OR = 0.95; p < 0.03). S1P levels were correlated with interventricular septum thickness (r = 0.46; p = 0.02). In a logistic regression model including S1P serum levels, phenotype, and age, age remained the only variable significantly associated with the risk of HCM (OR = 1.25; p = 0.001). S1P alone was not associated with cardiac hypertrophy but with the cardiac variant. The significantly higher S1P levels in patients with the cardiac variant compared to those with classic Fabry suggest the involvement of distinct pathophysiological pathways in the two phenotypes. S1P dosage could allow the personalization of patient management.
Published: 2022

109. Safety and efficacy of riluzole in spinocerebellar ataxia type 2 in France (ATRIL): a multicentre, randomised, double-blind, placebo-controlled trial

Author: Giulia Coarelli, Anna Heinzmann, Claire Ewenczyk, Clara Fischer, Marie Chupin, Marie-Lorraine Monin, Hortense Hurmic, Fabienne Calvas, Patrick Calvas, Cyril Goizet, Stéphane Thobois, Mathieu Anheim, Karine Nguyen, David Devos, Christophe Verny, Vito A G Ricigliano, Jean-François Mangin, Alexis Brice, Sophie Tezenas du Montcel, Alexandra Durr, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Building large instruments for neuroimaging: from population imaging to ultra-high magnetic fields (BAOBAB), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (ISC-MJ), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Hôpital de Hautepierre [Strasbourg], Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Marseille, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (CNC), and Coarelli, Giulia
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], Neurology (clinical)
Abstract: International audience; BackgroundRiluzole has been reported to be beneficial in patients with cerebellar ataxia; however, effectiveness in individual subtypes of disease is unclear due to heterogeneity in participants' causes and stages of disease. Our aim was to test riluzole in a single genetic disease, spinocerebellar ataxia type 2.MethodsWe did a randomised, double-blind, placebo-controlled, multicentre trial (the ATRIL study) at eight national reference centres for rare diseases in France that were part of the Neurogene National Reference Centre for Rare Diseases. Participants were patients with spinocerebellar ataxia type 2 with an age at disease onset of up to 50 years and a scale for the assessment and rating of ataxia (SARA) score of at least 5 and up to 26. Patients were randomly assigned centrally (1:1) to receive either riluzole 50 mg orally or placebo twice per day for 12 months. Two visits, at baseline and at 12 months, included clinical measures and 3T brain MRI. The primary endpoint was the proportion of patients whose SARA score improved by at least 1 point. Analyses were done in the intention-to-treat population (all participants who were randomly assigned) and were done with only the observed data (complete case analysis). This trial is registered at ClinicalTrials.gov (NCT03347344) and has been completed.FindingsBetween Jan 18, 2018, and June 14, 2019, we enrolled 45 patients. 22 patients were randomly assigned to receive riluzole and 23 to receive placebo. Median age was 42 years (IQR 36–57) in the riluzole group and 49 years (40–56) in the placebo group and 23 (51%) participants were women. All participants presented with moderate-stage disease, characterised by a median SARA score of 13·5 (IQR 9·5–16·5). The primary endpoint, SARA score improvement of at least 1 point after 12 months, was observed in seven patients (32%) in the treated group versus nine patients (39%) in the placebo group, with a mean difference of −10·3% (95% CI −37·4% to 19·2%; p=0·75). SARA score showed a median increase (ie, worsening) of 0·5 points (IQR −1·5 to 1·5) in the riluzole group versus 0·3 points (−1·0 to 2·5) in the placebo group (p=0·70). No serious adverse event was reported in the riluzole-treated group whereas four patients in placebo group had a serious adverse event (hepatic enzyme increase, fracture of external malleolus, rectorrhagia, and depression). The number of patients with adverse events was similar in both groups (riluzole 16 [73%] patients vs placebo 19 [83%] patients; p=0·49).InterpretationWe were able to recruit 45 patients moderately affected by spinocerebellar ataxia type 2 for this trial. Riluzole did not improve clinical or radiological outcomes in these patients. However, our findings provide data on progression of spinocerebellar ataxia type 2 that might prove to be valuable for the design of other clinical trials.
Published: 2022

110. ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition

Author: Oussama Abla, Stephen Peeke, Irem Eldem, Marianne D. van de Wetering, Jennifer Picarsic, Kseniya Petrova-Drus, Robert B. Lorsbach, Jan A M van Laar, Paul Geraeds Kemps, Sylvie Fraitag, Sébastien Héritier, Kristian T. Schafernak, Amy A. Swanson, Eli L. Diamond, Raf Sciot, Karen Ernestus, Mariko Suchi, Nabeel R. Yaseen, Sanda Alexandrescu, Laura Sophia Hiemcke-Jiwa, Matthew Collin, Ingrid S Tam, Sabrina Rossi, Benjamin H. Durham, F J Sherida H Woei-A-Jin, James A. Whitlock, Brianna Empringham, Laura Munoz-Arcos, Falko Fend, Olga Gryniewicz-Kwiatkowska, Majid Madni, Verena Wiegering, Kerry Turner, Dina El Demellawy, Gianpiero Tamburrini, Aditya Raghunathan, Lucas R. Massoth, Carel J. M. van Noesel, Robert Möhle, Cor van den Bos, Jacinthe Bonneau-Lagacherie, Somak Roy, Pasquale M Barbaro, Andreas Beilken, Stefania Gaspari, Jean-François Emile, David D. Grier, Claire Lamaison, Kee Kiat Yeo, Jean Donadieu, Jon M Brandt, Laure Farnault, Friedrich Feuerhake, Marie-Laure Jullie, Uta Flucke, Pancras C.W. Hogendoorn, Astrid G. S. van Halteren, Antje Bornemann, Bryan A. Sisk, Tina Méry, Joanna Weinstein, Ashish R Kumar, Robert M. Verdijk, V. Baykov, Alysa A Poulin, Mandy M Atkinson, VG Potapenko, Vaish Sridhar, Julien Haroche, Zofia Hélias-Rodzewicz, Shipra Garg, Susan Picton, Michael M. Henry, Jackie Allotey, Daniel Leino, Nishant Tiwari, Martin Ebinger, Jason L Hornick, Bożenna Dembowska-Bagińska, Marco Gessi, Dmitry A Evseev, Paediatric Oncology, CCA - Cancer biology and immunology, Pathology, CCA - Cancer Treatment and Quality of Life, Leiden University Medical Center (LUMC), Universiteit Leiden, Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Ambroise Paré [AP-HP], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pontchaillou [Rennes], CHU Marseille, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], CHU Pitié-Salpêtrière [AP-HP], National Institutes of Health, NIH, National Cancer Institute, NCI: P30 CA008748, R37 CA259260-01, Cincinnati Children's Hospital Medical Center, University of Saskatchewan, Leids Universitair Medisch Centrum, LUMC, Institut National Du Cancer, INCa: PRT-K19-143, P.G.K. received a grant from Leiden University Medical Center. A.G.S.v.H. is supported by Stichting 1000 kaarsjes voor Juultje. E.L.D. is supported by the National Institutes of Health/National Cancer Institute Core Grant (P30 CA008748), National Cancer Institute (R37 CA259260-01), the Frame Fund, Applebaum Foundation, and Joy Family West Foundation. J.-F.E. is supported by the Programme de Recherche Translationnelle sur le Cancer from the French National Cancer Institute (PRT-K19-143)., and The authors acknowledge the International Rare Histiocytic Disorders Registry (IRHDR, ClinicalTrial.gov number NCT02285582), which included some patients described in this study. The authors thank Chris Woods (Lead Analyst, Imaging Informatics) and the Research Pathology Laboratory at Cincinnati Children's Hospital Medical Center, John DeCoteau (molecular pathologist) at University of Saskatchewan, Sven van Kempen (senior laboratory technician) and Lennart Kester (clinical molecular biologist in pathology in training) at Princess M?xima Center for Pediatric Oncology, and Demi van Egmond (laboratory technician), Tom van Wezel (clinical molecular biologist in pathology), and Arjen Cleven (pathologist) at Leiden University Medical Center for technical assistance. The authors thank Els Wauters (pulmonologist and respiratory oncologist) at University Hospitals Leuven, Andreas Rosenwald (pathologist) at the Institute of Pathology of the University of W?rzburg, and Bipin Mathew (pathologist) at Leeds Teaching Hospitals for clinical care and/or diagnostics of patients described in this study. The authors thank Les Laboratoires Servier for allowing the use of their medical illustrations (Servier Medical Art, https://smart.servier.com) in the visual abstract. Figure 6 was created with BioRender.com. P.G.K. received a grant from Leiden University Medical Center. A.G.S.v.H. is supported by Stichting 1000 kaarsjes voor Juultje. E.L.D. is supported by the National Institutes of Health/National Cancer Institute Core Grant (P30 CA008748), National Cancer Institute (R37 CA259260-01), the Frame Fund, Applebaum Foundation, and Joy Family West Foundation. J.-F.E. is supported by the Programme de Recherche Translationnelle sur le Cancer from the French National Cancer Institute (PRT-K19-143).
Subjects: Adult, Histiocytic Disorders, Malignant, Male, Pathology, medicine.medical_specialty, Adolescent, Oncogene Proteins, Fusion, [SDV]Life Sciences [q-bio], BLOOD COMMENTARY, Immunology, Disease, Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9], Biochemistry, Young Adult, hemic and lymphatic diseases, medicine, Humans, Anaplastic Lymphoma Kinase, Child, Protein Kinase Inhibitors, Histiocyte, Retrospective Studies, business.industry, Infant, Histology, Cell Biology, Hematology, medicine.disease, Phenotype, Histiocytosis, Histiocytic neoplasm, Child, Preschool, Female, Nervous System Diseases, business
Abstract: Contains fulltext : 249882.pdf (Publisher’s version ) (Closed access) ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3 infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (7 and 12 from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one-third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated extracellular signal-regulated kinase, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, whereas CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK, and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, 10 with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis and provides guidance for the clinical management of this emerging histiocytic entity.
Published: 2022

111. Effectiveness and safety of dupilumab in the treatment of atopic dermatitis in children (6-11 years): data from a French multicentre retrospective cohort in daily practice

Author: Lasek, A., Bellon, N., Mallet, S., Puzenat, E., Bursztejn, A.C., Abasq, C., Mazereeuw‐hautier, J, Chiaverini, C., Hubiche, T., Raison Peyron, N., Du Thanh, A., Barbarot, Sébastien, Aubert, H., Reguiai, Z., Droitcourt, C., Fievet, C., Bellissen, A., Bachelerie, M., Nosbaum, A., Leymarie, A., Armingaud, P., Masson Regnault, M., Mahé, E., Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Dermatologie et Allergologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Archet 2 [Nice] (CHU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiopathologie des Adaptations Nutritionnelles (PhAN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Lille, CHU Marseille, CHU Clermont-Ferrand, Université de Lyon, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Régional d'Orléans (CHRO), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Victor Dupouy, and None
Subjects: atopic dermatitis, Dermatology, Conjunctivitis, Severity of Illness Index, Dermatitis, Atopic, Immunoglobulin A, Cohort Studies, Infectious Diseases, Treatment Outcome, children, dupilumab, Humans, daily practice, Child, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Retrospective Studies
Abstract: International audience; Background: Dupilumab is the first biotherapy available for the treatment of moderate-to-severe childhood atopic dermatitis (AD).Objective: The aim of this study was to evaluate the effectiveness and safety of dupilumab in daily practice.Methods: Patients aged 6-11, who had received a first dose of dupilumab, were included in this multicentre retrospective cohort study. The primary endpoint was change in SCORAD after 3 months of treatment. Secondary endpoints were change in IGA score at 3 months, proportion of patients with SCORAD50 and SCORAD75, description of adverse events and proportion of children in our cohort who would be excluded from pivotal phase 3 clinical trial.Results: Eighty patients were included. After 3 months of treatment, there was a significant decrease in SCORAD (mean: 21.8 ± 13.8 vs 53.9 ± 18.5; P < 0.0001) and IGA (1.3 ± 0.8 vs 3.5 ± 0.7; P < 0.0001). Conjunctivitis was observed in 11.3% (n = 9/80); three patients experienced dupilumab facial redness (DFR); 17.5% (n = 14/80) reported injection site reactions; 6.3% (n = 5/80) discontinued treatment. 61.2% (n = 49/80) children were ineligible in the phase 3 trial.Limitations: There is no control group. Because it was a real life study based on information from patient medical records in a French multicentre cohort, we cannot rule out the presence of reporting bias generated by the use of patient reported characteristics and missing information.Conclusion: These real-life data confirm the efficacy and safety of dupilumab in children with moderate to severe AD extended to dyshidrosis and atopic prurigo, but it also revealed a lower frequency of DFR and conjunctivitis. However, administration in injectable form may be a barrier in this age group.
Published: 2022

112. Recommandations de pratique pour le diagnostic et la prise en charge de la rectocolite hémorragique

Author: Amiot, A., Viennot, S., Uzzan, M., Riviere, P., Cosquer, G.L., Yzet, C., Biron, A, Gilletta, C., Abitbol, V., Vuitton, L., Nachury, M., Simon, M., Remy, A.-J., Nahon, S., Faure, P., Guillo, L., Wils, P., Brixi, H., Bourrier, A., Serrero, M., Caillo, L., Bouguen, G., Laharie, D, Hôpital Bicêtre, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Henri Mondor, CHU Bordeaux [Bordeaux], CHU Amiens-Picardie, Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Mutualiste de Montsouris (IMM), Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, Clinique Ambroise Paré [Centres Médico-Chirurgicaux Ambroise Pré, Pierre Cherest, Hartmann], CHU Marseille, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and CHU Pontchaillou [Rennes]
Subjects: [SDV]Life Sciences [q-bio], Inflammatory Bowel Disease, diagnostic, guidelines, ulcerative colites, traitement
Abstract: National audience; Background: Updating French clinical guidelines for diagnostic and management of ulcerative colitis is needed due to the emergence of new treatments and treatment goals. Methods: On behalf of the Groupe d'Etudes Therapeutiques des Affections Inflammatoires du Tube Digestif (GETAID), French clinical guidelines were updated through a validated process of adaptation of clinical guidelines from international Gastroenterology societies and French consensus meetings. Results: French clinical guidelines for the diagnostic and management of ulcerative colitis were drafted by 16 GETAID members and reviewed by 6 members of the GETAID, the Association Nationale des Hépato-gastroentérologues des Hôpitaux généraux (ANGH) and the Club de Réflexion des Cabinets et Groupes d'Hépato-Gastroentérologie (CREGG), graded according to the level of Evidence and the level of agreement by 68 experts from the latter three societies. The present guidelines focused on classification, diagnosis, histopathology, extra-intestinal manifestations, dysplasia and colorectal cancer, pouchitis, medical management of active disease and maintenance therapy.. Conclusion: This paper provides updated and useful guidelines for French gastroenterologists to diagnose and treat patients with ulcerative colitis. © John Libbey Eurotext, 2022.
Published: 2022

113. Altered epithelial barrier functions in the colon of patients with spina bifida

Author: Charlène Brochard, Guillaume Bouguen, Raphael Olivier, Tony Durand, Sébastien Henno, Benoît Peyronnet, Mael Pagenault, Chloé Lefèvre, Gaëlle Boudry, Mikael Croyal, Alain Fautrel, Maxime Esvan, Alain Ropert, Anne Dariel, Laurent Siproudhis, Michel Neunlist, CHU Pontchaillou [Rennes], The Enteric Nervous System in gut and brain disorders [U1235] (TENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre référence maladies rares Spina Bifida, Service des Maladies de l'Appareil Digestif [CHU Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service d'anatomopathologie [Rennes], Hôpital Pontchaillou, Service d'urologie [Rennes] = Urology [Rennes], Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Mass Spectrometry Core Facility [Nantes] (CRNH-O ), Structure fédérative de recherche François Bonamy (Nantes Univ - SFR François Bonamy), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université (Nantes Univ), H2P2 - Histo Pathologie Hight Precision (H2P2), Université de Rennes (UR)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Marseille, and Bernard, Emilie
Subjects: Adult, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Colon, Rectum, Colonoscopy, Coleoptera, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Surveys and Questionnaires, Animals, Humans, Spinal Dysraphism, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Our objectives were to better characterize the colorectal function of patients with Spina Bifida (SB). Patients with SB and healthy volunteers (HVs) completed prospectively a standardized questionnaire, clinical evaluation, rectal barostat, colonoscopy with biopsies and faecal collection. The data from 36 adults with SB (age: 38.8 [34.1–47.2]) were compared with those of 16 HVs (age: 39.0 [31.0–46.5]). Compared to HVs, rectal compliance was lower in patients with SB (p = 0.01), whereas rectal tone was higher (p = 0.0015). Ex vivo paracellular permeability was increased in patients with SB (p = 0.0008) and inversely correlated with rectal compliance (r = − 0.563, p = 0.002). The expression of key tight junction proteins and inflammatory markers was comparable between SB and HVs, except for an increase in Claudin-1 immunoreactivity (p = 0.04) in SB compared to HVs. TGFβ1 and GDNF mRNAs were expressed at higher levels in patients with SB (p = 0.02 and p = 0.008). The levels of acetate, propionate and butyrate in faecal samples were reduced (p = 0.04, p = 0.01, and p = 0.02, respectively). Our findings provide evidence that anorectal and epithelial functions are altered in patients with SB. The alterations in these key functions might represent new therapeutic targets, in particular using microbiota-derived approaches.Clinical Trials: NCT02440984 and NCT03054415.
Published: 2022

114. Nutritional status at age 1 year in patients born with esophageal atresia: A population-based, prospective cohort study

