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1. Cyclophosphamide added to glucocorticoids in acute exacerbation of idiopathic pulmonary fibrosis (EXAFIP): a randomised, double-blind, placebo-controlled, phase 3 trial

Author: Abdellatif Tazi, Aurélie Le Borgne-Krams, Marine Cachanado, Tabassome Simon, Sylvain Marchand-Adam, Morgane Didier, Lidwine Wemeau-Stervinou, Sandrine Hirschi, Frédéric Rivière, Arnaud Bourdin, François Lebargy, Stéphane Dominique, Aude Gibelin, Alexandre Chabrol, Tristan Dégot, Jacques Cadranel, Martine Reynaud-Gaubert, Marie-Pierre Debray, Sylvie Leroy, Frédéric Gagnadoux, Emmanuel Bergot, François-Xavier Blanc, Alexandra Rousseau, Raphael Borie, Pierre Yves Brillet, Guillaume Beltramo, Mallorie Kerjouan, Hilario Nunes, Olivia Freynet, Julie Traclet, Bruno Crestani, Anne-Sophie Gamez, Grégoire Prévot, Jean Pastré, Dominique Israel-Biet, Marie-Christine Dombret, Laurent Plantier, Cécile Chenivesse, Laurence Berard, Ana Nieves, Emmanuel Gomez, Dominique Valeyre, Stéphane Jouneau, Anne Gondouin, Elodie Blanchard, C. Launois, Nathalie Bautin, Jean-Marc Naccache, Vincent Cottin, Antoine Parrot, Philippe Bonniaud, Centre de référence maladies rares des maladies pulmonaires rares de l’adulte (CHU Dijon) (CRMR des maladies pulmonaires rares de l’adulte), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Sorbonne Université (SU), Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Foch [Suresnes], CHU Pontchaillou [Rennes], École des Hautes Études en Santé Publique [EHESP] (EHESP), 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 ), Hôpital Avicenne [AP-HP], Laboratoire d'Excellence INFLAMEX [Paris], Université Sorbonne Paris Cité (USPC), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Saint-Antoine [AP-HP], 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), Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, CHU Dijon, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), 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 Hospitalier Universitaire de Toulouse (CHU Toulouse), Les Hôpitaux Universitaires de Strasbourg (HUS), Nouvel Hôpital Civil de Strasbourg, Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Lille, Hôpital Albert Calmette, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Référence des Maladies Pulmonaires Rares [Hôpital Louis Pradel - HCL], Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL), Université de Lyon, CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital d'instruction des Armées Percy, Service de Santé des Armées, Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital JeanMinjoz, CHU Bordeaux [Bordeaux], Hôpital Haut-Lévêque [CHU Bordeaux], 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), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Rouen, Normandie Université (NU), CHU Tenon [AP-HP], Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), CHU Montpellier, Université de Lille, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), 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)-Centre National de la Recherche Scientifique (CNRS), Roche, Ministere de la Sante et des Solidarites, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHU Marseille-Assistance Publique-Hôpitaux de Marseille (AP-HM), Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], 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)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 ), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, education.field_of_study, Exacerbation, Cyclophosphamide, business.industry, [SDV]Life Sciences [q-bio], Population, medicine.disease, Placebo, 3. Good health, 03 medical and health sciences, Idiopathic pulmonary fibrosis, 0302 clinical medicine, 030228 respiratory system, Methylprednisolone, Internal medicine, Clinical endpoint, Medicine, 030212 general & internal medicine, business, education, Adverse effect, ComputingMilieux_MISCELLANEOUS, medicine.drug
Abstract: Summary Background The use of cyclophosphamide in patients with acute exacerbation of idiopathic pulmonary fibrosis (IPF) is unknown. Our study was designed to evaluate the efficacy and safety of four cyclophosphamide pulses in addition to high-dose methylprednisolone in this population. Methods In this double-blind, placebo-controlled trial done in 35 departments across 31 hospitals in France, adult patients (≥18 years) with acute exacerbation of IPF and those with suspected acute exacerbation of IPF were randomly assigned in a 1:1 ratio using a web-based system to receive either intravenous pulses of cyclophosphamide (600 mg/m2) plus uromitexan as haemorrhagic cystitis prophylaxis (200 mg/m2) at the time of cyclophosphamide administration and then again, 4 h later, or placebo at days 0, 15, 30, and 60. Random assignment was stratified according to the severity of IPF and was block-balanced with variable block sizes of four or six patients. Patients receiving mechanical ventilation, with active infection, with active cancer, or who were registered on the lung transplant waiting list were excluded. All patients received standardised high-dose glucocorticoids. The investigators, patients, and the sponsor were masked to the treatment assignments. The primary endpoint was 3-month all-cause mortality, analysed by a χ2 test adhering to an intention-to-treat principle. The trial is now complete and registered with ClinicalTrials.gov , NCT02460588 . Findings Between Jan 22, 2016, and July 19, 2018, 183 patients were assessed for eligibility, of whom 120 patients were randomly assigned and 119 patients (62 [52%] with severe IPF) received at least one dose of cyclophosphamide (n=60) or placebo (n=59), all of whom were included in the intention-to-treat analysis. The 3-month all-cause mortality was 45% (27/60) in patients given cyclophosphamide compared with 31% (18/59) in the placebo group (difference 14·5% [95% CI −3·1 to 31·6]; p=0·10). Similar results were found after adjustment by IPF severity (odds ratio [OR] 1·89 [95% CI 0·89–4·04]). The risk of death at 3 months, independent of the treatment received, was higher with severe than non-severe IPF (OR 2·62 [1·12–6·12]) and was lower with the use of antifibrotic therapy (OR 0·33 [0·13–0·82]). Adverse events were similar between groups by 6 months (25 [42%] in the cyclophosphamide group vs 30 [51%] in the placebo group) and their proportion, including infections, did not differ. Overall infection was the main adverse event and occurred in 20 (33%) of 60 patients in the cyclophosphamide group versus 21 (36%) of 59 patients in the placebo group. Interpretation In patients with acute exacerbation of IPF, adding intravenous cyclophosphamide pulses to glucocorticoids increased 3-month mortality. These findings provide evidence against the use of intravenous cyclophosphamide in such patients. Funding Programme Hospitalier de Recherche Clinique of the French Ministry of Health (PHRC 2014–502), Roche Pharmaceuticals.
Published: 2022

2. Thyroiditis and immune check point inhibitors: the post-marketing experience using the French National Pharmacovigilance database

Author: Nadine Petitpain, Julie Garon-Czmil, Franck Rouby, Marion Sassier, Georges Weryha, Marc Klein, Pierre Gillet, Samy Babai, Melissa Yelehe-Okouma, Centre Régional de PharmacoVigilance de Lorraine (CRPV Lorraine), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Endocrinologie et Gynécologie Médicale [CHRU Nancy], 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), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Pharmacologie [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 régional de pharmacovigilance [CHU Henri-Mondor], CHU Henri Mondor [Créteil], Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), CHU Marseille-Assistance Publique-Hôpitaux de Marseille (AP-HM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), and CHU Henri Mondor
Subjects: Adult, Male, Thyroiditis, Time Factors, Databases, Factual, Levothyroxine, Ipilimumab, Pembrolizumab, Antibodies, Monoclonal, Humanized, computer.software_genre, Risk Assessment, 030226 pharmacology & pharmacy, Pharmacovigilance, Young Adult, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Risk Factors, Product Surveillance, Postmarketing, Adverse Drug Reaction Reporting Systems, Humans, Medicine, Pharmacology (medical), ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Aged, 80 and over, Pharmacology, Database, business.industry, Thyroid, Middle Aged, medicine.disease, 3. Good health, Discontinuation, Nivolumab, medicine.anatomical_structure, Female, France, business, computer, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, medicine.drug
Abstract: Immunotherapy with immune checkpoint inhibitors (ICIs) for cancer has become increasingly prescribed in recent years. Indeed, it is used to treat both solid and hematological malignancies due to their considerable potential in treating melanoma, non-small cell lung and other cancers. Immune-mediated related adverse endocrine toxicity, and especially thyroiditis, is seen as a growing problem needing specific screening and management. This study aims at describing thyroid dysfunctions induced by the ICIs marketed in France, which are registered in the French Pharmacovigilance database. This database was queried for nivolumab, pembrolizumab, and ipilimumab-induced adverse drug reactions reported before April 30, 2017. Both a pharmacologist and an endocrinologist have reviewed each case to select only those of peripheral thyroiditis (thyrotoxicosis and hypothyroidism). During this period, 110 thyroiditis following ICI therapy were reported. Sex/ratio was around one. Most of the cases (47.2%) were asymptomatic. Although some thyrotoxicosis cases were severe, no orbitopathy was reported. Hypothyroidism and thyrotoxicosis were equally described. Antithyroid antibodies were positive in only 16% patients. The ultrasonography was informative in 19% patients. Levothyroxine supplementation was necessary in 57% patients, leading to 19% recovery. With a dedicated optimized management, most of the cases did not require immunotherapy discontinuation. Finally, immune-mediated related thyroiditis is increasing due to a wider prescription of ICI therapy in various cancer conditions and systematic screening. Often asymptomatic, they lead to a local activation accompanied by hormonal deficiency in the long run. It is necessary to carry out an early and sustained multidisciplinary screening to allow immunotherapy continuation.
Published: 2018