Author: Depoortere, S. (Suzanne), Lapillonne, A. (Alexandre), Sfeir, R. (Rony), Bonnard, A. (Arnaud), Gelas, T. (Thomas), Panait, N. (Nicoleta), Rabattu, P-Y. (Pierre-Yves), Guignot, A. (Audrey), Lamireau, T. (Thierry), Irtan, S. (Sabine), Habonimana, E. (Edouard), Breton, A. (Anne), Fouquet, V. (Virginie), Allal, H. (Hossein), Elbaz, F. (Frédéric), Talon, I. (Isabelle), Ranke, A. (Aline), Abely, M. (Michel), Michel, J-L. (Jean-Luc), Lirussi Borgnon, J. (Joséphine), Buisson, P. (Philippe), Schmitt, F. (Françoise), Lardy, H. (Hubert), Petit, T. (Thierry), Chaussy, Y. (Yann), Borderon, C. (Corinne), Levard, G. (Guillaume), Cremillieux, C. (Clara), Tolg, C. (Cécilia), Breaud, J. (Jean), Jaby, O. (Olivier), Grossos, C. (Céline), De Vries, P. (Philine), Arnould, M. (Myriam), Pelatan, C. (Cécile), Geiss, S. (Stephan), Laplace, C. (Christophe), Kyheng, M. (MaÉva), Nicolas, A. (Audrey), Aumar, M. (Madeleine), gottrand, F. (Fréderic), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Lille, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP Hôpital universitaire Robert-Debré [Paris], Hospices Civils de Lyon (HCL), CHU Marseille, CHU Grenoble, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Bordeaux [Bordeaux], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Bicêtre, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Rouen, Normandie Université (NU), CHU Strasbourg, ESPRI-Biobase [CHRU Nancy] (Unité fonctionnelle de la plateforme d’aide à la recherche clinique), CHR La réunion, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Amiens-Picardie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Clermont-Ferrand, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Saint-Etienne, CHU de la Martinique [Fort de France], Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Henri Mondor, CHU Limoges, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Le Mans (CH Le Mans), CH Colmar, CHU Pointe-à-Pitre/Abymes [Guadeloupe], BOURGEAIS, Véronique, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Henri Mondor [Créteil], Université de Lille, Inserm, Institute for Translational Research in Inflammation - U 1286 [INFINITE (Ex-Liric)], Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], and Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Subjects: catch-up, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV]Life Sciences [q-bio], growth, prematurity, stunting, syndromic, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV] Life Sciences [q-bio], undernutrition, small for gestational age, Pediatrics, Perinatology and Child Health, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: ObjectiveDespite recent progress in caring for patients born with esophageal atresia (EA), undernutrition and stunting remain common. Our study objective was to assess nutritional status in the first year after birth with EA and to identify factors associated with growth failure.Study designWe conducted a population-based study of all infants born in France with EA between 2010 and 2016. Through the national EA register, we collected prenatal to 1 year follow-up data. We used body mass index and length-for-age ratio Z scores to define patients who were undernourished and stunted, respectively. Factors with P < 0.20 in univariate analyses were retained in a logistic regression model.ResultsAmong 1,154 patients born with EA, body mass index and length-for-age ratio Z scores at 1 year were available for about 61%. Among these, 15.2% were undernourished and 19% were stunted at the age of 1 year. There was no significant catch-up between ages 6 months and 1 year. Patients born preterm (41%), small for gestational age (17%), or with associated abnormalities (55%) were at higher risk of undernutrition and stunting at age 1 year (P < 0.05). Neither EA type nor surgical treatment was associated with growth failure.ConclusionUndernutrition and stunting are common during the first year after birth in patients born with EA. These outcomes are significantly influenced by early factors, regardless of EA type or surgical management. Identifying high-risk patient groups with EA (i.e., those born preterm, small for gestational age, and/or with associated abnormalities) may guide early nutritional support strategies.
Published: 2022

115. How PET-CT is Changing the Management of Non-metastatic Castration-resistant Prostate Cancer?

Author: M. Baboudjian, M. Gauthé, E. Barret, L. Brureau, P. Rocchi, G. Créhange, C. Dariane, G. Fiard, G. Fromont, J.-B. Beauval, R. Mathieu, R. Renard-Penna, G. Roubaud, A. Ruffion, P. Sargos, M. Rouprêt, G. Ploussard, CHU Marseille, Centre Européen de Recherche en Imagerie médicale (CERIMED), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-École Centrale de Marseille (ECM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Centre National de la Recherche Scientifique (CNRS), Universitat Autònoma de Barcelona (UAB), Institut Mutualiste de Montsouris (IMM), CHU Pointe-à-Pitre/Abymes [Guadeloupe], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Curie [Paris], Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Clinique La Croix du Sud, CHU Pontchaillou [Rennes], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Bergonié [Bordeaux], UNICANCER, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre pour l'innovation en cancérologie de Lyon (CICLY), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and BAYER
Subjects: Prostate cancer, PET, Urology, PSMA, Non-metastatic, [SDV.CAN]Life Sciences [q-bio]/Cancer, Castration-resistant
Abstract: International audience; Introduction: The aim of this narrative review conducted by the Prostate Cancer Committee of the French Association of Urology (CC-AFU) was to provide an update on the current evidence for the impact of PET/CT in the management of men with non-metastatic castration-resistant prostate cancer (nmCRPC). Material and methods: This review is based on data available in the literature on PET/CT imaging for staging nmCRPC patients. A PubMed search and narrative review of the data were performed in March 2022. Only articles in French or English were considered. Results: Current guidelines recommend bone scan and CT scan as standard imaging modalities for staging and follow-up of patients with nmCRPC. Nearly one-third of asymptomatic patients with presumed nmCRPC ultimately have metastatic disease on conventional imaging. Increasing reports have shown that conventional imaging has limited accuracy in detecting metastatic disease in nmCRPC patients, leading to the development of next-generation imaging techniques. In a retrospective study, F-18-choline PET/CT detected distant metastases in 27/58 high-risk nmCRPC patients with prior negative conventional imaging. The implementation of radiolabeled ligands of the prostate-speci c membrane antigen (PSMA) PET/CT in staging strategy has resulted in metastasis detection in 45% to 98% of patients with presumptive nmCRPC on conventional imaging. Such an early diagnosis of metastatic CRPC may allow patients to be referred for metastasis-directed therapies (i.e. stereotactic body radiotherapy), aimed at prolonging the ef cacy of systemic therapies and improving clinical outcomes. However, current data are not strong enough to recommend this strategy, which must be properly evaluated in clinical trials. Indeed, the use of molecular imaging may lead to inappropriate undertreatment if the secondgeneration androgen receptor inhibitors (darolutamide, enzalutamide, apalutamide), which prolong life, are not used in the subgroup of patients with high PSA velocity (PSA doubling time
Published: 2022

116. Recommandations du comité de cancérologie de l'Association Française d'Urologie - actualisation 2022-2024: prise en charge du cancer du rein

Author: Bigot, Pierre, Barthelemy, Philippe, Boissier, Romain, Khene, Ze E., Pettenati, Caroline, Bernhard, Jean Christophe, Correas, Jean Michel, Doumerc, Nicolas, Gimel, Pierre, Ingels, Alexandre, Nouhaud, François Xavier, Ouzaïd, Idir, Rioux-Leclercq, Nathalie C., Albiges, Laurence, Rouprêt, Morgan, Institut de Cancérologie de Strasbourg Europe (ICANS), Aix Marseille Université (AMU), CHU Marseille, CHU Pontchaillou [Rennes], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Foch [Suresnes], Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de radiologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Groupe Urologie Medipole, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Rouen, Normandie Université (NU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Institut Gustave Roussy (IGR), Université Paris-Saclay, Département de médecine oncologique [Gustave Roussy], CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Tyrosine kinase inhibitors, Renal cancer, French, [SDV]Life Sciences [q-bio], Immunotherapy, Recommendation, Nephrectomy
Abstract: International audience; Aim: To update the recommendations for the management of kidney cancers. Methods: A systematic review of the literature was conducted from 2015 to 2022. The most relevant articles on the diagnosis, classification, surgical treatment, medical treatment and follow-up of kidney cancer were selected and incorporated into the recommendations. Therefore, the recommendations were updated while specifying the level of evidence (high or low). Results: The gold standard for the diagnosis and evaluation of kidney cancer is contrast-enhanced chest and abdominal CT. MRI and contrast-enhanced ultrasound are indicated in special cases. Percutaneous biopsy is recommended in situations where the results will influence the therapeutic decision. Renal tumours should be classified according to the pTNM 2017 classification, the WHO 2022 classification and the ISUP nucleolar grade. Metastatic kidney cancer should be classified according to the IMDC criteria. Partial nephrectomy is the gold standard treatment for T1a tumours and can be performed by an open approach, by laparoscopy or by robot-guidance. Active surveillance of tumours less than 2 cm in size can be considered regardless of the patient's age. Ablative therapies and active surveillance are options in elderly patients with comorbidity. T1b tumours should be treated by partial or radical nephrectomy depending on the complexity of the tumour. Radical nephrectomy is the first-line treatment for locally advanced cancers. Adjuvant treatment with pembrolizumab should be considered in patients at intermediate and high risk for recurrence after nephrectomy. In metastatic patients: Immediate cytoreductive nephrectomy may be offered to oligometastatic patients in combination with local treatment of metastases if this can be complete and delayed cytoreductive nephrectomy can be proposed for patients with a complete response or a significant partial response. Medical treatment should be proposed as first-line therapy for patients with a poor or intermediate prognosis. Surgical or local treatment of metastases can be proposed in case of single or oligo-metastases. The recommended first-line drugs for metastatic patients with clear cell renal carcinoma are the combinations axitinib/pembrolizumab, nivolumab/ipililumab, nivolumab/cabozantinib and lenvatinib/pembrolizumab. Cabozantinib is the recommended first-line treatment for patients with metastatic papillary carcinoma. Cystic tumours should be classified according to the Bosniak classification. Surgical removal should be proposed as a priority for Bosniak III and IV lesions. It is recommended that patient monitoring be adapted to the aggressiveness of the tumour. Conclusion: These updated recommendations are a reference that will allow French and French-speaking practitioners to improve kidney cancer management.
Published: 2022

117. Mortality and cardiac resynchronization therapy with or without defibrillation in primary prevention

Author: Deharo, Pierre, Bisson, Arnaud, Herbert, Julien, Lacour, Thibaud, Saint Etienne, Christophe, Jaussaud, Nicolas, Theron, Alexis, Collart, Frederic, Bourguignon, Thierry, Cuisset, Thomas, Fauchier, Laurent, Gras, Matthieu, Bodin, Alexandre, Babuty, Dominique, Pierre, Bertrand, Clementy, Nicolas, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Éducation Éthique Santé EA 7505 (EES), Université de Tours (UT), CHU Marseille, Hôpital de la Timone [CHU - APHM] (TIMONE), Département de Cardiologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and EA4245 - Transplantation, Immunologie, Inflammation [Tours] (T2i)
Subjects: medicine.medical_specialty, medicine.medical_treatment, Myocardial Ischemia, Cardiomyopathy, Cardiac resynchronization therapy, [SHS]Humanities and Social Sciences, Cardiac Resynchronization Therapy, Risk Factors, Physiology (medical), Internal medicine, medicine, Humans, Cardiac Resynchronization Therapy Devices, Aged, Heart Failure, business.industry, Mortality rate, Hazard ratio, Implantable cardioverter-defibrillator, medicine.disease, Confidence interval, Defibrillators, Implantable, Primary Prevention, Death, Sudden, Cardiac, Treatment Outcome, Heart failure, Population study, Cardiology and Cardiovascular Medicine, business
Abstract: Aims Cardiac resynchronization therapy with (CRTD) or without (CRTP) defibrillator is recommended in selected patient with systolic chronic heart failure and wide QRS. There is no guideline firmly indicating choice between CRTP and CRTD in primary prevention, particularly in older patients. Methods and results Based on the French administrative hospital-discharge database, information was collected from 2010 to 2017 for all patients implanted with CRTP or CRTD in primary prevention. Outcome analyses were undertaken in the total study population and in propensity-matched samples. During follow-up (913 days, SD 841, median 701, IQR 151–1493), 45 697 patients were analysed (CRTP 19 266 and CRTD 26 431). Incidence rate (%patient/year) of all-cause mortality was higher in CRTP patients (11.6%) than in CRTD patients (6.8%) [hazard ratio (HR) 1.70, 95% confidence interval (CI) 1.63–1.76, P Conclusion In this real-life study, CRTD was associated with a significantly lower all-cause mortality than CRTP in patients with ICM and in patients with NICM under 75 years old. Patients over 75 years old with NICM did not have lower mortality with primary prevention CRTD implantation.
Published: 2020

118. Post-vaccine COVID-19 in patients with multiple sclerosis or neuromyelitis optica

Author: Edouard Januel, Jérôme De Seze, Patrick Vermersch, Elisabeth Maillart, Bertrand Bourre, Julie Pique, Xavier Moisset, Caroline Bensa, Adil Maarouf, Jean Pelletier, Sandra Vukusic, Bertrand Audoin, Céline Louapre, Stéphane Beltran, Eric Berger, Kevin Bigaut, Nathalie Derache, Salimata Gassama, Olivier Heinzlef, Laurent Kremer, Philippe Kerschen, Aude Maurousset, Vito A G Ricigliano, Pierre-Yves Garcia, Pierre Labauge, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, CHU Lille, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (MIRCEM), Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Service de Neurologie [CHU Nice], Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), CHU Marseille, Département de Neuroradiologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Service de Neurologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), CHI Poissy-Saint-Germain, Excitabilité nerveuse et thérapeutique (ENT), Hôpital Henri Mondor-EA 4391, Service de Physiologie Explorations Fonctionnelles-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Gestionnaire, HAL Sorbonne Université 5
Subjects: Multiple Sclerosis, Neurology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Fingolimod Hydrochloride, SARS-CoV-2, Neuromyelitis Optica, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, COVID-19, Humans, Neurology (clinical), BNT162 Vaccine
Abstract: Introduction: Recent studies suggested that anti-CD20 and fingolimod may be associated with lower anti-spike protein-based immunoglobulin-G response following COVID-19 vaccination. We evaluated if COVID-19 occurred despite vaccination among patients with multiple sclerosis (MS) and neuromyelitis optica (NMO), using the COVISEP registry. Case series: We report 18 cases of COVID-19 after two doses of BNT162b2-vaccination, 13 of which treated with anti-CD20 and four with fingolimod. COVID-19 severity was mild. Discussion: These results reinforce the recommendation for a third COVID-19 vaccine dose among anti-CD20 treated patients and stress the need for a prospective clinical and biological study on COVID-19 vaccine efficacy among MS and NMO patients.
Published: 2021

119. Expertise en vue de la fixation de valeurs limites d’exposition à des agents chimiques en milieu professionnel. Évaluation des indicateurs biologiques d’exposition en vue de la recommandation de valeurs biologiques de référence pour le 2-méthoxy-1-propanol (n° CAS 1589-47-5) et l’acétate de 2-méthoxypropyle (n° CAS 70657-70-4)

Author: Viau, Claude, Marie-Desvergne, Caroline, Hopf, Nancy, Lelièvre, Bénédicte, Noisel, Nolwenn, Payan, Jean-Paul, Persoons, Renaud, Robert, Alain, Sari-Minodier, Irène, Antignac, Jean-Philippe, Delepee, Raphael, Garnier, Romain, Haddad, Sami, Mengelers, Marcel, Zeman, Florence, Lamkarkach, Farida, Brunet, Dominique, Rousselle, Christophe, Sissoko, Fatoumata, Université de Montréal (UdeM), CEA Cadarache, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre universitaire de médecine générale et santé publique (Unisanté), Université de Lausanne = University of Lausanne (UNIL), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], Institut national de recherche et de sécurité (Paris) (INRS (Paris)), CHU Grenoble, CHU Marseille, Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Caen Normandie (UNICAEN), Normandie Université (NU), Centre antipoison et de toxicovigilance (Paris) (CAPTV Paris), Université Paris Diderot - Paris 7 (UPD7)-Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Institut National de l'Environnement Industriel et des Risques (INERIS), Direction de l'Evaluation des Risques (DER), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), and Anses
Subjects: Exposure levels, [SDV]Life Sciences [q-bio], Chemical agents, Niveaux d’exposition, Occupational, PGME, Indicateurs biologiques d’exposition, Biomarkers of exposure, Propylene glycol methyl ether, Valeurs limites biologiques, Milieu professionnel, 2-methoxy-1- propanol, Agents chimiques, Biological limit values, Biological indicators of exposure, [SDV.TOX]Life Sciences [q-bio]/Toxicology, 1PG2ME, Propylène glycol méthyl éther, Limit values, Valeurs limites, 2-méthoxy-1-propanol
Abstract: Citation suggérée : Anses. (2022). Expertise en vue de la fixation de valeurs limites d’exposition à des agents chimiques en milieu professionnel. Évaluation des indicateurs biologiques d’exposition en vue de la recommandation de valeurs biologiques de référence pour le 2-méthoxy-1-propanol (n° CAS 1589-47-5) et l’acétate de 2-méthoxypropyle (n° CAS 70657-70-4). (saisine 2012-SA-0073). Maisons-Alfort : Anses, 56 p.; On 3 February 2012, Anses received a formal request from the French Directorate General for Labour (DGT) to conduct the expert appraisal work required for recommending biological monitoring in the workplace for 2-methoxy-1-propanol and its acetate, 2-methoxypropyl acetate. There are two isomers of propylene glycol monomethyl ether (PGME): 1-methoxy-2-propanol (2PG1ME or PGMEα, CAS No. 107-98-2) and 2-methoxy-1-propanol (1PG2ME or PGMEβ, CAS No. 1589-47-5); the respective acetates are 1-methoxy-2-propanol acetate (2PG1MEA or PGMAα, CAS No. 108-65-6) and 2-methoxypropyl acetate (1PG2MEA or PGMAβ, CAS No. 70657-70-4). In this report, 1-methoxy-2-propanol and its acetate will be referred to respectively as PGMEα and PGMAα while 2-methoxy-1-propanol and its acetate will be referred to as PGMEβ and PGMAβ.Since PGMEβ and its acetate are classified as reprotoxic (Category 1B) under the CLP Regulation, a concentration of at least 0.3% PGMEβ and/or PGMAβ in the commercial form of PGME results in a 1B reprotoxic classification. France does not currently have any occupational exposure limits for PGMEβ and its acetate. However, since 2007, PGMEα, as well as its acetate, have binding limit values, i.e. an 8h-OEL of 50 ppm and a 15min-STEL of 100 ppm.In an opinion published in 2008 (AFSSET 2008), AFSSET recommended, to “limit the risk of occupational exposure, strengthening biological surveillance in the workplace by developing markers for 2-methoxypropionic acid (2-MPA), the main metabolite of 1PG2ME and its acetate, and by systematically measuring urinary levels, instead of atmospheric levels, to be able to assess the overall exposure of workers”. The DGT thus asked ANSES to assess the relevance of recommending monitoring one or more biomarkers and the elaboration of biological limit values for the selected biomarker(s).; L’Anses a été saisie le 3 février 2012 par la direction générale du travail (DGT) afin de mener les travaux d’expertise nécessaires à la fixation de valeurs limites d’exposition professionnelle (VLEP) pour une dizaine de substances dont le 2-méthoxy-1-propanol et son acétate, l’acétate de 2-méthoxypropyle. Il existe deux isomères du propylène glycol monométhyléther (PGME) : le 1-méthoxy-2-propanol (2PG1ME ou PGMEα, CAS no 107-98-2) et le 2-méthoxy-1-propanol (1PG2ME ou PGMEβ, CAS no 1589-47-5), les acétates respectifs étant l’acétate de 1-méthoxy-2-propanol (2PG1MEA ou PGMAα, CAS no 108-65-6) et l’acétate de 2-méthoxypropyle (1PG2MEA ou PGMAβ, CAS no 70657-70-4). Le 1-méthoxy-2-propanol et son acétate seront désignés respectivement par les abréviations PGMEα et PGMAα, tandis que le 2-méthoxy-1-propanol et son acétate seront désignés respectivement par les abréviations PGMEβ et PGMAβ.Le PGMEβ et son acétate étant classés reprotoxiques (catégorie 1B) par le règlement CLP, la présence de PGMEβ et/ou PGMAβ dans la forme commerciale du PGME entraîne une classification reprotoxique 1B lorsque sa concentration est au moins égale 0,3 %. La France ne dispose à ce jour d’aucune valeur limite d’exposition professionnelle pour le PGMEβ et son acétate. Cependant, le PGMEα et son acétate disposent depuis 2007 de valeurs limites contraignantes, à savoir une VLEP-8h de 50 ppm et une VLCT-15 min de 100 ppm. Dans un avis publié en 2008 (AFSSET 20084 ), l’AFSSET a recommandé, pour « limiter le risque d’exposition en milieu professionnel, de renforcer la surveillance professionnelle biologique par le développement d’indicateurs pour l’acide 2-méthoxypropionique (2-MPA), métabolite principal du 1PG2ME et de son acétate, et par sa mesure urinaire systématique, à la place de la mesure atmosphérique, pour pouvoir évaluer les expositions globales des travailleurs ». Aussi la DGT a demandé à l’Anses d’évaluer le 2-méthoxy-1-propanol et son acétate afin d’établir la pertinence de recommander le suivi d’un ou plusieurs indicateurs biologiques et l’établissement de valeurs limites biologiques pour l’(les) indicateur(s) retenu(s).
Published: 2021

120. POCT-management during the first wave of Covid-19 in France. Results of a national survey leaded by the SFBC-POCT Working Group

Author: Glady, Ludovic, Moal, Valérie, Benz-de Bretagne, Isabelle, Bouvier, Damien, Di Giovanni, Flore, Chenevier-Gobeaux, Camille, Jeannesson, Elise, Jolly, Emilie, Kadi, Habiba, Oueidat, Nathalie, Pernet, Pascal, Pieroni, Laurence, Poupon, Carole, Toussaint-Hacquard, Marie, Dubos, Mickaël, Martinel, Isabelle, Chauzit, Emmanuelle, Beauvieux, Marie-Christine, Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand, CHU Marseille, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biochimie – Biologie moléculaire et Nutrition [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Hôpital Foch [Suresnes], Centre Hospitalier de Gonesse, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], CHU Tenon [AP-HP], Service d'Hématologie [CHRU Nancy], CHU Bordeaux [Bordeaux], Centre de résonance magnétique des systèmes biologiques (CRMSB), and Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience
Published: 2021

121. VITADIAL 'Does correction of 25 OH-VITAmin D with cholecalciferol supplementation increase muscle strength in hemoDIALysis patients?': study protocol for a randomized controlled trial

Author: Philippe Chauveau, Guillaume Seret, Marianne Serveaux, Frederic Lavainne, Laurence Vrigneaud, Mickaël Bobot, Thomas Robert, Guillaume Jean, Mathilde Prezelin-Reydit, Nathalie Pedinielli, Stanislas Bataille, Stéphanie Gentile, Elisabeth Jouve, Elisa Carreno, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Marseille, Institut phoceen de néphrologie, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), AURAD Aquitaine, Clinique Charcot, Institut Polytechnique de Paris (IP Paris), Association ECHO [Expansion des Centres d’Hémodialyse de l’Ouest], Hôpital Nord [CHU - APHM], Polyclinique de l’Atlantique, Partenaires INRAE, Phocean Nephrology Institute, Ramsay Générale de Santé - Hôpital Privé La Louvière, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), and Lucas, Nelly
Subjects: medicine.medical_specialty, Medicine (General), Randomization, medicine.medical_treatment, Population, 030232 urology & nephrology, Medicine (miscellaneous), law.invention, Study Protocol, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, R5-920, Meta-Analysis as Topic, Randomized controlled trial, Renal Dialysis, law, Internal medicine, medicine, Vitamin D and neurology, Humans, Multicenter Studies as Topic, Pharmacology (medical), Muscle Strength, Prospective Studies, 030212 general & internal medicine, Vitamin D, education, Aged, Cholecalciferol, Randomized Controlled Trials as Topic, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Hand Strength, business.industry, Vitamin D Deficiency, medicine.disease, 3. Good health, chemistry, Dietary Supplements, Cohort, Quality of Life, Hemodialysis, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Kidney disease
Abstract: Background Muscle strength decreases as kidney failure progresses. Low muscle strength affects more than 50% of hemodialysis patients and leads to daily life activities impairment. In the general population, numerous studies have linked low 25OH-vitamin D (25OHD) concentrations to the loss of the muscle strength and low physical performances. Data on native vitamin D and muscle function are scarce in the chronic kidney disease (CKD) population, but low 25OHD levels have been associated with poor muscle strength. We present in this article the protocol of an ongoing study named VITADIAL testing if cholecalciferol supplementation in hemodialysis patients with low 25OHD improves their muscle strength. Methods/design VITADIAL is a prospective open randomized French multicenter study. All patients will have 25OHD levels ≤50nmol/L at randomization. One group will receive 100,000 UI cholecalciferol once a month during 6 months; the other group will receive no treatment during 6 months. In order to randomize patients with 25OHD ≤50nmol/L, supplemented patients will undergo a 3 months wash-out period renewable 3 times (maximum of 12 months wash-out) until 25OHD reaches a level ≤50nmol/L. The main objective of this study is to analyze if a 6-month period of oral cholecalciferol (i.e., native vitamin D) supplementation improves muscle strength of hemodialysis patients with low 25OHD vitamin D levels. Muscle strength will be assessed at 0, 3, and 6 months, by handgrip strength measured with a quantitative dynamometer. Secondary objectives are (1) to analyze 25OHD plasma levels after vitamin D wash-out and/or supplementation, as well as factors associated with 25OHD lowering speed during wash-out, and (2) to analyze if this supplementation improves patient’s autonomy, reduces frailty risk, and improves quality of life. Fifty-four patients are needed in each group to meet our main objective. Discussion In the general population, around 30 randomized studies analyzed the effects of vitamin D supplementation on muscle strength. These studies had very different designs, sizes, and studied population. Globally, these studies and the meta-analysis of studies favor a beneficial effect of vitamin D supplementation on muscle strength, but this effect is mainly found in the subgroup of aged patients and those with the lowest 25OHD concentrations at inclusion. We reported a positive independent association between 25OHD and handgrip strength in a population of 130 hemodialysis patients in a dose-dependent manner. In our cohort, a plateau effect was observed above 75 nmol/L. Only two randomized studies analyzed the effect of native vitamin D supplementation on muscle strength in hemodialysis patients, but unfortunately, these two studies were underpowered. VITADIAL is a trial specifically designed to assess whether cholecalciferol might benefit to hemodialysis patient’s muscle strength. Trial registration ClinicalTrials.govNCT04262934. Registered on 10 February 2020 - Retrospectively registered.
Published: 2021

122. Subthalamic stimulation breaks the balance between distal and axial signs in Parkinson’s disease

Author: Serge Pinto, Christelle Baunez, Cyril Atkinson-Clement, Thierry Legou, Tatiana Witjas, Jean-Philippe Azulay, Alexandre Zénon, Frédérique Fluchère, Émilie Cavazzini, Alexandre Eusebio, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Parole et Langage (LPL), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Neurosciences de la Timone (INT), CHU Marseille, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_specialty, Parkinson's disease, Deep brain stimulation, Deep Brain Stimulation, Science, medicine.medical_treatment, behavioral disciplines and activities, Article, Antiparkinson Agents, Levodopa, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Reward, Quality of life, Vowel, Humans, Medicine, Phonation, Aged, 030304 developmental biology, Balance (ability), Motivation, 0303 health sciences, Multidisciplinary, business.industry, Parkinson Disease, Middle Aged, medicine.disease, nervous system diseases, Treatment Outcome, surgical procedures, operative, nervous system, Subthalamus, Subthalamic stimulation, Basal ganglia, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, therapeutics, 030217 neurology & neurosurgery
Abstract: In Parkinson’s disease (PD), the effects of both Ldopa and subthalamic deep brain stimulation (STN-DBS) are known to change cost-valuation. However, this was mostly studied through reward-effort task involving distal movements, while axial effort, less responsive to treatments, have been barely studied. Thus, our objective was to compare the influence of both Ldopa and STN-DBS on cost-valuation between two efforts modalities: vowel production (as an example of axial movement) and hand squeezing (as an example of distal movement). Twelve PD patients were recruited to participate in this study. The task consisted in deciding whether to accept or reject trials based on a reward-effort trade-off. Participants performed two blocks with hand squeezing, and two with vowel production, in the four treatment conditions (LdopaOn/Off; STN-DBS On/Off). We found that STN-DBS changed the ratio difference between hand and phonation efforts. Vowel production effort was estimated easier to perform with STN-DBS alone, and harder when associated with Ldopa. The difference between hand and phonation efforts was correlated with quality of life in Off/Off and On Ldopa alone conditions, and with impulsive assessment On STN-DBS alone. We highlighted that STN-DBS could introduce an imbalance between the actual motor impairments and their subjective costs. With this finding, we also suggest paying particular attention to the different treatment effects that should be expected for axial and distal movement dysfunctions.
Published: 2021

123. Comparative Risk of Incident Cancer in Patients with Inflammatory Bowel Disease with Prior Non-digestive Malignancy According to Immunomodulator: a Multicentre Cohort Study

Author: F Poullenot, A Amiot, M Nachury, S Viennot, R Altwegg, Y Bouhnik, V Abitbol, S Nancey, L Vuitton, L Peyrin-Biroulet, A Biron, M Fumery, L Picon, M Vidon, C Reenaers, M Serrero, G Savoye, L Beaugerie, P Rivière, D Laharie, CHU Bordeaux [Bordeaux], CHU Henri Mondor [Créteil], Hôpital Claude Huriez [Lille], CHU Lille, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Clichy, Service de Gastro-entérologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, Centre Hospitalier Universitaire de Liège (CHU-Liège), CHU Marseille, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'hépato-gastroentérologie, CHU Strasbourg-Hopital Civil, Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, incident cancer, Adolescent, IBD, Gastroenterology, General Medicine, Inflammatory Bowel Diseases, incident-cancer free survival, Cohort Studies, Gastrointestinal Agents, Inflammatory Bowel Diseases/drug therapy, Neoplasms, Neoplasms/chemically induced, Gastrointestinal Agents/therapeutic use, cancer, Immunosuppressive Agents/therapeutic use, Humans, Female, Tumor Necrosis Factor Inhibitors, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Immunosuppressive Agents, Retrospective Studies
Abstract: Introduction Knowledge about the cancer risk when initiating a biologic in inflammatory bowel disease [IBD] patients with prior malignancy remains scarce, especially for vedolizumab. Our aim was to evaluate the rate of incident cancer in a cohort of IBD patients with prior non-digestive malignancy, according to the subsequent treatment given. Methods A multicentre retrospective study included consecutive IBD patients with prior non-digestive malignancy. Inclusion date corresponded to the diagnosis of index malignancy. Patients were categorized into different cohorts according to the first treatment [none, conventional immunosuppressant, anti-TNF, or vedolizumab] to which they were exposed after inclusion and before incident cancer [recurrent or new cancer]. Results Among the 538 patients {58% female; mean (standard deviation [SD]) age inclusion: 52 [15] years} analyzed, the most frequent malignancy was breast cancer [25%]. The first immunomodulator given after inclusion was a conventional immunosuppressant in 27% of patients, anti-TNF in 21%, or vedolizumab in 9%. With a median (interquartile range [IQR]) follow-up duration of 55 [23-100] months, 100 incident cancers were observed. Crude cancer incidence rates per 1000 person-years were 47.0 for patients receiving no immunomodulator, 36.6 in the anti-TNF cohort, and 33.6 in the vedolizumab cohort [p = 0.23]. Incident-cancer free survival rates were not different between patients receiving anti-TNF and those receiving vedolizumab [p = 0.56]. After adjustment, incidence rates were not different between patients receiving no immunomodulator, anti-TNF, or vedolizumab. Conclusions In this large multicentre cohort study, there was no difference of cancer incidence in those IBD patients with prior non-digestive malignancy, treated with vedolizumab or anti-TNF.
Published: 2021

124. Association Between Early Amino Acid Intake and Full-Scale IQ at Age 5 Years Among Infants Born at Less Than 30 Weeks’ Gestation

Author: Jean-Christophe, Rozé, Baptiste, Morel, Alexandre, Lapillonne, Stéphane, Marret, Isabelle, Guellec, Dominique, Darmaun, Nathalie, Bednarek, Thomas, Moyon, Laetitia, Marchand-Martin, Valérie, Benhammou, Véronique, Pierrat, Cyril, Flamant, Géraldine, Gascoin, Delphine, Mitanchez, Gilles, Cambonie, Laurent, Storme, Bathélémie, Tosello, Valérie, Biran, Olivier, Claris, Jean-Charles, Picaud, Géraldine, Favrais, Alain, Beuchée, Gauthier, Loron, Catherine, Gire, Xavier, Durrmeyer, Pierre, Gressens, Elie, Saliba, Pierre-Yves, Ancel, Catherine, Adamsbaum, Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'épidémiologie Clinique [Hôtel-Dieu], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Hôtel Dieu, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Rouen, Normandie Université (NU), Service de néonatologie [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche en Sciences et Technologies de l'Information et de la Communication - EA 3804 (CRESTIC), Université de Reims Champagne-Ardenne (URCA), Centre Hospitalier Universitaire de Reims (CHU Reims), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Lille, CHU Trousseau [Tours], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), CHU Marseille, AP-HP Hôpital universitaire Robert-Debré [Paris], Hospices Civils de Lyon (HCL), CHU Pontchaillou [Rennes], Centre Hospitalier Intercommunal de Créteil (CHIC), CIC - Mère Enfant Necker Cochin Paris Centre (CIC 1419), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Nutrition EPIPAGE-2 Study Group and the EPIRMEX Study Group: Farid Bourdred, Odile Dicky, Jean-Michel Hascoet, Gerard Thiriez, Luc Desfrere, Clement Chollat, Isabelle Filipiak, Dominique Sirinelli, Alexandre Chadi, Catherine Adamsbaum, HAL-SU, Gestionnaire, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: Male, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Research, Intelligence, Infant, Newborn, Infant, Gestational Age, Infant, Premature, Diseases, Pediatrics, Cohort Studies, Online Only, Child Development, Treatment Outcome, Child, Preschool, Practice Guidelines as Topic, Humans, Female, France, Prospective Studies, Amino Acids, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Original Investigation
Abstract: Key Points Question Is early amino acid intake among very preterm infants associated with cognitive performance at age 5 years? Findings In this cohort study of 1789 infants born at less than 30 weeks’ gestation, exposure vs nonexposure to amino acid intake between 3.51 and 4.50 g/kg/d at 7 days after birth was significantly and independently associated with a higher likelihood (61% vs 54%, respectively) of surviving with a full-scale IQ score greater than −1 SD at age 5 years. Meaning The results of this study suggest that high early amino acid intake among very preterm infants is safe and significantly associated with improved cognitive outcomes at age 5 years., Importance An international expert committee recently revised its recommendations on amino acid intake for very preterm infants, suggesting that more than 3.50 g/kg/d should be administered only to preterm infants in clinical trials. However, the optimal amino acid intake during the first week after birth in these infants is unknown. Objective To evaluate the association between early amino acid intake and cognitive outcomes at age 5 years. Design, Setting, and Participants Using the EPIPAGE-2 (Epidemiologic Study on Small-for-Gestational-Age Children—Follow-up at Five and a Half Years) cohort, a nationwide prospective population-based cohort study conducted at 63 neonatal intensive care units in France, a propensity score–matched analysis was performed comparing infants born at less than 30 weeks’ gestation who had high amino acid intake (3.51-4.50 g/kg/d) at 7 days after birth with infants who did not. Participants were recruited between April 1 and December 31, 2011, and followed up from September 1, 2016, to December 31, 2017. Full-scale IQ (FSIQ) was assessed at age 5 years. A confirmatory analysis used neonatal intensive care unit preference for high early amino acid intake as an instrumental variable to account for unmeasured confounding. Statistical analysis was performed from January 15 to May 15, 2021. Exposures Amino acid intake at 7 days after birth. Main Outcomes and Measures The primary outcome was an FSIQ score greater than −1 SD (ie, ≥93 points) at age 5 years. A complementary analysis was performed to explore the association between amino acid intake at day 7 as a continuous variable and FSIQ score at age 5 years. Data from cerebral magnetic resonance imaging at term were available for a subgroup of preterm infants who participated in the EPIRMEX (Cerebral Abnormalities Detected by MRI, Realized at the Age of Term and the Emergence of Executive Functions) ancillary study. Results Among 1789 preterm infants (929 boys [51.9%]; mean [SD] gestational age, 27.17 [1.50] weeks) with data available to determine exposure to amino acid intake of 3.51 to 4.50 g/kg/d at 7 days after birth, 938 infants were exposed, and 851 infants were not; 717 infants from each group could be paired. The primary outcome was known in 396 of 646 exposed infants and 379 of 644 nonexposed infants who were alive at age 5 years and was observed more frequently among exposed vs nonexposed infants (243 infants [61.4%] vs 206 infants [54.4%], respectively; odds ratio [OR], 1.33 [95% CI, 1.00-1.71]; absolute risk increase in events [ie, the likelihood of having an FSIQ score >−1 SD at age 5 years] per 100 infants, 7.01 [95% CI, 0.06-13.87]; P = .048). In the matched cohort, correlation was found between amino acid intake per 1.00 g/kg/d at day 7 and FSIQ score at age 5 years (n = 775; β = 2.43 per 1-point increase in FSIQ; 95% CI, 0.27-4.59; P = .03), white matter area (n = 134; β = 144 per mm2; 95% CI, 3-285 per mm2; P = .045), anisotropy of the corpus callosum (n = 50; β = 0.018; 95% CI, 0.016-0.021; P, This cohort study assesses the association between high amino acid intake among very preterm infants at 7 days after birth and cognitive performance at age 5 years.
Published: 2021