3. In vivo characterization of healthy human skin with a novel, non‐invasive imaging technique: line‐field confocal optical coherence tomography

Author: J.-L. Perrot, J. Perez, Joseph Malvehy, V. Del Marmol, O. Yélamos, M. Miyamoto, J. Monnier, Pietro Rubegni, Linda Tognetti, Elisa Cinotti, C. Orte Cano, S. Puig, Arnaud Dubois, Mariano Suppa, M. Fontaine, Département de dermatologie, CHU Marseille, CHU Marseille, Laboratoire Charles Fabry / Biophotonique, Laboratoire Charles Fabry (LCF), Institut d'Optique Graduate School (IOGS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut d'Optique Graduate School (IOGS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), and Department of Dermatology, University Hospital of Saint-Etienne
Subjects: Adult, Keratinocytes, Male, Confocal, Human skin, Dermatology, 01 natural sciences, 010309 optics, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Optical coherence tomography, 0103 physical sciences, medicine, Stratum corneum, Humans, ComputingMilieux_MISCELLANEOUS, Skin, [PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics], integumentary system, medicine.diagnostic_test, business.industry, Histological Techniques, Cheek, Infectious Diseases, medicine.anatomical_structure, Dermal papillae, Female, Epidermis, Tomography, business, Tomography, Optical Coherence, Biomedical engineering
Abstract: Background Line-field confocal optical coherence tomography (LC-OCT) is a non-invasive optical technique recently developed for skin examination in vivo. It provides real-time, high-resolution vertical images with an isotropic resolution of similar to 1 mu m and a penetration depth of similar to 500 mu m. Objectives Study goals were to qualitatively/quantitatively characterize healthy skin at different body sites using LC-OCT. Methods The skin of young healthy volunteers was imaged with a handheld LC-OCT imaging device. Seven body sites (back of the hand, forehead, cheek, nose, chest, forearm and back) were investigated. An independent qualitative [cutaneous structures' description; visibility of keratinocytes' nuclei and dermal-epidermal junction (DEJ)] and quantitative [stratum corneum (SC)/epidermal thicknesses; height of dermal papillae] assessment of the LC-OCT images was performed. Results A total of 88 LC-OCT images were collected from 29 participants (20 females; nine males; mean age 25.9 years). Keratinocytes' nuclei and DEJ were visible in the totality of images. The different layers of the epidermis and the remaining cutaneous structures/findings were visualized. Body sites-related variability was detected for SC/epidermal thicknesses and height of dermal papillae. Inter-observer agreement was excellent (SC thickness), good-to-excellent (epidermal thickness) and moderate-to-good (papillae). Conclusions Line-field confocal-OCT provides non-invasive, real-time imaging of the skin in vivo with deep penetration and high resolution, enabling the visualization of single cells. The histology-like vertical view provides an easy way to recognize/measure different cutaneous structures/findings. LC-OCT appears as a promising technique for the examination of physiological/pathological skin.
Published: 2020

4. Pitch perception modification due to antiepileptics: A literature and pharmacovigilance databases review

Author: Marie-Noëlle Osmont, Sylvie Picard, Hoel Charbonnel, Eric Bellissant, Lucie-Marie Scailteux, Elisabeth Polard, Adeline Degremont, Louise Triquet, Anne Default, Guillaume Gentilhomme, Brendan Le Daré, CHU Pontchaillou [Rennes], Hôpital Lapeyronie [Montpellier] (CHU), Chercheur indépendant, Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Marseille-Assistance Publique-Hôpitaux de Marseille (AP-HM), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Pediatrics, medicine.medical_specialty, Lacosamide, [SDV]Life Sciences [q-bio], Lamotrigine, 030226 pharmacology & pharmacy, Felbamate, 03 medical and health sciences, 0302 clinical medicine, Antiepileptic, Pharmacovigilance, medicine, Pharmacology (medical), Perfect pitch, Oxcarbazepine, business.industry, Carbamazepine, Hearing loss, Pitch perception, 3. Good health, Levetiracetam, business, Primidone, psychological phenomena and processes, medicine.drug
Abstract: National audience; Pitch perception modifications are among the little-known adverse effects observed with antiepileptics, mainly affecting patients treated with carbamazepine (CBZ). Here, we describe an original French case of pitch perception modification due to CBZ resulting in perfect pitch loss. We also reviewed the literature as well as French and world health organisation global pharmacovigilance database. The case report concerns a 22-year-old patient with perfect pitch with untreated left temporal partial epilepsy. Following a generalized seizure, the introduction of CBZ prolonged release (200mg twice a day) is decided. As soon as CBZ is introduced, the patient notices a change in pitch perception, about a semitone lower. This adverse effect persisted despite a gradual decrease in doses. The patient reported a total recovery of his perfect pitch when CBZ stopped completely 11 years later. In the French pharmacovigilance database, only one other case of pitch perception modification under CBZ was recorded (no cases were found with oxcarbazepine, lacosamide, sodium valproate, lamotrigine, levetiracetam, phenobarbital, phenytoin, primidone, ethosuximide, vigabatrine, felbamate, gabapentin, tiagabine and topiramate). In the literature, 27 cases of pitch perception modification have been published with CBZ, 1 case with oxcarbazepine and 1 case with lacosamide. Pitch perception modification is a very rare adverse effect of CBZ, oxcarbazepine and lacosamide, identified in the literature mainly in the Japanese population, in experienced musicians. A rapid onset after the introduction of treatment, a complete resolution of symptoms, in most cases upon discontinuation of treatment, is observed, with no sequelae reported. Due to the impact on quality of life, especially in patients whose profession is related to music, knowledge of this adverse event seems important to evoke this diagnosis.
Published: 2020

5. Factors Associated With Short-term Relapse in Patients With Pemphigus Who Receive Rituximab as First-line Therapy

Author: Mignard, Claire, Maho-Vaillant, Maud, Golinski, Marie-Laure, Balayé, Pierre, Prost-Squarcioni, Catherine, Houivet, Estelle, Calbo, Sé Bastien, Labeille, Bruno, Picard-Dahan, Catherine, Konstantinou, Maria Polina, Chaby, Guillaume, Richard, Marie-Aleth, Bouaziz, Jean-David, Duvert-Lehembre, Sophie, Delaporte, Emmanuel, Bernard, Philippe, Caux, Frédéric, Alexandre, Marina, Ingen-Housz-Oro, Saskia, Vabres, Pierre, Quéreux, Gaelle, Dupuy, Alain, Debarbieux, Sebastien, Avenel-Audran, Martine, d'Incan, Michel, Bedane, Christophe, Beneton, Nathalie, Jullien, Denis, Dupin, Nicolas, Misery, Laurent, Machet, Laurent, Beylot-Barry, Marie, Dereure, Olivier, Sassolas, Bruno, Bénichou, Jacques, Joly, Pascal, Hebert, Vivien, Calbo, Sébastien, Service de dermatologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Dermatologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Service de dermatologie [Paris], Université Paris Diderot - Paris 7 (UPD7)-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), Unité de biostatistiques [CHU Rouen], University Hospital of St-Etienne, Department of Dermatology, Service de Dermatologie, Hôpital Bichat, AP-HP, Service de dermatologie [CHU d'Amiens-Picardie], CHU Amiens-Picardie, Département de dermatologie, CHU Marseille, CHU Marseille, Service de Dermatologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Claude Huriez [Lille], CHU Lille, Immunodermatologie, Cytokines, Cancer - EA 7319 (ICA), Université de Reims Champagne-Ardenne (URCA), Service de dermatologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Henri Mondor, Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Clinical and Translational Research in Skin Cancer (CRCINA-ÉQUIPE 2), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), 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)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-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)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service de Dermatologie [Rennes] = Dermatology [Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de Dermatologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Clermont-Ferrand, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service de Dermatologie [CHU Limoges], CHU Limoges, Centre Hospitalier Le Mans (CH Le Mans), Club Rhumatismes et Inflammation, EA1833, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de dermatologie, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Bordeaux [Bordeaux], Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Hôpital Charles Nicolle [Rouen], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de Dermatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), CHU Henri Mondor [Créteil], Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: integumentary system, immune system diseases, [SDV]Life Sciences [q-bio], education, [SDV.CAN]Life Sciences [q-bio]/Cancer, macromolecular substances
Abstract: International audience; Importance: Rituximab and short-term corticosteroid therapy are the criterion standard treatments for patients with newly diagnosed moderate to severe pemphigus.Objective: To examine factors associated with short-term relapse in patients with pemphigus treated with rituximab.Design, setting, and participants: This post hoc analysis of a randomized clinical trial (Comparison Between Rituximab Treatment and Oral Corticosteroid Treatment in Patients With Pemphigus [RITUX 3]) conducted from January 1, 2010, to December 31, 2015, included patients from 20 dermatology departments of tertiary care centers in France from the RITUX 3 trial and 3 newly diagnosed patients treated according to the trial protocol. Data analysis was performed from February 1 to June 30, 2019.Exposure: Patients randomly assigned to the rituximab group in the RITUX 3 trial and the 3 additional patients were treated with 1000 mg of intravenous rituximab on days 0 and 14 and 500 mg at months 12 and 18 combined with a short-term prednisone regimen.Main outcomes and measures: Baseline (pretreatment) clinical and biological characteristics (Pemphigus Disease Area Index [PDAI] score, ranging from 0-250 points, with higher values indicating more severe disease) and changes in anti-desmoglein (DSG) 1 and anti-DSG3 values as measured by enzyme-linked immunosorbent assay during the 3 months after rituximab treatment were compared between patients with disease relapse and those who maintained clinical remission during the first 12 months after treatment. The positive and negative predictive values of these factors were calculated.Results: Among 47 patients (mean [SD] age, 54.3 [17.0] years; 17 [36%] male and 30 [64%] female) included in the study, the mean (SD) baseline PDAI score for patients with relapsing disease was higher than that of the patients with nonrelapsing disease (54 [33] vs 28 [24]; P = .03). At month 3, 7 of 11 patients with relapsing disease (64%) vs 7 of 36 patients with nonrelapsing disease (19%) had persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher (P = .01). A PDAI score of 45 or higher defining severe pemphigus and/or persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher at month 3 provided a positive predictive value of 50% (95% CI, 27%-73%) and a negative predictive value of 94% (95% CI, 73%-100%) for the occurrence of relapse after rituximab.Conclusions and relevance: The findings suggest that initial PDAI score and changes in anti-DSG antibody values after the initial cycle of rituximab might help differentiate a subgroup of patients with high risk of relapse who might benefit from maintenance rituximab infusion at month 6 from a subgroup of patients with low risk of relapse who do not need early maintenance therapy.Trial registration: NCT00784589.
Published: 2020

6. Acute Coronary Syndrome With Immune Checkpoint Inhibitors: A Proof-of-Concept Case and Pharmacovigilance Analysis of a Life-Threatening Adverse Event

Author: Charles Dolladille, Franck Thuny, Franck Paganelli, Ugo Scemama, Ariel Cohen, Franck Rouby, Joachim Alexandre, Stéphane Ederhy, Joe-Elie Salem, Jennifer Cautela, 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 Nord [CHU - APHM], Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), CHU Marseille-Assistance Publique-Hôpitaux de Marseille (AP-HM), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [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), CIC Paris Est, 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], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Département de Pharmacologie [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), Signalisation, électrophysiologie et imagerie des lésions d’ischémie-reperfusion myocardique (SEILIRM), Normandie Université (NU)-Normandie Université (NU), Thrombose, atherothrombose et pharmacologie appliquée, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Pharmacologie médicale [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), Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and CCSD, Accord Elsevier
Subjects: Male, medicine.medical_specialty, Acute coronary syndrome, Immune checkpoint inhibitors, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Proof of Concept Study, Pharmacovigilance, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, medicine, Humans, Immunologic Factors, 030212 general & internal medicine, Acute Coronary Syndrome, Intensive care medicine, Adverse effect, Aged, Aged, 80 and over, business.industry, Middle Aged, medicine.disease, Causality, Thrombosis, 3. Good health, [SDV] Life Sciences [q-bio], Female, Cardiology and Cardiovascular Medicine, business, Isolated cases
Abstract: International audience; Isolated cases of acute coronary syndrome (ACS) associated with immune checkpoint inhibitors (ICIs) have been described without the establishment of a formal cause-and-effect relationship between treatment and adverse event. We reported a case of ACS after the first administration of an ICI and with a fatal recurrence in another coronary area immediately after readministration. According to guidelines, causality was considered to be certain. Subsequently, we queried the French pharmacovigilance database and found 4 cases of ACS with coronary artery thrombosis. Causality was probable in those patients. These data suggest that ACS may be another life-threatening cardiac adverse event occurring with ICI exposure.
Published: 2020

7. Medication Reconciliation Associated with Comprehensive Geriatric Assessment in Older Patients with Cancer: ChimioAge Study

Author: Couderc, Anne-Laure, Boisseranc, Celia, Rey, Dominique, Nouguerede, Emilie, Greillier, Laurent, Barlesi, Fabrice, Duffaud, Florence, Deville, Laurent, Honoré, Stéphane, Villani, Patrick, Correard, Florian, Assistance Publique - Hôpitaux de Marseille (APHM), Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Service d’Oncologie Médicale [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, and CHU Marseille-Assistance Publique-Hôpitaux de Marseille (AP-HM)
Subjects: Aged, 80 and over, Male, geriatric assessment, [SDV]Life Sciences [q-bio], [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Clinical Decision-Making, antineoplastic protocols, [SDV.CAN]Life Sciences [q-bio]/Cancer, Medical Oncology, Patient Care Planning, [SHS]Humanities and Social Sciences, [SDV.ETH]Life Sciences [q-bio]/Ethics, aged, Neoplasms, Clinical Interventions in Aging, Polypharmacy, medication reconciliation, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Humans, Female, Prospective Studies, ComputingMilieux_MISCELLANEOUS, Original Research, treatment failure
Abstract: Anne-Laure Couderc,1,2 Celia Boisseranc,3 Dominique Rey,1 Emilie Nouguerede,1 Laurent Greillier,4,5 Fabrice Barlesi,4,5 Florence Duffaud,4,6 Jean-Laurent Deville,6 Stéphane Honoré,3,4 Patrick Villani,1,2 Florian Correard3,4 1Internal Medicine, Geriatry and Therapeutic Unit, AP-HM, Marseille, France;Coordination Unit for Geriatric Oncology (UCOG), PACA West, Marseille, France; 2Aix-Marseille Université, CNRS, EFS, ADES, Marseille, France; 3Pharmacology Department, AP-HM, Marseille, France; 4Aix-Marseille University, Marseille, France; 5Multidisciplinary Oncology and Therapeutic Innovations Unit, AP-HM, Marseille, France; 6Oncology Unit, AP-HM, Marseille, FranceCorrespondence: Anne-Laure CoudercCoordination Unit for Geriatric Oncology (UCOG), PACA West, University Hospital of Marseille (AP-HM), 270 Boulevard De Sainte Marguerite, Marseille 13009, FranceTel +33 491744530Fax +33 491744833Email anne-laure.couderc@ap-hm.frBackground: Polymorbidity induces polypharmacy in older patients may lead to potential drug–drug interactions (DDI) which can modify the tolerance and safety of oncological treatments and alter the intended therapeutic effect. The objective of our study was to describe the decision-making process for oncological treatment and related outcomes, in a population of older adults undergoing a comprehensive geriatric assessment (CGA) associated to a comprehensive medication reconciliation (CMR) prior to initiating oncological treatment.Methods: ChimioAge is a prospective observational study conducted between 01/2017 and 07/2018 at Marseille University Hospital and approved by the French National Ethics Committee. It comprised all consecutive patients aged 70 years and over who were referred for a CGA as part of CMR, before initiating systemic treatment.Results: One hundred and seventy-one cancer patients were included. Mean age was 79.2 years, over half had metastatic cancers, 75% had an ECOG performance status zero or one, and two-thirds were independent in daily activities. Two-thirds of the patients had polypharmacy and the CMR identified potential DDI with systemic treatment in 43.3% of patients. Following the CGA, the CMR and the hospital oncologists decision, 30% of the patients received adapted systemic treatment with reduced doses at initiation. They presented fewer toxicities – irrespective of grade and type – than patients who received standard treatment (p< 0.001) and had comparable overall survival (Log rank p=0.21).Conclusion: This is one of the first studies to highlight the value in conducting CMR and a CGA simultaneously before initiating systemic treatment in older patients with cancer. These two evaluations could give oncologists decisive information to personalize cancer treatment of older patients and optimize treatment dose to offer the best efficacy and minimize toxicity.Keywords: aged, antineoplastic protocols, geriatric assessment, medication reconciliation, treatment failure
Published: 2020