125. 10 years of CEMARA database in the AnDDI-Rares network: a unique resource facilitating research and epidemiology in developmental disorders in France

Author: MESSIAEN, Claude, RACINE, Caroline, KHATIM, Ahlem, SOUSSAND, Louis, ODENT, Sylvie, LACOMBE, Didier, MANOUVRIER, Sylvie, EDERY, Patrick, SIGAUDY, Sabine, GENEVIEVE, David, THAUVIN-ROBINET, Christel, PASQUIER, Laurent, PETIT, Florence, ROSSI, Massimiliano, WILLEMS, Marjolaine, ATTIE-BITACH, Tania, ROUX-LEVY, Pierre-Henry, DEMOUGEOT, Laurent, BEN SLAMA, Lilia, LANDAIS, Paul, THE ANDDI-RARES, Network, JANNOT, Anne-Sophie, BINQUET, Christine, SANDRIN, Arnaud, VERLOES, Alain, FAIVRE, Laurence, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Pontchaillou [Rennes], Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], CHU Lille, Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 (RADEME), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), CHU Marseille, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, FHU TRANSLAD (CHU de Dijon), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université de Montpellier (UM), GHU AP-HP Centre Université de Paris, Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Robert Debré, Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Montpellier, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)
Subjects: Adult, 0301 basic medicine, medicine.medical_specialty, Resource (biology), Databases, Factual, Epidemiology, Developmental Disabilities, Population, 030105 genetics & heredity, computer.software_genre, 03 medical and health sciences, Rare Diseases, 0302 clinical medicine, Data warehouse, Care organization, Humans, Medicine, Pharmacology (medical), 030212 general & internal medicine, Medical diagnosis, Child, education, Genetics (clinical), Retrospective Studies, education.field_of_study, Database, business.industry, Research, Developmental disorders, General Medicine, 3. Good health, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Uncertain diagnosis, Christian ministry, France, business, computer, Rare disease, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background In France, the Ministry of Health has implemented a comprehensive program for rare diseases (RD) that includes an epidemiological program as well as the establishment of expert centers for the clinical care of patients with RD. Since 2007, most of these centers have entered the data for patients with developmental disorders into the CEMARA population-based registry, a national online data repository for all rare diseases. Through the CEMARA web portal, descriptive demographic data, clinical data, and the chronology of medical follow-up can be obtained for each center. We address the interest and ongoing challenges of this national data collection system 10 years after its implementation. Methods Since 2007, clinicians and researchers have reported the “minimum dataset (MDS)” for each patient presenting to their expert center. We retrospectively analyzed administrative data, demographic data, care organization and diagnoses. Results Over 10 years, 228,243 RD patients (including healthy carriers and family members for whom experts denied any suspicion of RD) have visited an expert center. Among them, 167,361 were patients affected by a RD (median age 11 years, 54% children, 46% adults, with a balanced sex ratio), and 60,882 were unaffected relatives (median age 37 years). The majority of patients (87%) were seen no more than once a year, and 52% of visits were for a diagnostic procedure. Among the 2,869 recorded rare disorders, 1,907 (66.5%) were recorded in less than 10 patients, 802 (28%) in 10 to 100 patients, 149 (5.2%) in 100 to 1,000 patients, and 11 (0.4%) in > 1,000 patients. Overall, 45.6% of individuals had no diagnosis and 6.7% had an uncertain diagnosis. Children were mainly referred by their pediatrician (46%; n = 55,755 among the 121,136 total children referrals) and adults by a medical specialist (34%; n = 14,053 among the 41,564 total adult referrals). Given the geographical coverage of the centers, the median distance from the patient’s home was 25.1 km (IQR = 6.3 km-64.2 km). Conclusions CEMARA provides unprecedented support for epidemiological, clinical and therapeutic studies in the field of RD. Researchers can benefit from the national scope of CEMARA data, but also focus on specific diseases or patient subgroups. While this endeavor has been a major collective effort among French RD experts to gather large-scale data into a single database, it provides tremendous potential to improve patient care.
Published: 2021

126. Successful treatment with adapted high dose methotrexate in a hemodialysis patient with primary central nervous system lymphoma: 100 mg/m2 seems sufficient

Author: Solignac, Justine, Farnault, Laure, Robert, Thomas, Fanciullino, Raphaelle, Choquet, Sylvain, Brunet, Philippe, Venton, Geoffroy, Bobot, Mickaël, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Timone [CHU - APHM] (TIMONE), Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Simulation and Modeling of Adaptive Response for Therapeutics in Cancer (SMARTc), Centre de Recherche en Cancérologie de Marseille (CRCM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), CHU Marseille, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Assistance Publique - Hôpitaux de Marseille (APHM), Aix Marseille Université (AMU), and Lucas, Nelly
Subjects: musculoskeletal diseases, Pediatrics, medicine.medical_specialty, Lymphoma, medicine.medical_treatment, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Hemodialysis status, 030204 cardiovascular system & hematology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Metotrexato, 03 medical and health sciences, Drug toxicity, 0302 clinical medicine, Chemoimmunotherapy, medicine, Hemodiálisis, business.industry, Primary central nervous system lymphoma, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, High dose methotrexate, 3. Good health, Methotrexate, Linfoma, Sistema nervioso central, Nephrology, Central nervous system, 030220 oncology & carcinogenesis, Hemodialysis, Toxicity, business, Toxicidad farmacológica, medicine.drug
Abstract: International audience; High dose methotrexate (HD-MTX) based chemoimmunotherapy is a central part of the standard approach to treatment of primary central nervous system lymphoma (PCNSL). Renal dysfunction leads to delayed MTX complete elimination and critical MTX concentration. Despite the recommendations, hemodialysis status should not exclude HD-MTX. We report the case of a 64 years old woman on chronic hemodialysis with PCNSL successfully treated with HD-MTX-based chemoimmunotherapy with an adjusted dose of 100 mg/m(2), instead of the usual dose of 3500 mg/m(2), and daily hemodialysis started 24 h later. The patient had no significant toxicity and was in complete remission at 1 year after the end of the treatment. We argue that ESRD is not an absolute pitfall to the use of HD-MTX for hematological malignancies. Experts should consider the use of adjusted dose at 100 mg/m(2) as a viable therapeutic modality in ESRD patients. (C) 2021 Sociedad Espanola de Nefrologia. Published by Elsevier Espana, S.L.U.
Published: 2021

127. Association between Leflunomide and Pulmonary Hypertension

Author: Thomas Lacoste Palasset, Sophie Bulifon, Xavier Jaïs, Laurent Savale, Laurent Bertoletti, Gérald Simonneau, Marie-Camille Chaumais, Martine Reynaud-Gaubert, Céline Chabanne, Mathilde Volpato, Frédéric Perros, Grégoire Manaud, Laura C. Price, Kais Ahmad, Nicolas Favrolt, O. Sitbon, Anne Guillaumot, Athénaïs Boucly, Jason Weatherald, Nicolas Lamblin, Grégoire Prévot, Pierre Fesler, Charles Khouri, David Montani, Andrei Seferian, Delphine Horeau-Langlard, Stefana Pancic, Mitja Jevnikar, David Launay, Marc Humbert, Pôle des Cardiopathies Congénitales du Nouveau-Né à L'adulte - Centre Constitutif Cardiopathies Congénitales Complexes M3C, Groupe Hospitalier Paris Saint-Joseph, Hôpital Marie-Lannelongue, Inserm U999, Université Paris-Saclay, Imperial College London, Centre Hospitalier Universitaire [Grenoble] (CHU), University of Calgary, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Biologie intégrative du tissu osseux, Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Saint Etienne, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Nord (Saint Etienne), CHU Marseille, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), MORNET, Dominique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Toulouse [Toulouse], Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Nord (Saint Etienne), Biologie Intégrative du Tissu Osseux (LBTO), Centre d'Investigation Clinique - Epidémiologie Clinique Saint-Etienne (CIC-EC), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Pulmonary and Respiratory Medicine, Cardiac Catheterization, medicine.medical_specialty, antirheumatic agents, Hypertension, Pulmonary, [SDV]Life Sciences [q-bio], Cardiac index, Hemodynamics, 030204 cardiovascular system & hematology, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Pharmacovigilance, pulmonary hypertension, medicine, Humans, Risk factor, Lung, Leflunomide, business.industry, Endothelial Cells, medicine.disease, Pulmonary hypertension, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, 030228 respiratory system, pharmacovigilance, Toxicity, translational medical research, Vascular resistance, business, medicine.drug
Abstract: International audience; Rationale: Pulmonary hypertension (PH) has been described in patients treated with leflunomide. Objectives: To assess the association between leflunomide and PH. Methods: We identified incident cases of PH in patients treated with leflunomide from the French PH Registry and through the pharmacoVIGIlAnce in Pulmonary ArTerial Hypertension (VIGIAPATH) program between September 1999 to December 2019. PH etiology, clinical, functional, radiologic, and hemodynamic characteristics were reviewed at baseline and follow-up. A pharmacovigilance disproportionality analysis using the World Health Organization's global database was conducted. We then investigated the effect of leflunomide on human pulmonary endothelial cells. Data are expressed as median (min-max). Results: Twenty-eight patients treated with leflunomide before PH diagnosis was identified. A total of 21 (75%) had another risk factor for PH and 2 had two risk factors. The median time between leflunomide initiation and PH diagnosis was 32 months (1-120). Right heart catheterization confirmed precapillary PH with a cardiac index of 2.37 L⋅min-1 ⋅m-2 (1.19-3.1) and elevated pulmonary vascular resistance at 9.63 Wood Units (3.6-22.1) without nitric oxide reversibility. Five patients (17.9%) had no other risk factor for PH besides exposure to leflunomide. No significant hemodynamic improvement was observed after leflunomide withdrawal. The pharmacovigilance disproportionality analysis using the World Health Organization's database revealed a significant overrepresentation of leflunomide among reported pulmonary arterial hypertension-adverse drug reactions. In vitro studies showed the dose-dependent toxicity of leflunomide on human pulmonary endothelial cells. Conclusions: PH associated with leflunomide is rare and usually associated with other risk factors. The pharmacovigilance analysis suggests an association reinforced by experimental data.
Published: 2021

128. Comparison between Immunocytochemistry, FISH and NGS for ALK and ROS1 Rearrangement Detection in Cytological Samples

Author: Diane Frankel, Isabelle Nanni, L’Houcine Ouafik, Clara Camilla, Eric Pellegrino, Nathalie Beaufils, Laurent Greillier, Hervé Dutau, Philippe Astoul, Elise Kaspi, Patrice Roll, Ouafik, L'Houcine, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Nord [CHU - APHM], Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), CHU Marseille, and Aix Marseille Université (AMU)
Subjects: MESH: Gene Rearrangement, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Protein-Tyrosine Kinases, Catalysis, Inorganic Chemistry, immunocytochemistry, FISH, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH: In Situ Hybridization, Fluorescence, Physical and Theoretical Chemistry, MESH: High-Throughput Nucleotide Sequencing, Molecular Biology, Spectroscopy, MESH: Anaplastic Lymphoma Kinase, adenocarcinoma, MESH: Humans, NGS, ALK, ROS1, lung cancer, cytology, Organic Chemistry, MESH: Retrospective Studies, MESH: Immunohistochemistry, General Medicine, MESH: Lung Neoplasms, Computer Science Applications, MESH: Proto-Oncogene Proteins, MESH: Carcinoma, Non-Small-Cell Lung
Abstract: International audience; The detection of ROS1 and ALK rearrangements is performed for advanced-stage non-small cell lung cancer. Several techniques can be used on cytological samples, such as immunocytochemistry (ICC), fluorescence in situ hybridization (FISH) and, more recently, next-generation sequencing (NGS), which is gradually becoming the gold standard. We performed a retrospective study to compare ALK and ROS1 rearrangement results from immunocytochemistry, FISH and NGS methods from 131 cytological samples. Compared to NGS, the sensitivity and specificity of ICC were 0.79 and 0.91, respectively, for ALK, and 1 and 0.87 for ROS1. Regarding FISH, the sensitivity and specificity were both at 1 for ALK and ROS1 probes. False-positive cases obtained by ICC were systematically corrected by FISH. When using ICC and FISH techniques, results are very close to NGS. The false-positive cases obtained by ICC are corrected by FISH, and the true-positive cases are confirmed. NGS has the potential to improve the detection of ALK and ROS1 rearrangements in cytological samples; however, the cost of this technique is still much higher than the sequential use of ICC and FISH.
Published: 2022

129. Acute acral eruptions in children during the COVID-19 pandemic: Characteristics of 103 children and their family clusters

Author: Catherine McCuaig, A. Phan, A. Labarelle, M. Bissuel, Annabel Maruani, Sébastien Barbarot, A. Bellissen, Maryam Piram, Stéphanie Mallet, Bruno Giraudeau, Denis Jullien, L. Monitor, J. Rapp, S. Leducq, Ludovic Martin, Pierre Vabres, Christine Chiaverini, C Lesort, Audrey Lasek, Thomas Hubiche, Hélène Aubert, I. Nicol, L. Fertitta, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), CHU Marseille, CHU Sainte Justine [Montréal], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Edouard Herriot [CHU - HCL], CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), and Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques
Subjects: Male, Vasculitis, Acral erythema, Coronavirus disease 2019 (COVID-19), Adolescent, Hidradenitis, Mucinoses, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], Dermatology, Serology, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Pandemic, medicine, Humans, Family, Lymphocytes, Chilblains, Child, Children, Pandemics, Retrospective Studies, Skin, business.industry, COVID-19, medicine.disease, 3. Good health, Multicenter study, Erythema, Antibodies, Antinuclear, Immunoglobulin G, Observational study, Original Article, Female, business, Demography, Familial transmission
Abstract: Background A marked increase in frequency of acute acral eruptions (AAE) was observed in children during the COVID-19 pandemic in the spring period. Objectives In this observational multicenter study, based on children with AAE, we aimed to assess the proportion of household members possibly infected by SARS-CoV-2. Methods We collected data from all children observed with AAE, prospectively from April 7, 2020 to June 22, 2020, and retrospectively since February 28, 2020. The primary outcome was the household infection rate, defined as the proportion of family clusters having at least one member with COVID-19 infection other than the child with AAE (“index child”). The definition of a case was based on characteristic clinical signs and a positive PCR or serology. Results The study included 103 children in 10 French departments and in Quebec. The median age was 13 years and the interquartile range [8–15], with a female-to-male ratio of 1/1.15. In children with AAE, all PCR tests were negative (n = 18), and serology was positive in 2/14 (14.3%) cases. We found no significant anomalies in the lab results. A total of 66 of the 103 families (64.1%) of included children had at least one other infected member apart from the index child. The total number of household members was 292, of whom 119 (40.8%) were considered possibly infected by SARS-CoV-2. No index children or households exhibited severe COVID-19. Discussion Among the 103 households included, 64.1% had at least one infected member. Neither children with AAE nor their households showed severe COVID-19.
Published: 2021