8. Antibiotic resistance: Tools for effective translational research

Author: Solen Kernéis, C. Dumartin, Romain Guilhaumou, Marie-Clémence Verdier, Didier Concordet, Joanie del Bano, Mohamed Khelifa, Claire Le Jeunne, Bruno Valtier, Evelyne Jouvin-Marche, Antoine Andremont, William Couet, Marie-Cécile Ploy, Mourez Michaël, Cyril Guyard, Bruno Coignard, Didier Guillemot, Alain Bousquet-Mélou, Christian Brun-Buisson, Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, Pfizer, CHU Cochin [AP-HP], 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], Epidémiologie et modélisation de la résistance aux antimicrobiens - Epidemiology and modelling of bacterial escape to antimicrobials, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Innovations Thérapeutiques et Résistances (InTheRes), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Santé publique France, Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix-Marseille Université - Faculté de pharmacie (AMU PHARM), Aix Marseille Université (AMU), BIOASTER, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Sanofi-Aventis R&D, SANOFI Recherche, Evotec, 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], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biostatistique, Biomathématique, Pharmacoépidémiologie et Maladies Infectieuses (B2PHI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Raymond Poincaré [AP-HP], Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Direction des maladies infectieuses - Infectious Diseases Division [Saint-Maurice], Santé publique France - French National Public Health Agency [Saint-Maurice, France], Service de Pharmacologie Clinique [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), 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), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), BIOASTER Microbiology Technology Institute [Lyon], Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Marseille-Assistance Publique-Hôpitaux de Marseille (AP-HM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), and Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges
Subjects: medicine.medical_specialty, media_common.quotation_subject, Public health, Microbiota, [SDV]Life Sciences [q-bio], Translational research, 030226 pharmacology & pharmacy, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Effective interventions, Antibiotic resistance, Impact, Risk analysis (engineering), Work (electrical), medicine, Stewardship, Pharmacology (medical), Quality (business), Profitability index, Antibio-resistance, Business, Innovation, media_common
Abstract: Refers to : Marie-Cécile Ploy, Antoine Andremont, Bruno Valtier, Claire Le Jeunne - Antibiorésistance : outils pour une recherche translationnelle efficace - Therapies, Volume 75, Issue 1, January–February 2020, Pages 1-6; National audience; The rising emergence of bacterial resistances has led to a crisis which threatens human, animal and environmental health. The impact of the emergency is enormous in terms of public health and economics. Although there is a global awareness of the warnings and programmes supporting innovative actions to combat fight against antibiotic resistance, it must be admitted that proposed new antibiotics fail to find the economic profitability necessary for them to reach the market and become available for patients and the community. Moreover, it is necessary to develop tools/indicators to define effective interventions against antibiotic resistance. The work of the think-tank reported in this article concentrated on two aspects of translational research: - prevention and the impact on health of the antibiotic resistance issue, and - the specific requirements of clinical research leading to innovation in the fight against antibiotic resistance. This article, which reflects the thoughts of a group of French experts, proposes directly operational solutions which could be rapidly implemented and radically transform the quality and quantity of our resources available for the combat.
Published: 2020

9. Dimension reduction and analysis of a 10-year physicochemical and biological water database applied to water resources intended for human consumption in the Provence-Alpes-Cote d'Azur region, France

Author: Vincent Valles, Tarik Bahaj, Ilias Kacimi, Moad Morarech, Laurent Barbiero, Abdessamad Tiouiouine, Tarik Bouramtane, Marc Moulin, Fabrice Dassonville, Suzanne Yameogo, Université Mohammed V de Rabat [Agdal], Institut de l'Environnement et Recherches Agricoles [Ouagadougou] (INERA), Institut de Recherche pour le Développement (IRD), Environnement Méditerranéen et Modélisation des Agro-Hydrosystèmes (EMMAH), Avignon Université (AU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Géosciences Environnement Toulouse (GET), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD), Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), CHU Marseille-Assistance Publique-Hôpitaux de Marseille (AP-HM), Bureau de Recherches Géologiques et Minières (BRGM) (BRGM), Université Abdelmalek Essaâdi (UAE), Université Mohammed V de Rabat [Agdal] (UM5), Centre national de la recherche scientifique et technologique [Ouagadougou] (CNRST), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), and Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille
Subjects: Multivariate statistics, lcsh:Hydraulic engineering, multivariate statistics, 0208 environmental biotechnology, Geography, Planning and Development, Context (language use), 02 engineering and technology, 010501 environmental sciences, Aquatic Science, computer.software_genre, 01 natural sciences, Biochemistry, hydrochemistry, hydrochemistry, water resource, hydrogeology, multivariate statistics, France, lcsh:Water supply for domestic and industrial purposes, lcsh:TC1-978, Dimension (data warehouse), 0105 earth and related environmental sciences, Water Science and Technology, lcsh:TD201-500, Database, Dimensionality reduction, 15. Life on land, [SDE.ES]Environmental Sciences/Environmental and Society, 6. Clean water, 020801 environmental engineering, Water resources, Ranking, hydrogeology, 13. Climate action, Principal component analysis, [SDE]Environmental Sciences, water resource, Environmental science, Water quality, France, computer
Abstract: The SISE-Eaux database of water intended for human consumption, archived by the French Regional Health Agency (ARS) since 1990, is a rich source of information. However, more or less regular monitoring over almost 30 years and the multiplication of parameters lead to a sparse matrix (observations &times, parameters) and a large dimension of the hyperspace of data. These characteristics make it difficult to exploit this database for a synthetic mapping of water quality, and to identify of the processes responsible for its diversity in a complex geological context and anthropized environment. A 10-year period (2006&ndash, 2016) was selected from the Provence-Alpes- C&ocirc, te d&rsquo, Azur region database (PACA, southeastern France). We extracted 5,295 water samples, each with 15 parameters. A treatment by principal component analysis (PCA) followed with orthomax rotation allows for identifying and ranking six principal components (PCs) totaling 75% of the initial information. The association of the parameters with the principal components, and the regional distribution of the PCs make it possible to identify water-rock interactions, bacteriological contamination, redox processes and arsenic occurrence as the main sources of variability. However, the results also highlight a decrease of useful information, a constraint linked to the vast size and diversity of the study area. The development of a relevant tool for the protecting and managing of water resources will require identifying of subsets based on functional landscape units or the grouping of groundwater bodies.
Published: 2020