130. A Meta-Analysis of Semantic Memory in Mild Cognitive Impairment

Author: Ludovic Gardy, Emmanuel J. Barbeau, Mira Didic, Sven Joubert, Isabelle Rouleau, Centre de Recherche de l'Institut Universitaire de Gériatrie de Montréal (CRIUGM), Centre de recherche cerveau et cognition (CERCO UMR5549), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Service de neurochirurgie [CHU Marseille], Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université du Québec à Montréal = University of Québec in Montréal (UQAM), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Neurology, Cognitive Neuroscience, naming, [SHS.PSY]Humanities and Social Sciences/Psychology, Experimental and Cognitive Psychology, Audiology, behavioral disciplines and activities, 050105 experimental psychology, Mini Mental Status Examination, [SHS]Humanities and Social Sciences, 03 medical and health sciences, 0302 clinical medicine, Arts and Humanities (miscellaneous), mental disorders, medicine, Developmental and Educational Psychology, Semantic memory, 0501 psychology and cognitive sciences, 10. No inequality, Cognitive impairment, semantic memory, 05 social sciences, Neuropsychology, Alzheimer's disease, Random effects model, MCI, Feature (linguistics), meta-analysis, Neuropsychology and Physiological Psychology, Meta-analysis, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Psychology, 030217 neurology & neurosurgery, Cognitive psychology
Abstract: International audience; Introduction: Accumulating evidence over the past decade suggests that semantic deficits represent a consistent feature of Mild Cognitive Impairment (MCI). A meta-analysis was performed to examine if semantic deficits are consistently found in patients with MCI. Methods: Studies meeting all inclusion criteria were selected for the current meta-analysis. An effect size and a weight were calculated for each study. A random effect model was performed to assess the overall difference in semantic performances between MCI patients and healthy subjects. Results: 22 studies (476 healthy participants, 476 MCI patients, mean MMSE of the MCI patients: 27.05 ± 0.58) were included in the meta-analysis. Results indicate that MCI patients systematically performed significantly worse than healthy matched controls in terms of overall semantic performance (mean effect size of 1.02; 95% CI [0.80; 1.24]). Discussion: Semantic deficits are a key feature of MCI. Semantic tests should be incorporated in routine clinical assessments.
Published: 2021

131. Les femmes ménopausées : recommandations pour la pratique clinique du CNGOF et du GEMVi (Texte court)

Author: J.-M. Pouillès, Nathalie Chabbert-Buffet, G. Boutet, Carole Mathelin, E. Maris, Lorraine Maitrot-Mantelet, C. Hocke, Geneviève Plu-Bureau, G. André, Florence Trémollières, M. Duclos, G. Robin, A. Gosset, Olivier Graesslin, J.-M. Lecerf, P. Lopes, Justine Hugon-Rodin, Naima Hamdaoui, Christine Rousset-Jablonski, Xavier Fritel, CHU Toulouse [Toulouse], Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Unité de Gynécologie Médicale, AP-HP, Hôpital Port-Royal, Université de Paris, Sorbonne Paris Nord University, INSERM U1153, INRAE U1125, CNAM, Nutritional Epidemiology Research Team (EREN), Epidemiology and Statistics Research Center-University of Paris (CRESS), Ctr Leon Berard, Université de Lyon, Hospices Civils de Lyon (HCL), Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service Médecine du Sport et Explorations Fonctionnelles [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, CHU Bordeaux [Bordeaux], Université de Montpellier (UM), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Lille, CHU Marseille, Institut de Cancérologie de Strasbourg Europe (ICANS), Les Hôpitaux Universitaires de Strasbourg (HUS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), France Polyclin Atlantique St Herblain, Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Mère Enfant Alix de Champagne, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Centre Léon Bérard [Lyon]
Subjects: medicine.medical_specialty, 030219 obstetrics & reproductive medicine, Postmenopausal women, business.industry, Obstetrics and Gynecology, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 3. Good health, Clinical Practice, 03 medical and health sciences, 0302 clinical medicine, Reproductive Medicine, 030220 oncology & carcinogenesis, Family medicine, Medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2021

132. Determinants of IBD-related disability: a cross-sectional survey from the GETAID

Author: Tannoury, Jenny, Nachury, Maria, Martins, Carole, Serrero, Melanie, Filippi, Jerome, Roblin, Xavier, Bourrier, Anne, Bouguen, Guillaume, Franchimont, Denis, Savoye, Guillaume, Buisson, Anthony, Louis, Edouard, Nancey, Stephane, Abitbol, Vered, Reimund, Jean-Marie, DeWitt, Olivier, Vuitton, Lucine, Mathieu, Nicolas, Peyrin-Biroulet, Laurent, Gilletta, Cyrielle, Allez, Matthieu, Viennot, Stephanie, Trang-Poisson, Caroline, Laharie, David, Amiot, Aurelien, GETAID, Groupe d'Etude Thérapeutique des Affections, Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Clichy, CHU Marseille, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), CHU Clermont-Ferrand, Centre Hospitalier Universitaire de Liège (CHU-Liège), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Strasbourg, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Bordeaux [Bordeaux], AbbVie, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), CHU Toulouse [Toulouse], Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, digestive system diseases
Abstract: International audience; Background: The burden of inflammatory bowel disease (IBD) is rising worldwide. The goal of IBD treatment is to achieve clinical and endoscopic remission but also prevent disability.Aims: To identify the predictive factors of disability in a large population of patients with IBD.Patients and methods: We conducted a cross-sectional survey in 42 tertiary centres in France and Belgium. A self-administered questionnaire was designed to explore patients and their IBD characteristics. IBD-disk is a validated tool to measure disability in patients with IBD. The IBD-disk score was then calculated for each patient. Based on a previous study, an overall IBD-disk score ≥40 was associated with moderate-to-severe disability.Results: Among the 2011 patients, 1700 were analysed, including 746 (44%) in self-reported clinical remission and 752 (44.2%) declaring clinical activity. The patient global assessment of global remission was missing in 200 (11.8%) of 1700 patients. Moderate-to-severe disability was significantly increased in patients with BMI >25 kg/m2 (OR = 1.66; 95% CI [1.29-2.14]), in those having perception of need for a psychotherapist (OR = 2.24; 95% CI [1.79-3.05]) and social worker (OR = 1.54; 95% CI [1.08-2.21]). Conversely, male gender (OR = 0.83; 95% CI [0.69-0.99]), ulcerative colitis (OR = 0.69; 95% CI [0.53-0.92]), self-reported clinical remission (OR = 0.59; 95% CI [0.46-0.77]) and employed or student occupational status (OR = 0.69; 95% CI [0.52-0.92]) were inversely correlated with disability. Overall, 257 (34.5%) patients who declared being in clinical remission had disability.Conclusion: Determinants of IBD-related disability include IBD-related factors but also psychological and social factors. This highlights the importance of a multidisciplinary team in the management of patients with IBD.
Published: 2021

133. Rational and Design of the SIMULATOR Study: A Multicentre Randomized Study to Assess the Impact of SIMULation-bAsed Training on Transoesophageal echocardiOgraphy leaRning for Cardiology Residents

Author: Théo Pezel, Anne Bernard, Yoan Lavie Badie, Julien Dreyfus, Etienne Audureau, Yohann Bohbot, Damien Fard, Arnaud Hubert, Lee S. Nguyen, Cécile Monteil, Loïc Bière, Florent Le Ven, Marjorie Canu, Sophie Ribeyrolles, Baptiste Mion, Basile Mouhat, Baptiste Bazire, Charles Fauvel, Julien Ternacle, Jennifer Cautela, Théo Cambet, Thierry Le Tourneau, Erwan Donal, Stéphane Lafitte, Nicolas Mansencal, Augustin Coisne, Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Johns Hopkins University (JHU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours-Hôpital Bretonneau, Faculté de Médecine, Université de Tours, Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre cardiologique du Nord (CCN), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor, CHU Amiens-Picardie, Université de Picardie Jules Verne (UPJV), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Ambroise Paré [AP-HP], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Universitaire [Grenoble] (CHU), Institut Mutualiste de Montsouris (IMM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Rouen, Normandie Université (NU), CHU Bordeaux [Bordeaux], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Marseille, Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, CHU Lille, Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires (RNMCD - U1011), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Henri Mondor [Créteil], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD)
Subjects: medicine.medical_specialty, Randomization, education, 030204 cardiovascular system & hematology, Cardiovascular Medicine, Transoesophageal echocardiography, transesophageal echoardiography, law.invention, Likert scale, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, 030202 anesthesiology, law, Internal medicine, medicine, Methods, Diseases of the circulatory (Cardiovascular) system, Simulation based, Simulation, business.industry, 3. Good health, Test (assessment), Multicenter study, RC666-701, Cardiology, residents, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Cardiology and Cardiovascular Medicine, business, medical education, Educational program, human activities, simulation-based, randomized study
Abstract: Introduction: Simulation-based training in transesophageal echocardiography (TEE) seems promising. However, data are limited to non-randomized or single-center studies. To assess the impact of simulation-based vs. traditional teaching on TEE knowledge and performance for medical residents in cardiology.Materials and Methods: Nationwide prospective randomized multicenter study involving 43 centers throughout France allowing for the inclusion of >70% of all French cardiology residents. All cardiology residents naive from TEE will be included. Randomization with stratification by center will allocate residents to either a control group receiving theoretical knowledge by e-learning only, or to an intervention group receiving two simulation-based training sessions on a TEE simulator in addition.Results: All residents will undergo both a theoretical test (0–100 points) and a practical test on a TEE simulator (0–100 points) before and 3 months after the training. Satisfaction will be assessed by a 5-points Likert scale. The primary outcomes will be to compare the scores in the final theoretical and practical tests between the two groups, 3 months after the completion of the training.Conclusion: Data regarding simulation-based learning in TEE are limited to non-randomized or single-center studies. The randomized multicenter SIMULATOR study will assess the impact of simulation-based vs. traditional teaching on TEE knowledge and performance for medical residents in cardiology, and whether such an educational program should be proposed in first line for TEE teaching.
Published: 2021

134. Azoles susceptibility profiles of more than 9,000 clinical yeast isolates belonging to 40 common and rare species

Author: Olivier Lortholary, Françoise Dromer, Stéphane Bretagne, Marie Desnos-Ollivier, Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Paris Cité (UPCité), Institut Pasteur and Santé Publique France., Members of the French Mycoses Study group who contributed to the data are in alphabetical order of the cities, all the French microbiologists and mycologists who sent isolates for characterization of unusual antifungal susceptibility profiles or to contribute to the ongoing surveillance program on the epidemiology of invasive fungal infections in France (YEASTS and RESSIF programs): N. Brieu (CH Aix), T. Chouaki, C. Damiani, A. Totet (CHU Amiens, J. P. Bouchara, M. Pihet (CHU Angers), S. Bland (CH Annecy), V. Blanc (CH Antibes), S. Branger (CH Avignon), A. P. Bellanger, L. Million (CHU Besançon), C. Plassart (CH Beauvais), I. Poilane (hôpital Jean Verdier, Bondy), I. Accoceberry, L. Delhaes, F. Gabriel (CH Bordeaux), A. L. Roux, V. Sivadon-Tardy (hôpital Ambroise Paré, Boulogne Billancourt), F. Laurent (CH, Bourg en Bresse), S. Legal, E. Moalic, G. Nevez, D. Quinio (CHU Brest), M. Cariou (CH Bretagne Sud), J. Bonhomme (CHU, Caen), B. Podac (CH, Chalon sur Saône), S. Lechatch (CH, Charleville-Mézières), C. Soler (hopital d’Instruction des armées, Clamart), P. Poirier, C. Nourrisson (CHU, Clermont Ferrand), O. Augereau (CH, Colmar), N. Fauchet (CHIC, Créteil), F. Dalles (CHU, Dijon), P. Cahen (CMC, Foch), N. Desbois, C. Miossec (CHU, Fort de France), J. L. Hermann (hôpital Raymond Poincaré, Garches), M. Cornet, D. Maubon, H. Pelloux (CHU, Grenoble), M. Nicolas (CHU,Guadeloupe), C. Aznar, D. Blanchet, J. F. Carod, M. Demar, (CHU, Guyane), A. Angoulvant (hôpital Bicêtre, le Kremlin Bicêtre), C. Ciupek (CH, Le Mans), A. Gigandon (hôpital Marie Lannelongue, Le Plessis Robinson), B. Bouteille (CH Limoges), E. Frealle, B. Sendid (CHU Lille), D. Dupont, J. Menotti, F. Persat, M. Wallon (CHU, Lyon), C. Cassagne, S. Ranque (CHU, Marseille), T. Benoit-Cattin, L. Collet (CH Mayotte), A. Fiacre (CH Meaux), N. Bourgeois, L. Lachaud (CHU, Montpellier), M. Machouart (CHU, Nancy), P. Lepape, F. Morio (CHU, Nantes), O. Moquet (CH, Nevers), S. Lefrançois (hôpital Américain, Neuilly), M. Sasso (CHU, Nimes), F. Reibel (GH, Nord-Essone), M. Gari-Toussaint, L. Hasseine (CHU Nice), L. Bret, D. Poisson (CHR Orléans), S. Brun (hôpital Avicenne, Paris), C. Bonnal, S. Houze (hôpital Bichat, Paris), A. Paugam (hôpital Cochin, Paris), E. Dannaoui (HEGP, Paris), N. Ait-Ammar, F. Botterel, R. Chouk (CHU Henri Mondor, Paris), M. E. Bougnoux, E. Sitterle (hôpital Necker, Paris), A. Fekkar, R. Piarroux (hôpital Pitié Salpêtrière, Paris), J. Guitard, C. Hennequin (hôpital St Antoine, Paris), M. Gits-Muselli, S. Hamane (hôpital Saint Louis, Paris), S. Bonacorsi, P. Mariani (hôpital Robert Debré, Paris), D. Moissenet (hôpital Trousseau, Paris), A. Minoza, E. Perraud, M. H. Rodier (CHU Poitiers), G. Colonna (CH, Porto Vecchio), D. Toubas (CHU Reims), J. P. Gangneux, F. Robert-Gangneux (CHU Rennes), O. Belmonte, G. Hoarau, M. C. Jaffar Bandjee, J. Jaubert, S. Picot, N. Traversier (CHU Réunion), L. Favennec, G. Gargala (CHU, Rouen), C. Tournus (CH, St Denis), H. Raberin (CHU, St Etienne), V. Letscher Bru (CHU, Strasbourg), S. Cassaing (CHU, Toulouse), P. Patoz (CH Tourcoing), E. Bailly, G. Desoubeaux (CHU Tours), F. Moreau (CH Troyes), P. Munier (CH Valence), E. Mazars (CH Valenciennes), O. Eloy (CH Versailles), E. Chachaty (Institut Gustave Roussy, Villejuif), and members of the NRCMA (Institut Pasteur, Paris): A. Boullié, C. Gautier, V. Geolier, C. Blanc, D. Hoinard and D. Raoux-Barbot for technical help, and K. Boukris-Sitbon, F. Lanternier, A. Alanio, D. Garcia-Hermoso for their expertise and contribution to the surveillance programs., Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], and Université de Paris (UP)
Subjects: Serotype, Azoles, Antifungal Agents, Microbial Sensitivity Tests, Candida parapsilosis, Rhodotorula mucilaginosa, Pichia, Microbiology, Candida tropicalis, 03 medical and health sciences, 0302 clinical medicine, Drug Resistance, Fungal, Pharmacology (medical), 030212 general & internal medicine, Candida albicans, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Pharmacology, chemistry.chemical_classification, 0303 health sciences, biology, Candida glabrata, 030306 microbiology, Broth microdilution, Rhodotorula, biology.organism_classification, 3. Good health, Infectious Diseases, chemistry, Susceptibility, Saccharomycetales, Azole, France
Abstract: Invasive yeast infections represent a major global public health issue, and only few antifungal agents are available. Azoles are one of the classes of antifungals used for treatment of invasive candidiasis. The determination of antifungal susceptibility profiles using standardized methods is important to identify resistant isolates and to uncover the potential emergence of intrinsically resistant species. Here, we report data on 9,319 clinical isolates belonging to 40 pathogenic yeast species recovered in France over 17 years. The antifungal susceptibility profiles were all determined at the National Reference Center for Invasive Mycoses and Antifungals based on the EUCAST broth microdilution method. The centralized collection and analysis allowed us to describe the trends of azole susceptibility of isolates belonging to common species, confirming the high susceptibility for Candida albicans (n = 3,295), Candida tropicalis (n = 641), and Candida parapsilosis (n = 820) and decreased susceptibility for Candida glabrata (n = 1,274) and Pichia kudriavzevii (n = 343). These profiles also provide interesting data concerning azole susceptibility of Cryptococcus neoformans species complex, showing comparable MIC distributions for the three species but lower MIC(50)s and MIC(90)s for serotype D (n = 208) compared to serotype A (n = 949) and AD hybrids (n = 177). Finally, these data provide useful information for rare and/or emerging species, such as Clavispora lusitaniae (n = 221), Saprochaete clavata (n = 184), Meyerozyma guilliermondii complex (n = 150), Candida haemulonii complex (n = 87), Rhodotorula mucilaginosa (n = 55), and Wickerhamomyces anomalus (n = 36).
Published: 2021