10. Impaired cortico-limbic functional connectivity in schizophrenia patients during emotion processing

Author: Pierre-Emmanuel Lazerges, Olivier Blin, Claire Boutet, Jean-Michel Azorin, Eric Fakra, Nematollah Jaafari, Magali Comte, Thierry Sage, Aïda Cancel, Fabien C Schneider, El Chérif Ibrahim, Jennifer T. Coull, Xavier Zendjidjian, Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Pôle de Psychiatrie, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), CLINEA - Clinique de santé mentale, L'escale [Saint-Victoret, France], ORPEA Groupe, Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Laboratoire de neurosciences expérimentales et cliniques (LNEC), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pôle de psychiatrie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-CHU Marseille, COMBE, Isabelle, Institut de Neurosciences de la Timone ( INT ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Neurosciences Cognitives [Marseille] ( LNC ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Universitaire de Saint-Etienne ( CHU de Saint-Etienne ), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière ( NEMESIS-CRICM ), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière ( CRICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de psychopathologie et psychologie médicale ( LPPM ), Université de Bourgogne ( UB ), Immunologie antivirale systémique et cérébrale, Université Paris-Sud - Paris 11 ( UP11 ) -IFR93-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Neurobiologie des interactions cellulaires et neurophysiopathologie - NICN ( NICN ), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique ( CNRS ), Assistance Publique - Hôpitaux de Marseille ( APHM ) -Hôpital Sainte-Marguerite [CHU - APHM] ( Hôpitaux Sud ) -CHU Marseille, Microbes évolution phylogénie et infections ( MEPHI ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Clinical Investigation Centre (CIC-UPCET) and Department of Clinical Pharmacology, Centre investigation clinique - Unité de pharmacologie clinique et d'évaluations thérapeutiques ( CIC-UPCET ), Assistance Publique - Hôpitaux de Marseille ( APHM ) -Assistance Publique - Hôpitaux de Marseille ( APHM ), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE)
Subjects: Cognitive Neuroscience, Experimental and Cognitive Psychology, Affect (psychology), Amygdala, behavioral disciplines and activities, 03 medical and health sciences, 0302 clinical medicine, mental disorders, medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Prefrontal cortex, Anterior cingulate cortex, prefrontal cortex, medicine.diagnostic_test, Cognition, General Medicine, Original Articles, amygdala, medicine.disease, functional magnetic resonance imaging, 030227 psychiatry, Dorsolateral prefrontal cortex, schizophrenia, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, anterior cingulate cortex, medicine.anatomical_structure, nervous system, Schizophrenia, affect, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Functional magnetic resonance imaging, Psychology, Neuroscience, 030217 neurology & neurosurgery, psychological phenomena and processes
Abstract: International audience; Functional dysconnection is increasingly recognized as a core pathological feature in schizophrenia. Aberrant interactions between regions of the cortico-limbic circuitmay underpin the abnormal emotional processing associated with this illness. We used a functionalmagnetic resonance imaging paradigmdesigned to dissociate the various components of the corticolimbic circuit (i.e. a ventral automatic circuit that is intertwined with a dorsal cognitive circuit), to explore bottom-up appraisal as well as top-down control during emotion processing. In schizophrenia patients compared with healthy controls, bottom-up processes were associated with reduced interaction between the amygdala and both the anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex. Contrariwise, top-down control processes led to stronger connectivity between the ventral affective and the dorsal cognitive circuits, i.e. heightened interactions between the ventral ACC and the dorsolateral prefrontal cortex as well as between dorsal and ventral ACC. These findings offer a comprehensive view of the cortico-limbic dysfunction in schizophrenia. They confirmprevious results of impaired propagation of information between the amygdala and the prefrontal cortex and suggest a defective functional segregation in the dorsal cognitive part of the cortico-limbic circuit.
Published: 2017

11. Difference in imaging biomarkers of neurodegeneration between early and late-onset amnestic Alzheimer's disease

Author: Anne-Laure Aziz, Jean-Philippe Ranjeva, Eric Guedj, José Boucraut, Lejla Koric, Lauréline Duprat, Olivier Felician, Sven Joubert, Bernard Giusiano, Mathieu Ceccaldi, Mira Didic, Claude Gueriot, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche de l'Institut universitaire de gériatrie, Université de Montréal (UdeM), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC), Service de neurologie et de neuropsychologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire d'Immunologie [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Centre National de la Recherche Scientifique (CNRS), Fondation FondaMental [Créteil], Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Centre de Mémoire de Ressources et de Recherche [Hôpital La Timone, Marseille], Hôpital de la Timone [CHU - APHM] (TIMONE)-CHU Marseille, Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), Neurobiologie intégrative et adaptative (NIA), Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS), Service Central de Biophysique et de Médecine Nucléaire, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Mémoire de Ressources et de Recherche, CHU Marseille, and Guedj, Eric
Subjects: Male, 0301 basic medicine, Aging, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Disease, Neuroimaging biomarkers, Severity of Illness Index, Cognition, 0302 clinical medicine, Semantic memory, Early-onset Alzheimer's disease, Age of Onset, Aged, 80 and over, General Neuroscience, Neurodegeneration, Brain, Middle Aged, Alzheimer's disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Cardiology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Psychology, Amyloid, medicine.medical_specialty, Temporoparietal junction, Neuroimaging, 03 medical and health sciences, Atrophy, Alzheimer Disease, Memory, Internal medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], snc, Positron emission tomography imaging, Aged, medicine.disease, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Glucose, 030104 developmental biology, Positron-Emission Tomography, Posterior cingulate, Nerve Degeneration, Neurology (clinical), Geriatrics and Gerontology, Age of onset, Neuroscience, Biomarkers, 030217 neurology & neurosurgery, Developmental Biology
Abstract: International audience; Neuroimaging biomarkers differ between patients with early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD). Whether these changes reflect cognitive heterogeneity or differences in disease severity is still unknown. This study aimed at investigating changes in neuroimaging biomarkers, according to the age of onset of the disease, in mild amnestic Alzheimer's disease patients with positive amyloid biomarkers in cerebrospinal fluid. Both patient groups were impaired on tasks assessing verbal and visual recognition memory. EOAD patients showed greater executive and linguistic deficits, while LOAD patients showed greater semantic memory impairment. In EOAD and LOAD, hypometabolism involved the bilateral temporoparietal junction and the posterior cingulate cortex. In EOAD, atrophy was widespread, including frontotemporoparietal areas, whereas it was limited to temporal regions in LOAD. Atrophic volumes were greater in EOAD than in LOAD. Hypometabolic volumes were similar in the 2 groups. Greater extent of atrophy in EOAD, despite similar extent of hypometabolism, could reflect different underlying pathophysiological processes, different glucose-based compensatory mechanisms or distinct level of premorbid atrophic lesions.
Published: 2017

12. How to improve vaccine acceptability (evaluation, pharmacovigilance, communication, public health, mandatory vaccination, fears and beliefs)

Author: Geneviève Chêne, Franck Gérald, Thomas Borel, Géraldine Ménin, Farid Kheloufi, Jacques Morel, Marie-Christine Truchet, Claire Roger, Franck Rouby, Véronique Lamarque-Garnier, Jehan-Michel Behier, Odile Launay, Clémentine Schilte, Mathieu Molimard, Alain Dutilleul, Véronique Dufour, Laurent Simon, Arnaud Gagneur, Stéphane Schück, Annick Opinel, Jean-Louis Koeck, François Faurisson, Benoît Soubeyrand, Brigitte Autran, Soizic Courcier, Telma Lery, Odile Gelpi, Xavier Bresse, Sanofi Pasteur [Lyon, France], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Pasteur [Paris] (IP), CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Takeda France, Les entreprises du Médicament (LEEM), Sanofi Pasteur MSD, Epidémiologie, santé publique et développement, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR99-ISPED, Laboratoire GlaxoSmithKline [ Marly-le-Roi], Infovac-France, Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Sherbrooke (UdeS), ACS-France - Action Contre les Spondylarthropathies (Action Contre les Spondylarthropathies ), Assistance Publique - Hôpitaux de Marseille (APHM), Direction centrale du service de santé des armées (DCSSA), EVAL Santé, Janssen Cilag, CHU Bordeaux [Bordeaux], Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Kappa, Blossom Vaccinology, Pfizer, Institut Pasteur [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)-Groupe hospitalier Broca-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Marseille-Assistance Publique-Hôpitaux de Marseille (AP-HM), Le pharmacien de France, and CCSD, Accord Elsevier
Subjects: Vaccination Coverage, 030309 nutrition & dietetics, MESH: Pharmacovigilance, Motivational interviewing, Mandatory Programs, Pharmacovigilance, 0302 clinical medicine, Information system, Information systems, MESH: Health Education / trends, Pharmacology (medical), Health Education, Vaccines, 0303 health sciences, Schools, Communication, Vaccination, Hesitancy, MESH: Vaccination Coverage, MESH: Patient Acceptance of Health Care, Mandatory vaccination, 030205 complementary & alternative medicine, 3. Good health, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Communication, France, Public Health, MESH: Public Health, MESH: Mandatory Programs, medicine.medical_specialty, MESH: Schools, MESH: Vaccination / trends, MESH: Motivation, Education, 03 medical and health sciences, medicine, Humans, Motivation, Medical education, Immunization Programs, Public health, Patient Acceptance of Health Care, MESH: Immunization Programs / trends, MESH: France, MESH: Vaccines, Intervention (law), Immunization, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Business, Vaccine
Abstract: International audience; A flagship recommendation of the citizen's steering committee on immunization, the mandatory immunization for infants extended to 11 vaccines, introduced in January 2018, is part of a set of recommendations that must be considered as a whole, each component being indispensable to the achievement of objectives: restore confidence in vaccination and increase immunization coverage. Roundtable # 6 participants identified a decade of concrete initiatives that could address, at least in part, the committee's recommendations, including: developing information systems and data generation; simplify the vaccination journey and increase vaccination opportunities; developing training of health professionals; learning vaccines at school; using motivational interviewing in educational intervention; undertaking local initiatives; improving supply and communicate on the value of vaccines. To carry out these actions, it has been proposed that a joint ministerial task-force bringing together the different stakeholders at the national level should be set up to promote their implementation and follow-up, and at regional level, the establishment of an Agences régionales de santé awareness plan making vaccination a priority.
Published: 2019

13. EWSR1-PATZ1 gene fusion may define a new glioneuronal tumor entity

Author: Anne-Isabelle Bertozzi, Emmanuelle Uro-Coste, Claude-Alain Maurage, Sarah Péricart, Sergio Boetto, Yvan Nicaise, Sophie Le Guellec, Camille Franchet, Alix Delrieu, Matthieu Vinchon, David Grand, Frédéric Escudié, David T.W. Jones, Valérie Rigau, Anne Gomez-Brouchet, Aurore Siegfried, Jean-Christophe Sol, Audrey Rousseau, Franck-Emmanuel Roux, Dominique Figarella-Branger, Département de Pathologie [CHU Toulouse], CHU Toulouse [Toulouse], Centre de Recherches en Cancérologie de Toulouse (CRCT), 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)-Centre National de la Recherche Scientifique (CNRS), Design and Application of Innovative Local Treatments in Glioblastoma (CRCINA-ÉQUIPE 17), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), 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)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-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)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Département de Pathologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Département de Pathologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut Claudius-Regaud [IUCT, Toulouse], Institut Universitaire du Cancer Toulouse - Oncopôle (IUCT), Département de Neurochirurgie [CHU Toulouse], Département de Neurochirurgie[Lille], Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU 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 Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Département de Pathologie [Centre Médical Universitaire Montpellier], Centre Médical Universitaire Montpellier - CMUM, 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), Département d'Oncopédiatrie [CHU Toulouse], Hopp Children's Cancer Center Heidelberg [Heidelber, Germany] (KITZ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)-Heidelberg University Hospital [Heidelberg], Division of Pediatric Neurooncology [Heidelberg, Germany], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)-German Cancer Consortium [Heidelberg] (DKTK), Département de Pathologie [CHU Marseille], CHU Marseille, Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), D. Jones is supported by funding for the Everest Centre for Paediatric Low- Grade Brain Tumour Research through the Brain Tumour Charity (UK). We are grateful to Karen Silva for her help in handling tumor samples from the different pathological departments. Samples from Marseille were retrieved from the AP-HM tumor bank AC 2017:1786. Samples from Toulouse were retrieved from the CHU de Toulouse tumor bank BB-0033-00014., Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Neurochirurgie [CHU Toulouse], Pôle Neurosciences [CHU Toulouse], 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), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Sercice Hématologie, immunologie et oncologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Bernardo, Elizabeth, 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), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), 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), 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), Université de Toulouse (UT), Design and Application of Innovative Local Treatments in Glioblastoma (CRCINA - Département NOHMAD - Equipe 17), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre de recherche Jean-Pierre Aubert-Neurosciences et Cancer, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Institut pour la Recherche sur le Cancer de Lille (U837 INSERM - IRCL), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche Jean-Pierre AUBERT - Neurosciences et Cancer -JPArc [Lille], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopp Children's Cancer Center at the NCT Heidelberg - KiTZ [Heidelber, Germany]g, Centre de Recherche en Cancérologie de Toulouse ( CRCT ), Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Design and Application of Innovative Local Treatments in Glioblastoma ( CRCINA - Département NOHMAD - Equipe 17 ), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers ( CRCINA ), Université d'Angers ( UA ) -Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche en Santé de l'Université de Nantes ( IRS-UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Université d'Angers ( UA ) -Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche en Santé de l'Université de Nantes ( IRS-UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre hospitalier universitaire d'Angers ( CHU Angers ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, Institut pour la Recherche sur le Cancer de Lille ( U837 INSERM - IRCL ), Institut pour la recherche sur le cancer de Lille [Lille] ( IRCL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre de Recherche Jean-Pierre AUBERT - Neurosciences et Cancer -JPArc [Lille], Institut de pharmacologie et de biologie structurale ( IPBS ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Universitaire du Cancer Toulouse - Oncopôle ( IUCT ), Centre Hospitalier Universitaire de Toulouse - CHU Toulouse (FRANCE), Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Toulouse Neuro Imaging Center ( ToNIC ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Purpan - Centre Hospitalier Universitaire (CHU) de Toulouse-Université Toulouse III - Paul Sabatier, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs ( INM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), German Cancer Research Center ( DKFZ ) -German Cancer Consortium - DKTK [Heidelberg, Germany], Institut de neurophysiopathologie ( INP ), and Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: 0301 basic medicine, Adult, Male, DNA Copy Number Variations, Kruppel-Like Transcription Factors, Locus (genetics), [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Pathology and Forensic Medicine, Ganglioglioma, Fusion gene, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Glioma, medicine, Biomarkers, Tumor, Humans, Copy-number variation, Child, In Situ Hybridization, Fluorescence, Research Articles, Sanger sequencing, Brain Neoplasms, General Neuroscience, Methylation, DNA Methylation, medicine.disease, Neoplasms, Neuroepithelial, 3. Good health, Repressor Proteins, 030104 developmental biology, Fusion transcript, Cancer research, symbols, Female, Neurology (clinical), Gene Fusion, RNA-Binding Protein EWS, 030217 neurology & neurosurgery
Abstract: International audience; We investigated the challenging diagnostic case of a ventricular cystic glioneuronal tumor with papillary features, by RNA sequencing using the Illumina TruSight RNA Fusion panel. We did not retrieve the SLC44A1-PRKCA fusion gene specific for papillary glioneuronal tumor, but an EWSR1-PATZ1 fusion transcript. RT-PCR followed by Sanger sequencing confirmed the EWSR1-PATZ1 fusion. It matched with canonic EWSR1 fusion oncogene, juxtaposing the entire N terminal transcriptional activation domain of EWSR1 gene and the C terminal DNA binding domain of a transcription factor gene, PATZ1. PATZ1 protein belongs to the BTB-ZF (broad-complex, tramtrack and bric-à-brac -zinc finger) family. It directly regulates Pou5f1 and Nanog and is essential to maintaining stemness by inhibiting neural differentiation. EWSR1-PATZ1 fusion is a rare event in tumors: it was only reported in six round cell sarcomas and in three gliomas of three exclusively molecular studies. The first reported glioma was a BRAF[V600E] negative ganglioglioma, the second a BRAF[V600E] negative glioneuronal tumor, not otherwise specified, and the third, very recently reported, a high grade glioma, not otherwise specified. In our study, forty BRAF[V600E] negative gangliogliomas were screened by FISH using EWSR1 break-apart probes. We performed methylation profiling for the index case and for seven out of the ten FISH positive cases. The index case clustered apart from other pediatric low grade glioneuronal entities, and specifically from the well-defined ganglioglioma methylation group. An additional pediatric intraventricular ganglioglioma clustered slightly more closely with ganglioglioma, but showed differences from the main ganglioglioma group and similarities with the index case. Both cases harbored copy number variations at the PATZ1 locus. EWSR1-PATZ1 gene fusion might define a new type of glioneuronal tumors, distinct from gangliogliomas.
Published: 2019

14. Thrombotic microangiopathy associated with gemcitabine use: Presentation and outcome in a national French retrospective cohort