135. Quantitative Brain Sodium MRI Depicts Corticospinal Impairment in Amyotrophic Lateral Sclerosis

Author: Lothar R. Schad, Shahram Attarian, Wafaa Zaaraoui, Aude-Marie Grapperon, Maxime Guye, Jean-Philippe Ranjeva, Ben Ridley, Sylviane Confort-Gouny, Etienne Fortanier, Annie Verschueren, Adil Maarouf, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS), Centre de référence des maladies rares neuromusculaires, Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, AP-HM, Pôle d'imagerie médicale, Hôpital de la Timone, CEMEREM, Marseille, France, University of Heidelberg, Medical Faculty, Centre de référence des maladies neuromusculaires et de la SLA, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), and Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, medicine.medical_treatment, Sodium, Pyramidal Tracts, chemistry.chemical_element, Corpus callosum, computer.software_genre, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Voxel, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Amyotrophic lateral sclerosis, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Aged, business.industry, Amyotrophic Lateral Sclerosis, Brain, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Transcranial magnetic stimulation, chemistry, Evaluation Studies as Topic, 030220 oncology & carcinogenesis, Sodium MRI, Cardiology, Female, Sodium Isotopes, business, computer
Abstract: Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that mainly affects the upper and lower motor neurons. Recent sodium (23Na) MRI studies have shown that abnormal sodium concentration is related to neuronal suffering in neurodegenerative conditions. Purpose To use 23Na MRI to investigate abnormal sodium concentrations and map their distribution in the brains of study participants with ALS as compared with healthy control subjects. Materials and Methods Twenty-seven participants with ALS (mean age, 54 years ± 10 [standard deviation], eight women) and 30 healthy control subjects (mean age, 50 years ± 10; 16 women) were prospectively recruited between September 2015 and October 2017 and were examined by using conventional proton MRI and sodium MRI at 3 T. Voxel-based statistical mapping was used to compare quantitative whole-brain total sodium concentration (TSC) maps in participants with ALS with those in control subjects and to localize regions of abnormal elevated TSC. Potential overlap of abnormal elevated TSC with regions of atrophy as detected with 1H MRI also was investigated. Results Voxel-based statistical mapping analyses revealed higher sodium concentration in motor regions (bilateral precentral gyri, corticospinal tracts, and the corpus callosum) of participants with ALS (two-sample t test, P < .005; age and sex as covariates). In these regions, mean TSC was higher in participants with ALS (mean, 45.6 mmol/L wet tissue ± 3.2) than in control subjects (mean, 41.8 mmol/L wet tissue ± 2.7; P < .001; Cohen d = 1.28). Brain regions showing higher TSC represented a volume of 15.4 cm3 that did not overlap with gray matter atrophy occupying a volume of 16.9 cm3. Elevated TSC correlated moderately with corticospinal conduction failure assessed with transcranial magnetic stimulation in the right upper limb (Spearman ρ = -0.57; 95% confidence interval: -0.78, -0.16; P = .005; n = 23). Conclusion Quantitative 23Na MRI is sensitive to alterations of brain sodium homeostasis within disease-relevant regions in patients with amyotrophic lateral sclerosis (ALS). This supports further investigation of abnormal sodium concentration as a potential marker of neurodegenerative processes in patients with ALS that could be used as a secondary endpoint in clinical trials. © RSNA, 2019 Online supplemental material is available for this article.
Published: 2019

136. Complement Gene Variants and Shiga Toxin-Producing Escherichia coli-Associated Hemolytic Uremic Syndrome

Author: Corinne Alberti, Paula Vieira-Martins, Véronique Frémeaux-Bacchi, Anne-Laure Sellier-Leclerc, Patricia Mariani, Tim Ulinski, Georges Deschênes, Sophie Limou, Annie Lahoche, Gwenaelle Roussey, François Nobili, Mathilde Cailliez, Brigitte Llanas, Theresa Kwon, Robert Novo, François-Xavier Weill, Chantal Loirat, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Translational ImmunoGenetic in AutoImmunity and Transplantation (Team 5 - U1064 Inserm - CRTI), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de Néphrologie pédiatrique [Hôpital Robert Debré, Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Bordeaux [Bordeaux], Service de pédiatrie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Marseille, Service de néphrologie et pédiatrie générale [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Hopital Robert Debre, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence - National Reference Center Escherichia coli, Shigella et Salmonella (CNR-ESS), Institut Pasteur [Paris], Service de Microbiologie [Hôpital Robert Debré - APHP], Centre National de Référence associé Escherichia coli [Hôpital Robert Debré - APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by grants from the Programme Hospitalier de Recherche Clinique (AOR 09 077 and AOM08198, to V.F.-B., A.-L.S.-L., and C.L.), by the European Union FP7 grant 2012-305608 (to V.F.-B., EURenOmics), the Fondation du rein (FRM Prix 2012 FDR, to V.F.-B.), and the Association pour l’Information et la Recherche dans les maladies Rénales génétiques (AIRG France)., European Project: 305608,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,EURENOMICS(2012), École Pratique des Hautes Études (EPHE), CHU Trousseau [APHP], Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris] (IP), AP-HP Hôpital universitaire Robert-Debré [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de Référence associé Escherichia coli [Hôpital Robert Debré - APHP]
Subjects: Genotype, Epidemiology, Complement, 030232 urology & nephrology, Critical Care and Intensive Care Medicine, Shiga Toxin, Membrane Cofactor Protein, Kidney Failure, 03 medical and health sciences, 0302 clinical medicine, Gene Frequency, Atypical hemolytic uremic syndrome, Escherichia coli, Medicine, human, Chronic, Shiga toxin-hemolytic uremic syndrome, pathogenic variants, Complement Activation, Allele frequency, Atypical Hemolytic Uremic Syndrome, 030304 developmental biology, 0303 health sciences, Transplantation, biology, C5b-9, CD46, business.industry, Shiga toxin producing E coli-hemolytic uremic syndrome, complement factor H, High-Throughput Nucleotide Sequencing, Shiga toxin, CD46 protein, Complement System Proteins, medicine.disease, 3. Good health, Complement system, Minor allele frequency, complement gene variant, Nephrology, Factor H, Immunology, hemolytic uremic syndrome, biology.protein, business, Genetic Background, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; BACKGROUND AND OBJECTIVES: Inherited complement hyperactivation is critical for the pathogenesis of atypical hemolytic uremic syndrome (HUS) but undetermined in postdiarrheal HUS. Our aim was to investigate complement activation and variants of complement genes, and their association with disease severity in children with Shiga toxin-associated HUS.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Determination of complement biomarkers levels and next-generation sequencing for the six susceptibility genes for atypical HUS were performed in 108 children with a clinical diagnosis of post-diarrheal HUS (75 Shiga toxin-positive, and 33 Shiga toxin-negative) and 80 French controls. As an independent control cohort, we analyzed the genotypes in 503 European individuals from the 1000 Genomes Project.RESULTS: During the acute phase of HUS, plasma levels of C3 and sC5b-9 were increased, and half of patients had decreased membrane cofactor protein expression, which normalized after 2 weeks. Variants with minor allele frequency
Published: 2019

137. Targeted-Capture Next-Generation Sequencing in Diagnosis Approach of Pediatric Cholestasis

Author: Marion Almes, Anne Spraul, Mathias Ruiz, Muriel Girard, Bertrand Roquelaure, Nolwenn Laborde, Fréderic Gottrand, Anne Turquet, Thierry Lamireau, Alain Dabadie, Marjorie Bonneton, Alice Thebaut, Babara Rohmer, Florence Lacaille, Pierre Broué, Alexandre Fabre, Karine Mention-Mulliez, Jérôme Bouligand, Emmanuel Jacquemin, Emmanuel Gonzales, Centre de référence des Maladies Vasculaires du Foie [Paris] (FILFOIE), Hôpital Bicêtre, Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hepatinov (DHU), Université Paris-Sud - Paris 11 (UP11)-Centre Hépato-Biliaire Paul Brousse, Hospices Civils de Lyon (HCL), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Marseille, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Lille, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], CHU Bordeaux [Bordeaux], Hôpital Sud [CHU Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique, and Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)
Subjects: Genetic cholestasis, genetic cholestasis, children, NGS, neonatal sclerosing cholangitis, PFIC, Alagille syndrome, transient neonatal cholestasis, Clinical Biochemistry, Neonatal sclerosing cholangitis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Transient neonatal cholestasis, Children
Abstract: International audience; BACKGROUND: Cholestasis is a frequent and severe condition during childhood. Genetic cholestatic diseases represent up to 25% of pediatric cholestasis. Molecular analysis by targeted-capture next generation sequencing (NGS) has recently emerged as an efficient diagnostic tool. The objective of this study is to evaluate the use of NGS in children with cholestasis. METHODS: Children presenting cholestasis were included between 2015 and 2020. Molecular sequencing was performed by targeted capture of a panel of 34 genes involved in cholestasis and jaundice. Patients were classified into three categories: certain diagnosis; suggested diagnosis (when genotype was consistent with phenotype for conditions without any available OMIM or ORPHANET-number); uncertain diagnosis (when clinical and para-clinical findings were not consistent enough with molecular findings). RESULTS: A certain diagnosis was established in 169 patients among the 602 included (28.1%). Molecular studies led to a suggested diagnosis in 40 patients (6.6%) and to an uncertain diagnosis in 21 patients (3.5%). In 372 children (61.7%), no molecular defect was identified. CONCLUSIONS: NGS is a useful diagnostic tool in pediatric cholestasis, providing a certain diagnosis in 28.1% of the patients included in this study. In the remaining patients, especially those with variants of uncertain significance, the imputability of the variants requires further investigations.
Published: 2022

138. Association of patterns of care, prognostic factors, and use of radiotherapy–temozolomide therapy with survival in patients with newly diagnosed glioblastoma: a French national population-based study

Author: Faiza Bessaoud, Johan Pallud, Sonia Zouaoui, Valérie Rigau, Hugues Duffau, Adeline Riondel, Brigitte Trétarre, Pascale Fabbro-Peray, Emmanuel Mandonnet, Luc Taillandier, M. Charissoux, Amélie Darlix, Dominique Figarella-Branger, Hélène Mathieu-Daudé, L. Bauchet, Elodie Sorbets, Fabienne Bauchet, Michel Fabbro, Aymeric Amelot, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut du Cancer de Montpellier (ICM), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'ophthalmologie [CHU Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Hôpital Lariboisière-Fernand-Widal [APHP], CHU Marseille, Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Gui de Chauliac [Montpellier], Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)
Subjects: Male, Oncology, Cancer Research, Databases, Factual, medicine.medical_treatment, 0302 clinical medicine, Risk of mortality, Practice Patterns, Physicians', Aged, 80 and over, education.field_of_study, Brain Neoplasms, Middle Aged, Prognosis, Combined Modality Therapy, 3. Good health, Survival Rate, Neurology, 030220 oncology & carcinogenesis, Female, France, Neurosurgery, medicine.drug, Cohort study, Adult, medicine.medical_specialty, Population, 03 medical and health sciences, Internal medicine, Neuro-oncology, Temozolomide, medicine, Humans, education, Antineoplastic Agents, Alkylating, Population-based study, Aged, business.industry, Clinical epidemiology, Confidence interval, Radiation therapy, Concomitant, Clinical Study, Neurology (clinical), Glioblastoma, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: Background Glioblastoma is the most frequent primary malignant brain tumor. In daily practice and at whole country level, oncological care management for glioblastoma patients is not completely known. Objectives To describe oncological patterns of care, prognostic factors, and survival for all patients in France with newly-diagnosed and histologically confirmed glioblastoma, and evaluate the impact of extended temozolomide use at the population level. Methods Nationwide population-based cohort study including all patients with newly-diagnosed and histologically confirmed glioblastoma in France in 2008 and followed until 2015. Results Data from 2053 glioblastoma patients were analyzed (male/female ratio 1.5, median age 64 years). Median overall survival (OS) was 11.2 [95% confidence interval (CI) 10.7–11.9] months. The first-line therapy and corresponding median survival (MS, in months) were: 13% did not receive any oncological treatment (biopsy only) (MS = 1.8, 95% CI 1.6–2.1), 27% received treatment without the combination of radiotherapy (RT)–temozolomide (MS = 5.9, 95% CI 5.5–6.6), 60% received treatment including the initiation of the concomitant phase of RT–temozolomide (MS = 16.4, 95% CI 15.2–17.4) whom 44% of patients initiated the temozolomide adjuvant phase (MS = 18.9, 95% CI 18.0–19.8). Only 22% patients received 6 cycles or more of adjuvant temozolomide (MS = 25.5, 95% CI 24.0–28.3). The multivariate analysis showed that the risk of mortality was significantly higher for the non-progressive patients who stopped at 6 cycles (standard protocol) than those who continued the treatment, hazard ratio = 1.5 (95% CI 1.2–1.9). Conclusion In non-progressive patients, prolonging the adjuvant temozolomide beyond 6 cycles may improve OS. Electronic supplementary material The online version of this article (10.1007/s11060-018-03065-z) contains supplementary material, which is available to authorized users.
Published: 2018

139. Valeurs de référence du valproate de sodium (CAS n°1069-66-5). Valeurs toxicologiques de référence par voie orale et inhalation, valeurs limites d’exposition professionnelle et valeurs biologiques: Avis de l’Anses. Rapport d’expertise collective

Author: Elisabeth Elefant, Marie-Chantal Canivenc Lavier, François Clinard, Dany Chevalier, Raphaël Delépée, Jean-Baptiste FINI, Bénédicte Lelièvre, Frédéric Lirussi, Dominique Masset, Jean-Ulrich Mullot, Julien Roussel, Irène Sari-Minodier, Jeanne Stadler, Jérôme Thireau, Isabelle Manière, Aurélie Mathieu-Huart, Marion Keirsbulck, Amandine Paillat, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Université de Lille, Université de Caen Normandie (UNICAEN), Normandie Université (NU), Physiologie moléculaire et adaptation (PhyMA), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), UFR des Sciences de Santé (Université de Bourgogne), Université de Bourgogne (UB), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Agence nationale de sécurité du médicament et des produits de santé [Saint-Denis] (ANSM), Laboratoire d'Analyses de Surveillance et d'Expertise de la Marine (LASEM), Service de Santé des Armées, Université de Montpellier (UM), CHU Marseille, Consultante indépendante, Centre National de la Recherche Scientifique (CNRS), Direction de l'Evaluation des Risques (DER), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), and Anses
Subjects: Valeur toxicologique de référence, Indicateur biologique d’exposition, Expertise, TRV, Metrology, Lieux de travail, VTR, Biomarkers of exposure, Valeurs limites biologiques, VLEP, Sodium valproate, Measurement methods, Valeur de référence, Air des lieux de travail, Valproic acid, Valproate de sodium, Workplaces, Valproate, Méthodes de mesure, biological limit values, Workplace air, OEL, Toxicological reference value, Occupational, Métrologie, Milieu professionnel, Occupational exposure limit, Biological indicators of exposure, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Expert assessment, Limit values, Valeurs limites, MESH: Valproic Acid, Reference value, Acide valproïque
Abstract: Le site de Sanofi situé à Mourenx, dans le bassin industriel de Lacq (64), produit un médicament antiépileptique, la Dépakine®, dont le principe actif est le valproate de sodium (VPS). Ce site est une installation classée pour la protection de l’environnement (ICPE) soumise à autorisation au titre de l’article L.511-1 et suivants du Code de l’environnement. Les rejets dans l’environnement d’une telle installation sont encadrés par des limites établies sur la base d’une évaluation quantitative des risques sanitaires (EQRS). En 2017, Sanofi Chimie a réalisé une évaluation de l’impact sur la santé et l’environnement des rejets atmosphériques de valproate, en utilisant des valeurs toxicologiques de référence (VTR) à seuil par voie orale, cutanée et respiratoire proposées par le bureau d’étude CEHTRA (Consultancy for Environmental & Human Toxicology and Risk Assessment). Parmi les différentes VTR proposées par CEHTRA, Sanofi a utilisé les VTR fondées sur des effets tératogènes. L’EQRS conduite par la société AECOM pour le compte de Sanofi, en vue d’estimer les risques pour les riverains et les professionnels travaillant à proximité du site, a conclu que « les risques sanitaires liés aux rejets actuels et passés de valproate [étaient] inférieurs aux valeurs de référence » proposées par CEHTRA. L’Anses a été saisie le 29 juin 2018 par la DGS et la DGPR afin de mener, en urgence, une analyse critique des VTR du valproate élaborées pour le compte de Sanofi et utilisées dans le cadre de cette EQRS. Dans son avis du 12 juillet 2018, l’Anses n’a pas remis en cause le choix de construire une VTR à seuil mais n’a pas retenu les VTR élaborées par les deux bureaux d’études, EQUITOX (2015) et CEHTRA (2017), à partir des données animales et/ou humaines car de nombreuses données chez l’Homme disponibles dans la littérature n’avaient pas été prises en compte (Anses, 2018). Dans ce contexte, et au titre de la sécurité des professionnels exposés au valproate, une campagne de mesures de la concentration d’acide valproïque (VPA) dans le sang des employés de l’usine a été organisée par le service de santé au travail de l’entreprise du 27 novembre à la mi-décembre 2018. Le groupe d'alerte en santé travail (GAST) de Nouvelle-Aquitaine a été associé au suivi de cette campagne. Pour l’analyse de cette campagne de mesures, l’entreprise Sanofi s’est référée à une valeur biologique repère dans le sang de 5 mg.L-1. Ainsi, la DGT, la DGS et la DGPR ont saisi l’Anses, le 5 avril 2019, pour mener, en urgence, une analyse critique de la valeur biologique utilisée comme repère par Sanofi pour évaluer l’imprégnation de ses travailleurs. Au vu des données disponibles, le choix du dosage du valproate dans le sang n’a pas été remis en cause. Néanmoins, au regard de la cinétique d’élimination plasmatique de cette substance et de l’existence de métabolites urinaires, il n’a pas été exclu qu’un autre biomarqueur puisse être un meilleur témoin de l’exposition agrégée sur une période plus longue. Concernant le calcul de la valeur limite biologique (VLB), l’approche basée sur la dose thérapeutique est à privilégier mais la dose thérapeutique de 1200 mg.j-1 retenue pour le calcul de la VLB est critiquable compte tenu des données actuellement disponibles. En effet, des effets indésirables, notamment reprotoxiques, pourraient être observés à des doses inférieures à 1200 mg.j-1. Par ailleurs, plusieurs incohérences ou un manque de justification de certains choix ont été relevés lors du calcul de VLB, en particulier au niveau de l’application des facteurs d’incertitude/de protection. Par conséquent, la VLB de 5 mg.L-1 utilisée par Sanofi n’a pas été retenue. Enfin, ne disposant pas de suffisamment d’informations, il n’a pas été possible d’apporter un regard critique et de se prononcer sur la méthode d’analyse et les modalités de prélèvement. L’Anses a, par conséquent, recommandé : ‐ de réaliser une revue approfondie de la littérature prenant en compte les données les plus récentes, en particulier chez l’Homme ; ‐ d’évaluer de manière approfondie la possibilité de recommander des valeurs de référence pouvant être utilisées pour la surveillance biologique des expositions professionnelles au valproate (Anses, 2019). Au regard des différents éléments, l’Anses a été saisie le 28 septembre 2018 par la DGS et la DGPR pour élaborer une VTR chronique par inhalation pour le valproate de sodium, puis en avril 2019 par la DGT, la DGS et la DGPR pour définir des valeurs de référence pouvant être utilisées pour la surveillance des expositions professionnelles au valproate.
Published: 2021

140. Current results of left gonadal vein transposition to treat nutcracker syndrome

Author: Adrien Kaladji, Wilfried Bertho, Anaïs Debucquois, Olivier Hartung, Lucie Salomon du Mont, Simon Rinckenbach, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Marseille, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Jonchère, Laurent
Subjects: Adult, Male, Renal Nutcracker Syndrome, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Pelvic congestion syndrome, Inferior vena cava, Veins, 03 medical and health sciences, Nutcracker syndrome, Left gonadal vein transposition, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine, Back pain, Humans, 030212 general & internal medicine, Vein, Gonads, Aged, Retrospective Studies, business.industry, Pelvic pain, Middle Aged, medicine.disease, Thrombosis, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Surgery, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Treatment Outcome, medicine.vein, Female, medicine.symptom, Gonadal vein, Cardiology and Cardiovascular Medicine, business, Vascular Surgical Procedures
Abstract: International audience; OBJECTIVE: Nutcracker syndrome can cause disabling chronic pain requiring surgical intervention. At present, data describing a straightforward management approach are lacking. Transposition of the left gonadal vein is one of the surgical therapeutic alternatives. The aim of the present study was to describe our clinical results with gonadal vein transposition. METHODS: All 11 patients from three centers who had undergone left gonadal vein transposition for nutcracker syndrome from 2016 to 2019 were retrospectively included. The surgical cases were mainly selected according to the morphologic criteria of the left gonadal vein. The diameter and length dictated the type of approach (laparotomy or retroperitoneal) and the transposition level. A minimally invasive retroperitoneal approach was preferred. Pain was assessed using a numeric rating scale. RESULTS: We included 11 patients (10 women) with a median age of 35 years (range, 25-69). Preoperative computed tomography angiography showed anterior nutcracker syndrome in 10 patients (91%). All 11 patients had experienced lower back and/or pelvic pain, which was associated with pelvic congestion syndrome in 6 patients (55%) and hematuria in 5 patients (45%). The median preoperative numeric rating scale score for pain was 7.0 (range, 3.5-10.0) and 6.0 (range, 3.5-8.0) for lower back pain and pelvic pain, respectively. At the level of the iliac vein crossing (external or common), the median diameter of the left gonadal vein was 7.87 mm (range, 6.45-11.28). The left gonadal vein was transposed to the inferior vena cava in one case (9%), the left external iliac vein in five (45%), and the left common iliac vein in five cases (45%). The median in-hospital stay was 4 days (range, 2-20 days). Two early complications (18%) requiring surgical revision occurred: one of active bleeding and one hematoma. The median follow-up was 15 months (range, 6-44 months). The median postoperative pain score was 1.0 (range, 0.0-4.0) and 0.0 (range, 0.0-6.0) for lower back and pelvic pain, respectively. Incisional and/or neuropathic pain was noted, with a median score of 3.5 (range, 1.0-6.0) in seven patients (64%). Two late complications (18%) were observed: one case of thrombosis and one case of anastomotic stenosis. The hematuria had disappeared in all patients who had presented with it initially. CONCLUSIONS: Left gonadal vein transposition can be proposed as a first approach if the diameter of the left gonadal vein is sufficient to perform the anastomosis. It is an easily achievable, minimally invasive alternative that achieves satisfactory results without the use of foreign material.
Published: 2021

141. Assessing the experience of the quality of care of patients living with multiple sclerosis and their caregivers: the MusiCare Questionnaire

Author: Marc Debouverie, Jean Pelletier, Jérôme De Seze, Marie Elisabeth Cosson, Karine Baumstarck, Pierre Clavelou, Gilles Edan, Anderson Loundou, David Veillard, Sandrine Wiertlewski, Christophe Verny, Pascal Auquier, Karine Chauvin, CHU Pontchaillou [Rennes], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Strasbourg, CHU Clermont-Ferrand, CHU Marseille, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques, Ministère de la Santé, Fondation de France, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent
Subjects: medicine.medical_specialty, Psychometrics, [SDV]Life Sciences [q-bio], multiple sclerosis, External validity, 03 medical and health sciences, 0302 clinical medicine, quality of care, Internal consistency, Surveys and Questionnaires, Patient experience, Health care, medicine, Humans, 030212 general & internal medicine, Quality of care, validation, business.industry, patient experience, Multiple sclerosis, Reproducibility of Results, McDonald criteria, medicine.disease, caregiver experience, 3. Good health, [SDV] Life Sciences [q-bio], caregiver experience multiple sclerosis, Neurology, Caregivers, Physical therapy, Quality of Life, Item generation, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: International audience; Background and purpose - Patients with a chronic illness, such as multiple sclerosis (MS), and their natural caregivers have a specific experience of healthcare and health services. These experiences need to be assessed to evaluate the quality of care. Our objective was to develop a French-language questionnaire to evaluate the quality of care as experienced by MS patients and their natural caregivers. Methods - Eligible patients had been diagnosed with MS according to the McDonald criteria. Eligible caregivers were individuals designated by the patients. The MusiCare questionnaire was developed in two standard phases: (i) item generation, based on interviews with patients and caregivers; and (ii) validation, consisting of validity, reliability, external validity, reproducibility, and responsiveness measures. Results - In total, 1088 patients (n = 660) and caregivers (n = 488) were recruited. The initial 64-item version of MusiCare was administered to a random subsample (n = 748). The validation process generated a 35-item questionnaire. Internal consistency and scalability were satisfactory. Testing of the external validity revealed expected associations between MusiCare scores and sociodemographic and clinical data. The questionnaire showed good reproducibility and responsiveness. Conclusions - The availability of a reliable and validated French-language self-report questionnaire probing the experience of the quality of care for MS will allow the feedback of patients and caregivers to be incorporated into a continuous healthcare quality-improvement strategy.
Published: 2021

142. Spontaneous Reports of Serious Adverse Drug Reactions Resulting From Drug–Drug Interactions: An Analysis From the French Pharmacovigilance Database

Author: Louis, Létinier, Amandine, Ferreira, Alexandre, Marceron, Marina, Babin, Joëlle, Micallef, Ghada, Miremont-Salamé, Antoine, Pariente, Otten, Lisa, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Institut de Neurosciences des Systèmes (INS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)
Subjects: Pharmacology, hemorrhages, immune system diseases, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, pharmacovigilance, adverse drug reaction, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, virus diseases, spontaneous reporting, drug–drug interaction, antithrombotic agents, drug-drug interaction, Original Research
Abstract: International audience; Few data are available on the clinical impact of drug–drug interactions (DDIs). Most of the studies are limited to the analysis of exposure to potential DDI or the targeted impact of the combination of a few drugs or therapeutic classes. The analysis of adverse drug reaction (ADR) reports could be a mean to study generally the adverse effects identified due to a DDI. Our objective was to describe the characteristics of ADRs resulting from DDIs reported to the French Pharmacovigilance system and to identify the drugs most often implicated in these ADRs. Considering all ADR reports from January 01, 2012, to December 31, 2016, we identified all cases of ADR resulting from a DDI (DDI-ADRs). We then described these in terms of patients’ characteristics, ADR seriousness, drugs involved (two or more per case), and ADR type. Of the 4,027 reports relating to DDI-ADRs, 3,303 were related to serious ADRs. Patients with serious DDI-ADRs had a median age of 76 years (interquartile range: 63–84); 53% were male. Of all serious DDI-ADRs, 11% were life-threatening and 8% fatal. In 36% of cases, the DDI causing the ADR involved at least three drugs. Overall, 8,424 different drugs were mentioned in the 3,303 serious DDI-ADRs considered. Altogether, drugs from the “antithrombotic agents” subgroup were incriminated in 34% of serious DDI-ADRs. Antidepressants were the second most represented therapeutic/pharmacological subgroup (5% of serious DDI-ADRs). Among the 3,843 ADR types reported in the 3,303 serious DDI-ADRs considered, the most frequently represented were hemorrhage (40% clinical hemorrhage; 6% biological hemorrhage), renal failure (8%), pharmacokinetic alteration (5%), and cardiac arrhythmias (4%). Hemorrhagic accidents are still an important part of serious ADRs resulting from DDIs reported in France. The other clinical consequences of DDIs seem less well identified by pharmacovigilance. Moreover, more than one-third of serious DDI-ADRs involved at least three drugs.
Published: 2021

143. Anticoagulation prior to hospitalization is a potential protective factor for COVID-19: insight from a French multicenter cohort study

Author: Chocron, Richard, Galand, Vincent, Cellier, Joffrey, Gendron, Nicolas, Pommier, Thibaut, Bory, Olivier, Khider, Lina, Trimaille, Antonin, Goudot, Guillaume, Weizman, Orianne, Alsac, Jean Marc, Geneste, Laura, Schmeltz, Armand, Panagides, Vassili, Philippe, Aurélien, Marsou, Wassima, Ben Abdallah, Iannis, Deney, Antoine, El Batti, Salma, Attou, Sabir, Juvin, Philippe, Delmotte, Stephane, Messas, Emmanuel, Pezel, Théo, Planquette, Benjamin, Duceau, Baptiste, Gaussem, Pascale, Sutter, Willy, Sanchez, Olivier, Waldman, Victor, Diehl, Jean-Luc, Mirault, Tristan, Bonnet, Guillaume, Cohen, Ariel, Smadja, David M, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Université de Paris, Innovative Therapies in Haemostasis, Service d'Hématologie et Laboratoire de Recherches Biochirugicales (Fondation Carpentier), AH-H, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Hématologie et Laboratoire de Recherches Biochirugicales (Fondation Carpentier), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Strasbourg, Department of Cardiology [Ospedali del Tigullio], CHU Amiens-Picardie, CHU Marseille, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Toulouse [Toulouse], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Cardiologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), ANR-21-COVR-0017,SCHIZOVAC,Attitudes envers les vaccins et competence à consentir à la vaccination anti COVID-19 dans la schizophrénie(2021), and Jonchère, Laurent
Subjects: Male, Severity of Illness Index, Vascular Medicine, SARS‐CoV‐2, coagulopathy, COVID‐19, Early Medical Intervention, Thromboembolism, Humans, Hospital Mortality, Blood Coagulation, Original Research, [SDV.IB] Life Sciences [q-bio]/Bioengineering, SARS-CoV-2, anticoagulant, Anticoagulants, COVID-19, Middle Aged, Protective Factors, Prognosis, mortality, Hospitalization, Intensive Care Units, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Endothelium, Vascular, France, Mortality/Survival
Abstract: International audience; Background Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with thrombotic outcomes with coagulation and endothelial disorders. Based on that, several anticoagulation guidelines have been proposed. We aimed to determine whether anticoagulation therapy modifies the risk of developing severe COVID-19. Methods and Results Patients with COVID-19 initially admitted in medical wards of 24 French hospitals were included prospectively from February 26 to April 20, 2020. We used a Poisson regression model, Cox proportional hazard model, and matched propensity score to assess the effect of anticoagulation on outcomes (intensive care unit admission or in-hospital mortality). The study enrolled 2878 patients with COVID-19, among whom 382 (13.2%) were treated with oral anticoagulation therapy before hospitalization. After adjustment, anticoagulation therapy before hospitalization was associated with a better prognosis with an adjusted hazard ratio of 0.70 (95% CI, 0.55-0.88). Analyses performed using propensity score matching confirmed that anticoagulation therapy before hospitalization was associated with a better prognosis, with an adjusted hazard ratio of 0.43 (95% CI, 0.29-0.63) for intensive care unit admission and adjusted hazard ratio of 0.76 (95% CI, 0.61-0.98) for composite criteria intensive care unit admission or death. In contrast, therapeutic or prophylactic low- or high-dose anticoagulation started during hospitalization were not associated with any of the outcomes. Conclusions Anticoagulation therapy used before hospitalization in medical wards was associated with a better prognosis in contrast with anticoagulation initiated during hospitalization. Anticoagulation therapy introduced in early disease could better prevent COVID-19-associated coagulopathy and endotheliopathy, and lead to a better prognosis.
Published: 2021

144. Impact of abdominal or pelvic radiotherapy on disease activity in inflammatory bowel disease: a multicentre cohort study from the GETAID

Author: Broussard, Doriane, Riviere, Pauline, Bonnet, Joelle, Fotsing, Ginette, Amiot, Aurelien, Peyrin-Biroulet, Laurent, Rajca, Sylvie, Buisson, Anthony, Gilleta, Cyrielle, Pelletier, Anne-Laure, Serrero, Melanie, Bouguen, Guillaume, Altwegg, Romain, Hebuterne, Xavier, Nancey, Stephane, Fumery, Mathurin, Cadiot, Guillaume, Nahon, Stephane, Rahier, Jean-Francois, Gornet, Jean-Marc, Vendrely, Véronique, Laharie, David, CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire de Nancy (CHU Nancy), CHU Toulouse [Toulouse], CHU Marseille, CIC - Biotherapie - Marseille, Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Nord [CHU - APHM], Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Pontchaillou [Rennes], CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de l'Environnement Industriel et des Risques, Centre Hospitalier Universitaire de Reims (CHU Reims), Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie
Subjects: Cohort Studies, Crohn Disease, [SDV]Life Sciences [q-bio], Abdomen, Humans, Female, Middle Aged, Inflammatory Bowel Diseases, Retrospective Studies
Abstract: International audience; Background - Abdominal or pelvic radiotherapy in inflammatory bowel disease (IBD) patients raises concerns regarding the risk of worsening of underlying disease. Aim - To assess the impact of radiotherapy on IBD course. Methods - A retrospective multicentre study including IBD patients exposed to abdominal or pelvic irradiation was conducted, retrieving IBD activity by semester (6-month periods) before (from S-4 to S-1) and after (from S + 1 to S + 6) radiotherapy and IBD flare during follow-up. Results - Sixty-one patients (32 women, mean age 59 years), with 467 patient semesters of follow-up, treated for digestive (n = 31), urinary tract (n = 23) and gynaecological cancers (n = 7) were included. Rates of IBD activity per semester were, respectively, 21% (95% CI: 16-27) from S-4 to S-1; 12% (7-19) from S + 1 to S + 3 (P = 0.15 vs S-4 to S-1) and 16% (10-25) from S + 4 to S + 6 (P = 0.45 vs S-4 to S-1). With a median follow-up of 156 weeks (interquartile range: 82-365), rates of survival without IBD flare at 1 and 3 years after radiotherapy were 82.5% (73.2-93.0) and 70.6% (58.8-84.7). Moderate-to-severe acute radiotherapy-induced gut toxicity and the absence of concomitant chemotherapy were independently associated with an increased risk of flare. Conclusion - Most patients with non-active IBD can be safely treated with abdominal or pelvic radiotherapy. Patients having acute gut toxicity and those without concomitant chemotherapy should be more closely monitored in the post-radiotherapy period.
Published: 2021

145. Treatment of Idiopathic Pulmonary Fibrosis with Capsule or Tablet Formulations of Pirfenidone in the Real-Life French RaDiCo-ILD Cohort

Author: Cottin, Vincent, Guéguen, Sonia, Nunes, Hilario, Jouneau, Stéphane, Crestani, Bruno, Bonniaud, Philippe, Wemeau, Lidwine, Israël-Biet, Dominique, Reynaud-Gaubert, Martine, Gondouin, Anne, Cadranel, Jacques, Marchand-Adam, Sylvain, Chevereau, Marie, Dufaure-Garé, Isabelle, Amselem, Serge, Clément, Annick, Bergot, Emmanuel, Bourdin, Arnaud, Chenivesse, Cécile, Dalphin, Jean-Charles, Dromer, Claire, Gomez, Emmanuel, Hirschi, Sandrine, Montani, David, Prévot, Grégoire, Quetant, Sébastien, Valeyre, Dominique, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Lille, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Marseille, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), UF de Génétique moléculaire [CHU Trousseau], CHU Trousseau [APHP], Service de Pneumologie pédiatrique [CHU Trousseau], Centre de référence national pour les maladies respiratoires rares de l’enfant RespiRare [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], and the RaDiCo team: Emmanuel Bergot, Philippe Bonniaud, Arnaud Bourdin, Jacques Cadranel, Cécile Chenivesse, Vincent Cottin, Bruno Crestani, Jean-Charles Dalphin, Claire Dromer, Emmanuel Gomez, Sandrine Hirschi, Dominique Israël-Biet, Stéphane Jouneau, Sylvain Marchand-Adam, David Montani, Hilario Nunes, Grégoire Prévot, Sébastien Quetant, Martine Reynaud-Gaubert, Dominique Valeyre, Lidwine Wemeau, and MORNET, Dominique
Subjects: medicine.medical_specialty, Pyridones, [SDV]Life Sciences [q-bio], Population, Interstitial lung disease, Pirfenidone, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Cohort Studies, 03 medical and health sciences, Idiopathic pulmonary fibrosis, 0302 clinical medicine, Internal medicine, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Adverse effect, education, Capsule, ComputingMilieux_MISCELLANEOUS, education.field_of_study, business.industry, General Medicine, medicine.disease, Rash, Idiopathic Pulmonary Fibrosis, 3. Good health, Clinical trial, Treatment Outcome, 030228 respiratory system, Cohort, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, France, Antifibrotic, medicine.symptom, Tablet, Lung Diseases, Interstitial, business, Tablets, Cohort study, medicine.drug
Abstract: Auteur groupe collaboratif RaDiCo team; International audience; Introduction: Pirfenidone, an antifibrotic medication for idiopathic pulmonary fibrosis (IPF), is now available in France in two formulations: tablets since April 2018, and the initial capsules form. We conducted a cohort study to describe tolerance and acceptability of capsules and/or tablets of pirfenidone in patients with IPF.Methods: This study was nested within the French, non-randomized, multicenter RaDiCo-ILD (Rare Disease Cohort-Interstitial Lung Diseases). Included patients with IPF received at least one dose of pirfenidone tablets or capsules from July 2017 to June 2019 in three populations: the inclusion population (patients treated at least once with pirfenidone during the study period, n = 288); the potential switch population (patients treated with pirfenidone during the switch period starting April 2018, n = 256); the newly treated population (patients who initiated pirfenidone during the study period, n = 162). Each of those last two populations included three subgroups (tablets, capsules, and substitution).Results: In 288 patients treated, 162 newly initiated pirfenidone during the study period: there were no meaningful differences in the baseline characteristics with the 256 patients treated during the potential switch period. In the newly treated population, 30.3% started pirfenidone treatment with tablet formulation. In the potential switch population, 44.9% of patients shifted from capsule to tablet. Half of the patients shifted to tablet formulation within the first 10 months. The mean treatment duration was 21.5 months with a mean dose of 2106.7 mg/day; 46.5% of patients discontinued treatment, mainly because of adverse events. There were fewer discontinuations in the tablets and substitution subgroups than in the capsules-only subgroup. The most reported adverse event was skin rash (11.5%). No new adverse event was identified.Conclusions: This real-life cohort assessing the characteristics of the prescription of pirfenidone tablets and capsules suggests a good acceptability of the tablet formulation by patients with IPF.Trial registration: Clinical trial registered with www.clinicaltrials.gov (NCT04238871).
Published: 2021