Author: Julien Mancini, Pascale Poullin, Joëlle Micallef, Florence Daviet, Marion Sallée, Paul Coppo, Aurélie Grandvuillemin, Franck Rouby, Noémie Jourde-Chiche, Renaud Sabatier, Steven Grangé, Véronique Frémeaux-Bacchi, Bertrand Pourroy, Stéphane Burtey, Florence Duffaud, Julie Moussi-Frances, Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )-Assistance Publique - Hôpitaux de Marseille (APHM), Centre régional de pharmacovigilance de Marseille [CHU de Marseille], CHU Marseille, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d\'hémaphérèse, Hôpital de la Conception, APHM, Marseille, France, Service d'hémaphérèse, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chirurgie urologique et transplantation rénale [Hôpital de la Conception - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Recherche en Cancérologie de Marseille (CRCM), 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), Service Pharmacie [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Régional de Pharmacovigilance, de Renseignement sur le Médicament et de Pharmaco épidémiologie de Bourgogne [Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de réanimation médicale [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Saint-Antoine [APHP], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), 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)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), 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)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), 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), Service de réanimation médicale [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Assistance Publique - Hôpitaux de Marseille (APHM), CHU Marseille-Assistance Publique-Hôpitaux de Marseille (AP-HM), and Prémilleux, Annick
Subjects: Male, medicine.medical_specialty, Antimetabolites, Antineoplastic, Thrombotic microangiopathy, medicine.medical_treatment, [SDV]Life Sciences [q-bio], chemotherapy, 030226 pharmacology & pharmacy, Gastroenterology, Deoxycytidine, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Neoplasms, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Adverse effect, Dialysis, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Pharmacology, adverse drug reactions, business.industry, Thrombotic Microangiopathies, Acute kidney injury, Retrospective cohort study, Original Articles, Eculizumab, Middle Aged, medication safety, medicine.disease, Gemcitabine, 3. Good health, [SDV] Life Sciences [q-bio], acute kidney injury, pharmacovigilance, Female, Fresh frozen plasma, France, business, medicine.drug
Abstract: International audience; Aims Gemcitabine has been associated with thrombotic microangiopathy (TMA). We conducted a national retrospective study of gemcitabine-associated TMA (G-TMA). Methods From 1998 to 2015, all cases of G-TMA reported to the French Pharmacovigilance Network and the French TMA Reference Center, and cases explored for complement alternative pathway abnormalities, were analysed. Results G-TMA was diagnosed in 120 patients (median age 61.5 years), after a median of 210 days of treatment, and a cumulative dose of 12 941 mg m(-2). Gemcitabine indications were: pancreatic (52.9%), pulmonary (12.6%) and breast (7.6%) cancers, metastatic in 34.2% of cases. Main symptoms were oedema (56.7%) and new-onset or exacerbated hypertension (62.2%). Most patients presented with haemolytic anaemia (95.6%) and thrombocytopenia (74.6%). Acute kidney injury was reported in 97.4% and dialysis was required in 27.8% of patients. Treatment consisted of: plasma exchange (PE; 39.8%), fresh frozen plasma (21.4%), corticosteroids (15.3%) and eculizumab (5.1%). A complete remission of TMA was obtained in 42.1% of patients and haematological remission in 23.1%, while 34.7% did not improve. The survival status was known for 52 patients, with 29 deaths (54.7%). Patients treated with PE, despite a more severe acute kidney injury, requiring dialysis more frequently, displayed comparable rates of remission, but with more adverse events. No abnormality in complement alternative pathway was documented in patients explored. Conclusion This large cohort confirms the severity of G-TMA, associated with severe renal failure and death. Oedema and hypertension could be monitored in patients treated with gemcitabine to detect early TMA. The benefit of PE or eculizumab deserves further investigation.
Published: 2018

15. Treatment of voluminous and complicated superficial slow-flow vascular malformations with sirolimus (PERFORMUS): protocol for a multicenter phase 2 trial with a randomized observational-phase design

Author: Valérie Gissot, Laurent Guibaud, Groupe de Recherche de la Société Française de Dermatologie Pédiatrique, Jean-Baptiste Woillard, Christine Chiaverini, Sébastien Barbarot, Catherine Droitcourt, Stéphanie Mallet, Bruno Giraudeau, Juliette Mazereeuw-Hautier, Dominique Goga, Ludovic Martin, Gérard Lorette, Jérôme Rollin, Denis Herbreteau, Didier Bessis, Yves Gruel, Baptiste Morel, Annabel Maruani, Sophie Leducq, Annie-Pierre Jonville-Béra, Anne Le Touze, Elsa Tavernier, Pierre Vabres, Olivia Boccara, Sophie Blaise, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours-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), Service de dermatologie (CHRU de Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Clinical Investigation Center - INSERM 1415, CHU Necker - Enfants Malades [AP-HP], Centre de Référence National des Maladies Génétiques à Expression Cutanée (MAGEC), Service de Dermatologie, Département de dermatologie [CHU de Montpellier], Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de dermatologie (CHU de Toulouse), CHU Toulouse [Toulouse], Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Clinique de Médecine Vasculaire, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Service de Dermatologie [Rennes], CHU Pontchaillou [Rennes], Département de dermatologie, CHU Marseille, CHU Marseille, Service de Dermatologie [CHU Angers] (PXE - le PseudoXanthome Elastique), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de pharmacologie clinique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours, Service de neuroradiologie [Tours], Service de chirurgie maxillo-faciale [CHRU Tours], Département de chirurgie pédiatrique [Clocheville University Hospital, Tours], CHRU Clocheville, CIC 1415 Centre d’Investigation Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Radiologie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), 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), Service de dermatologie [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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), CHU Dijon, Centre Hospitalier Universitaire [Grenoble] (CHU), PRES Université Nantes Angers Le Mans (UNAM), Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, Université de Tours (UT), Groupe de Recherche de la Societé Française de Dermatologie Pédiatrique., Rollin, Jérôme, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Pediatrics, Time Factors, Vascular Malformations, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Study Protocol, 0302 clinical medicine, Quality of life, Sclerotherapy, Clinical endpoint, Multicenter Studies as Topic, Pharmacology (medical), Child, Lymphatic malformations, Children, Mammalian target of rapamycin inhibitors, Randomized Controlled Trials as Topic, lcsh:R5-920, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Age Factors, Vascular anomalies, Magnetic Resonance Imaging, 3. Good health, Lymphangiogenesis, Natural history, [SDV] Life Sciences [q-bio], Observational Studies as Topic, Treatment Outcome, 030220 oncology & carcinogenesis, Venous malformations, Female, France, lcsh:Medicine (General), Blood Flow Velocity, medicine.drug, medicine.medical_specialty, Adolescent, 03 medical and health sciences, Clinical Trials, Phase II as Topic, 030225 pediatrics, Coronary Circulation, medicine, Humans, Protein Kinase Inhibitors, Sirolimus, business.industry, Clinical trial, Randomized placebo-phase design, Observational study, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Slow-flow superficial vascular malformations (VMs) are rare congenital anomalies that can be responsible for pain and functional impairment. Currently, we have no guidelines for their management, which can involve physical bandages, sclerotherapy, surgery, anti-inflammatory or anti-coagulation drugs or no treatment. The natural history is progressive and worsening. Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that acts as a master switch in cell proliferation, apoptosis, metabolism and angio/lymphangiogenesis. Sirolimus directly inhibits the mTOR pathway, thereby inhibiting cell proliferation and angio/lymphangiogenesis. Case reports and series have reported successful use of sirolimus in children with different types of vascular anomalies, with heterogeneous outcomes. Objective The objective of this trial is to evaluate the efficacy and safety of sirolimus in children with complicated superficial slow-flow VMs. Methods/design This French multicenter randomized observational-phase, phase 2 trial aims to include 50 pediatric patients 6 to 18 years old who have slow-flow (lymphatic, venous or lymphatico-venous) voluminous complicated superficial VM. Patients will be followed up for 12 months. All patients will start with an observational period (no treatment). Then at a time randomly selected between month 4 and month 8, they will switch to the experimental period (switch time), when they will receive sirolimus until month 12. Each child will undergo MRI 3 times: at baseline, at the switch time, and at month 12. For both periods (observational and treatment), we will calculate the relative change in volume of the VM divided by the study period duration. This relative change weighted by the study period duration will constitute the primary endpoint. VM will be measured by MRI images, which will be centralized and interpreted by the same radiologist who will be blinded to the study period. Hence, each patient will be his/her own control. Secondary outcomes will include assessment of safety and efficacy by viewing standardized digital photographs and according to the physician, the patient or proxy; impact on quality of life; and evolution of biological makers (coagulation factors, vascular endothelial growth factor, tissue factor). Discussion The main benefit of the study will be to resolve uncertainty concerning the efficacy of sirolimus in reducing the volume of VMs and limiting related complications and the safety of the drug in children with slow-flow VMs. This trial design is interesting in these rare conditions because all included patients will have the opportunity to receive the drug and the physician can maintain it after the end of the protocol if is found efficient (which would not be the case in a classical cross-over study). Trial registration ClinicalTrials.gov Identifier: NCT02509468, first received: 28 July 2015. EU Clinical Trials Register EudraCT Number: 2015-001096-43. Electronic supplementary material The online version of this article (10.1186/s13063-018-2725-1) contains supplementary material, which is available to authorized users.
Published: 2018