146. Endoscopic management of anastomotic leak after esophageal or gastric resection for malignancy: a multicenter experience

Author: Rachel Hallit, Arthur Belle, Pierre Cattan, Jérémie Jacques, Marc Barthet, T. Barrioz, Aymeric Becq, Marine Camus, Mélanie Calmels, D. Goéré, Frédéric Prat, Maximilien Barret, Romain Coriat, Romain Legros, Stanislas Chaussade, Xavier Dray, Diane Lorenzo, U. Chaput, Jean-Michel Gonzalez, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Beaujon [AP-HP], CHU Marseille, CHU Limoges, and Centre hospitalier universitaire de Poitiers (CHU Poitiers)
Subjects: esophageal or gastric cancer, Leak, medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, anastomotic leak, [SDV.CAN]Life Sciences [q-bio]/Cancer, RC799-869, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Endoscopic management, Anastomosis, Malignancy, 03 medical and health sciences, 0302 clinical medicine, esophagogastric junction adenocarcinoma, Anastomotic leaks, self-expendable metallic stent, medicine, esophageal cancer, Esophagogastric junction, Gastric resection, endoscopic management, business.industry, double pigtail stent, gastric cancer, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Esophageal cancer, Diseases of the digestive system. Gastroenterology, medicine.disease, 3. Good health, Surgery, internal drainage, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, business
Abstract: Background: Most anastomotic leaks after surgical resection for esophageal or esophagogastric junction malignancies are treated endoscopically with esophageal stents. Internal drainage by double pigtail stents has been used for the endoscopic management of leaks following bariatric surgery, and recently introduced for anastomotic leaks after resections for malignancies. Our aim was to assess the overall efficacy of the endoscopic treatment for anastomotic leaks after esophageal or gastric resection for malignancies. Methods: We conducted a multicenter retrospective study in four digestive endoscopy tertiary referral centers in France. We included consecutive patients managed endoscopically for anastomotic leak following esophagectomy or gastrectomy for malignancies between January 2016 and December 2018. The primary outcome was the efficacy of the endoscopic management on leak closure. Results: Sixty-eight patients were included, among which 46 men and 22 women, with a mean ± SD age of 61 ± 11 years. Forty-four percent had an Ivor Lewis procedure, 16% a tri-incisional esophagectomy, and 40% a total gastrectomy. The median time between surgery and the diagnosis of leak was 9 (6–13) days. Endoscopic treatment was successful in 90% of the patients. The efficacy of internal drainage and esophageal stents was 95% and 77%, respectively ( p = 0.06). The mortality rate was 3%. The only predictive factor of successful endoscopic treatment was the initial use of internal drainage ( p = 0.002). Conclusion: Endoscopic management of early postoperative leak is successful in 90% of patients, preventing highly morbid surgical revisions. Internal endoscopic drainage should be considered as the first-line endoscopic treatment of anastomotic fistulas whenever technically feasible.
Published: 2021

147. Impact of Subthalamic Deep Brain Stimulation on Impulse Control Disorders in Parkinson's Disease: A Prospective Study

Author: Caroline Giordana, Ouhaid Lagha-Boukbiza, David Grabli, Agathe Vrillon, Eric Bardinet, Christine Tranchant, Chloé Laurencin, Alexandre Eusebio, Caroline Moreau, Anne-Sophie Rolland, Cécile Hubsch, Elodie Hainque, Béchir Jarraya, François Proust, Franck Durif, Mélissa Tir, Jean-Luc Houeto, Maeva Kyheng, Sophie Drapier, Paul Voulleminot, Mylène Meyer, M.D.N. Santin, Olivier Rascol, Mathieu Anheim, Jimmy Voirin, Matthieu Bereau, David Devos, Nicolas Auzou, Tiphaine Rouaud, Jean-Christophe Corvol, Solveig Montaut, David Maltête, Thomas Wirth, CHU Strasbourg, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Lille, CHU Pontchaillou [Rennes], CHU Clermont-Ferrand, CHU Marseille, Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Bordeaux [Bordeaux], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Hospices Civils de Lyon (HCL), CHU Rouen, Normandie Université (NU), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nancy (CHU Nancy), CHU Toulouse [Toulouse], Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Amiens-Picardie, Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), French Ministry of Health (PHRC National 2012), French network NS-Park, France Parkinson charity, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Lille Neurosciences & Cognition - U 1172 (LilNCog)
Subjects: 0301 basic medicine, medicine.medical_specialty, Deep brain stimulation, Parkinson's disease, Impulse control disorder, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Humans, Medicine, Apathy, Prospective Studies, Risk factor, Prospective cohort study, business.industry, Parkinson Disease, medicine.disease, STN functional territories, 3. Good health, deep brain stimulation, Disruptive, Impulse Control, and Conduct Disorders, Subthalamic nucleus, Treatment Outcome, 030104 developmental biology, Neurology, impulse control disorder, Cohort, Neurology (clinical), prognosis, medicine.symptom, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: International audience; Background Impact of subthalamic deep brain stimulation (DBS) on impulse control disorders (ICD) in Parkinson's disease (PD) remains controversial. Objectives The objectives of this study were to analyze the natural history of ICD between baseline and 1 year after subthalamic DBS in patients with PD and to identify predictive factors, taking into account the positions of the active contact and stimulation parameters. Methods We analyzed postoperative modifications of ICD based on the multicentric, prospective Predictive Factors and Subthalamic Stimulation in Parkinson's Disease cohort. ICD status and Ardouin Scale of Behaviour in PD were assessed at baseline and 1 year following subthalamic DBS. Location of active contacts within the 3 subthalamic nucleus functional territories was investigated. Results A total of 217 were patients included. Of the patients, 10.6% had ICD at baseline of which 95.6% improved at 1 year following subthalamic DBS; 3.6% of the patients experienced de novo ICD at 1 year following subthalamic DBS. Dopamine agonist dose reduction (from 309.8 to 109.3 mg) was the main driver of ICD regression (P= 0.05). Higher preoperative dyskinesias were associated with poorer ICD evolution (P= 0.04). Whereas baseline apathy was a risk factor of de novo ICD (P= 0.02), ICD improvement correlated with postoperative apathy (P= 0.004). Stimulation power and position of active contacts-mainly located within the sensorimotor part of the subthalamic nucleus-did not influence ICD. Conclusions This 1-year, postoperative follow-up study showed ICD regression and dopaminergic drug reduction with optimal position of the active contacts within the subthalamic nucleus. Whereas patients with PD with preoperative ICD were prone to postoperative apathy, we also showed that those with preoperative apathy had a higher risk to experience postoperative de novo ICD, further highlighting the meaningful influence of postoperative management of dopaminergic medication on outcome and the continuum between apathy and ICD. (c) 2020 International Parkinson and Movement Disorder Society
Published: 2021

148. Atypical thrombosis associated with VaxZevria (R) (AstraZeneca) vaccine: Data from the French Network of Regional Pharmacovigilance Centres

Author: Anthony Bron, Joëlle Micallef, Nathalie Massy, Thomas Geeraerts, Thierry Vial, Francesco Salvo, Hugo Laujin, Mariette Baud, Sophie Liabeuf, Marie Blanche Valnet-Rabier, Marie Girot, Céline Mounier, Antoine El Kaddissi, Antoine Pariente, Mehdi Benkebil, Justine Perez, Kamel Masmoudi, Jean François Albucher, Sophie Gautier, François Montastruc, Annie Pierre Jonville-Béra, Aurélie Grandvuillemin, Evelyne Massardier, Nicolas Raposo, Charlène Boulay, Valérie Gras-Champel, CHU Amiens-Picardie, Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Toulouse [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Agence nationale de sécurité du médicament et des produits de santé [Saint-Denis] (ANSM), CHU Rouen, Normandie Université (NU), Hôpital JeanMinjoz, CHU Lille, Toulouse Neuro Imaging Center (ToNIC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Roger Salengro [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Aix Marseille Université (AMU), CHU Marseille, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Centre régional de pharmacovigilance de Grenoble [CHU Grenoble], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), French Network of Pharmacovigilance Centres, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-21-CO17-0001,Vigi-Drugs COVID-19,Identification précoce du risque associé aux médicaments utilisés dans le cadre de COVID-19 : analyse des données mondiales de pharmacovigilance(2021), DESSAIVRE, Louise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3)
Subjects: 2019-20 coronavirus outbreak, Time Factors, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], Letter to Editor, Antiviral Agents, Pharmacovigilance, medicine, Adverse Drug Reaction Reporting Systems, Humans, Pharmacology (medical), Pandemics, ComputingMilieux_MISCELLANEOUS, Covid-19 vaccine, SARS-CoV-2, business.industry, COVID-19, VaxZevria®, medicine.disease, Atypical thrombosis, Thrombosis, Virology, [SDV] Life Sciences [q-bio], Anti-PF4 antibodies, France, business, Thrombopenia
Abstract: The current COVID-19 pandemic is an exceptional health situation including for drug use. As there was no known effective drug for COVID-19 at the beginning of the pandemic, different candidates were proposed. In this short article, we present the French public pharmacovigilance activities during this health crisis. Although COVID-19 is a confounding factor per se, owing to its potential for multi-organ damage including the heart and kidney, the quality of the transmitted data in adverse drug reaction reports, the timeliness of feedback from clinicians, and the real-time pharmacological and medical analysis by the French network of the regional pharmacovigilance centers made it possible to swiftly identify relevant safety signals. The French National Agency of Medicine was thus able to validate the data and convey their findings very early. This decentralized organization based on medical and pharmacological evaluation of case reports has proven to be efficient and responsive in this unique and challenging healthcare emergency.
Published: 2021

149. Republication de : Recommandations Formalisées d’Experts. Prise en charge de la patiente avec une pré-éclampsie sévère - RFE Communes Société Française d’Anesthésie-Réanimation (SFAR) - Collège National des Gynécologues et Obstétriciens Français (CGNOF)

Author: Bonnet, Marie-Pierre, Garnier, Marc, Keita, Hawa, Compère, Vincent, Arthuis, Chloé, Raia-Barjat, Tiphaine, Berveiller, Paul, Burey, Julien, Bouvet, Lionel, Bruyère, Marie, Castel, Adeline, Clouqueur, Elodie, Gonzalez Estevez, Max, Faitot, Valentina, Fischer, Catherine, Fuchs, Florent, Lecarpentier, Edouard, Le Gouez, Agnès, Rigouzzo, Agnès, Rossignol, Mathias, Simon, Emmanuel, Vial, Florence, Vivanti, Alexandre, Zieleskiewicz, Laurent, Sénat, Marie-Victoire, Schmitz, Thomas, Sentilhes, Loïc, Service d'anesthésie-réanimation [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Anesthésie réanimation [CHU Tenon], CHU Tenon [AP-HP], Service d'Anesthésie Réanimation [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Anesthésie et soins intensifs [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre hospitalier universitaire de Nantes (CHU Nantes), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Saint-Etienne, Service de gynécologie et obstétrique [CHI Poissy-Saint Germain], CHI Poissy-Saint-Germain, Biologie de la Reproduction, Environnement, Epigénétique & Développement (BREED), École nationale vétérinaire - Alfort (ENVA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hospices Civils de Lyon (HCL), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Pôle d'anesthésie Réanimation [CHU de Toulouse], CHU Toulouse [Toulouse], Centre Hospitalier Tourcoing, Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Anesthesiology, Intensive care and Perioperative medicine - Hautepierre Hospital, Strasbourg, Hôpital Cochin [AP-HP], Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Intercommunal de Créteil (CHIC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), AP-HP - Hôpital Antoine Béclère [Clamart], Département d’Anesthésie-Réanimation-SMUR [Hôpital Lariboisière], Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Marseille, Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Pôle d'Obstétrique Reproduction Gynécologie Centre Aliénor d'Aquitaine, Hôpital Pellegrin, Bordeaux, France., Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), École nationale vétérinaire d'Alfort (ENVA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU de Toulouse, Pole d'anesthésie Réanimation, Hôpital Paule de Viguier, Toulouse F-31059, France, Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), BREED, INRAE, Pôle Anesthésie Réanimation [CHU de Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], Neonatal morbidity, Severe pre-eclampsia, Guidelines, Maternal morbidity
Abstract: International audience; To provide national guidelines for the management of women with severe pre-eclampsia. Design: A consensus committee of 26 experts was formed. A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE(r)) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. The last SFAR and CNGOF guidelines on the management of women with severe pre-eclampsia were published in 2009. The literature is now sufficient for an update. The aim of this expert panel guidelines is to evaluate the impact of different aspects of the management of women with severe preeclampsia on maternal and neonatal morbidities separately. The experts studied questions within 7 domains. Each question was formulated according to the PICO (Patients Intervention Comparison Outcome) model and the evidence profiles were produced. An extensive literature review and recommendations were carried out and analysed according to the GRADE(r) methodology. The SFAR/CNGOF experts panel provided 25 recommendations: 8 have a high level of evidence (GRADE 1+/−), 9 have a moderate level of evidence (GRADE 2+/−), and for 7 recommendations, the GRADE method could not be applied, resulting in expert opinions. No recommendation was provided for 3 questions. After one scoring round, strong agreement was reached between the experts for all the recommendations. Conclusions: There was strong agreement among experts who made 25 recommendations to improve practices for the management of women with severe pre-eclampsia.
Published: 2021

150. Valve-in-valve transcatheter aortic valve implantation after failed surgically implanted aortic bioprosthesis versus native transcatheter aortic valve implantation for aortic stenosis: Data from a nationwide analysis

Author: Arnaud Bisson, Christophe Saint Etienne, Nicolas Jaussaud, Thomas Cuisset, Thierry Bourguignon, Alexis Theron, Julien Herbert, Frédéric Collart, Pierre Deharo, Laurent Fauchier, Thibaud Lacour, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Trousseau [Tours], CHU Marseille, Hôpital de la Timone [CHU - APHM] (TIMONE), Département de Cardiologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Éducation Éthique Santé EA 7505 (EES), Université de Tours (UT), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), CCSD, Accord Elsevier, and Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)
Subjects: Aortic valve, Male, medicine.medical_specialty, Time Factors, Databases, Factual, 030204 cardiovascular system & hematology, Risk Assessment, Transcatheter Aortic Valve Replacement, TAVI, 03 medical and health sciences, 0302 clinical medicine, Aortic bioprosthesis, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Risk Factors, Internal medicine, medicine, Humans, 030212 general & internal medicine, Myocardial infarction, Longitudinal Studies, Stroke, Aged, Retrospective Studies, Aged, 80 and over, Bioprosthesis, Heart Valve Prosthesis Implantation, business.industry, General Medicine, Odds ratio, Aortic Valve Stenosis, medicine.disease, Confidence interval, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Prosthesis Failure, Stenosis, medicine.anatomical_structure, Treatment Outcome, Heart failure, Aortic Valve, Heart Valve Prosthesis, Propensity score matching, Cardiology, Valve-in-valve, Female, France, Cardiology and Cardiovascular Medicine, business
Abstract: International audience; Background. - Valve-in-valve transcatheter aortic valve implantation (TAVI) has emerged as a treatment for aortic bioprosthesis failure in case of prohibitive risk for redo surgery. However, clinical evaluation of valve-in-valve TAVI remains limited by the number of patients analysed.Aim. - To evaluate outcomes of valve-in-valve TAVI compared with native aortic valve TAVI at a nationwide level in France.Methods. - Based on the French administrative hospital discharge database, the study collected information for all consecutive patients treated with TAVI for aortic stenosis or with isolated valve-in-valve TAVI for aortic bioprosthesis failure between 2010 and 2019. Propensity score matching was used for the analysis of outcomes.Results. - A total of 44,218 patients were found in the database. After matching on baseline characteristics, 2749 patients were analysed in each arm. At 30 days, no significant differences were observed regarding the occurrence of major clinical events (composite of cardiovascular mortality, all-cause stroke, myocardial infarction, major or life-threatening bleeding and conversion to open heart surgery) (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.68-1.01; P = 0.32). During follow-up (mean 516 days), the combined endpoint of cardiovascular death, all-cause stroke or rehospitalization for heart failure was not different between the valve-in-valve TAVI and native TAVI groups (RR 1.03, 95% CI 0.94-1.13; P = 1.00).Conclusion. - We observed that valve-in-valve TAVI was associated with good short- and long-term outcomes. No significant differences were observed compared with native valve TAVI regarding clinical follow-up. (C) 2020 Elsevier Masson SAS.
Published: 2021

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