16. Adverse consequences of low-dose methotrexate medication errors: data from French poison control and pharmacovigilance centers

Author: Romain Torrents, David Boels, Anne Marie Patat, Antoine Villa, Thierry Vial, Delphine Castellan, Hélène Theophile, Behrouz Kassai, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hospices Civils de Lyon (HCL), Centres antipoison et de toxicovigilance (CAPTV Angers), Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), CHU Marseille-Assistance Publique-Hôpitaux de Marseille (AP-HM), Centre antipoison et de toxicovigilance (Paris) (CAPTV Paris), Université Paris Diderot - Paris 7 (UPD7)-Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, CHU Bordeaux [Bordeaux], Centre antipoison et de toxicovigilance (Marseille) (CAPTV Marseille), Assistance Publique - Hôpitaux de Marseille (APHM), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre Antipoison et Toxicovigilance du Grand Ouest (Angers) (CAPTV Angers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, and CCSD, Accord Elsevier
Subjects: Male, Pediatrics, Databases, Factual, Poison control, Administration, Oral, Arthritis, Rheumatoid, Pharmacovigilance, 0302 clinical medicine, Medicine, Medication Errors, 030212 general & internal medicine, Aged, 80 and over, Cumulative dose, Age Factors, Medication error, Middle Aged, 3. Good health, Survival Rate, Female, France, medicine.symptom, medicine.drug, Adult, medicine.medical_specialty, Poison Control Centers, Drug-Related Side Effects and Adverse Reactions, Context (language use), Asymptomatic, Risk Assessment, Drug Administration Schedule, Drug toxicity, 03 medical and health sciences, Sex Factors, Rheumatology, Humans, Dosing, Mortality, Adverse effect, Aged, 030203 arthritis & rheumatology, Dose-Response Relationship, Drug, business.industry, Logistic Models, Methotrexate, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Multivariate Analysis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Follow-Up Studies
Abstract: Objective The objectives of this study are to carefully describe the context of methotrexate medication errors, to details medical consequences and management approaches, and to determine the rate of fatal outcome. Methods Data on methotrexate medication errors were obtained from the French network of poison control and pharmacovigilance centres, which collected and documented reported drug-induced adverse effects. Cases were included if the intake was more than 2-fold the intended weekly dose or a weekly cumulative dose ≥ 30 mg and a follow-up of at least 4 days after the last dose. Data were analysed for demographics, treatment indication, prescribed dose, drug interactions, clinical complications and medical outcomes. Results Seventy four patients were included. The causes of methotrexate errors resulted from an erroneous prescription renewal (23.3%), incomprehensiveness of the weekly schedule by patients or at-home caregivers (56.2%) and administration of a wrong dose by a health care professional (20.5%). Of the 70 patients who took methotrexate daily, the mean daily dose received over the whole duration of the error was 9.6 ± 4.1 mg (range 2.5–22.5) with a mean duration of the error of 11.7 ± 12.2 days (range 2 to 90). Thirteen (18%) patients remained asymptomatic and 61 (82%) developed complications of which 46 (62.2%) were severe. Nine (14.8%) patients died within 11 to 45 days after the first dosing error. Compared to patients with no or mild symptoms, those with severe symptoms were more likely to be older (75.6 ± 10.8 vs. 69.5 ± 12.9 years) and to be exposed to a higher cumulative dose (94.8 ± 46.2 vs. 68.0 ± 45.7 mg). Conclusions This study confirms that dosing errors with methotrexate can be lethal and persisted despite several warnings from drug agencies. Further measures are awaited from the European Medicine Agency.
Published: 2018

17. Sperm aneuploidy and DNA fragmentation in unexplained recurrent pregnancy loss: a multicenter case-control study

Author: Camille Esquerré-Lamare, Florence Bretelle, Louis Bujan, Lucie Chansel Debordeaux, Laetitia Monteil, Gilles Karsenty, Jessika Moreau, Jeanne Perrin, François Isus, Marie Walschaerts, Aline Papaxanthos-Roche, Groupe de recherche en fertilité humaine ( GRFH), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, CECOS Groupe d'Activité de Médecine de la Reproduction, [CHU Toulouse], France, CECOS Service Biologie de la Reproduction, [CHU Bordeaux], Service de Gynécologie-Obstétrique, CHU Marseille, Hôpital Nord, AP-HM, 13015 Marseille, France., CHU Marseille, Andrologie, Groupe d’Activité de Médecine de la Reproduction, [CHU Toulouse], Toulouse, France., Service d'urologie et de transplantation rénale, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM), Service de Génétique Médicale, CHU Toulouse, Toulouse, France., Centre Clinico-Biologique d’Assistance Médicale à la Procréation - CECOS [Hôpital de la Conception - APHM], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UMR237-Aix Marseille Université (AMU)-Avignon Université (AU), Université de Toulouse (UT)-Université de Toulouse (UT), Groupe d'Activité de Médecine de la Reproduction [CHU Toulouse] (CECOS Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service Génétique Médicale [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], and Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Infertility, Urology, media_common.quotation_subject, Aneuploidy, Fertility, Context (language use), Biology, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Sperm aneuploidy, Andrology, 03 medical and health sciences, 0302 clinical medicine, Fausses couches à répétition inexpliquées, aneuploïdie du spermatozoïde, fragmentation de l’ADN du sperme, facteur masculin, medicine, Unexplained recurrent pregnancy loss, Sperm motility, media_common, lcsh:R5-920, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, urogenital system, Fluorescence in situ hybridization, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, medicine.disease, Sperm, Sperm DNA fragmentation, 030104 developmental biology, Reproductive Medicine, DNA fragmentation, lcsh:Medicine (General), [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article
Abstract: Recurrent pregnancy loss (RPL) is defined as the loss of at least three pregnancies in the first trimester. Although the most common cause is embryo aneuploidy, and despite female checkup and couple karyotyping, in about 50% of cases RPL remain unexplained. Male implication has little been investigated and results are discordant. In this context, we conducted a multi-center prospective case-control study to investigate male gamete implication in unexplained RPL.A total of 33 cases and 27 controls were included from three university hospitals. We investigated environmental and family factors with a detailed questionnaire and andrological examination, sperm characteristics, sperm DNA/chromatin status using the sperm chromatin structure assay (SCSA) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and sperm aneuploidy using fluorescence in situ hybridization (FISH). The Mann-Whitney test and the Wilcoxon or Fisher exact tests were used. A non-parametric Spearman correlation was performed in order to analyze the relationship between various sperm parameters and FISH and sperm DNA fragmentation results.We found significant differences between cases and controls in time to conceive, body mass index (BMI), family history of infertility and living environment. In cases, total sperm motility and the percentage of morphologically normal spermatozoa were significantly decreased. No difference was found between cases and controls in sperm DNA fragmentation or chromatin integrity. In cases, spermatozoa with aneuploidy, hyperhaploidy and chromosome 18 disomy were significantly increased.This prospective case-control study is one of the largest to examine environmental factors, sperm characteristics, sperm DNA fragmentation and chromatin, and chromosome anomalies in spermatozoa in relation to unexplained recurrent pregnancy loss. The originality of our study lies in the comprehensive andrological examination and search for risk factors and fertility history. Further studies are needed to confirm the links between unexplained RPL and a male family history of infertility or miscarriages. The increased sperm aneuploidy observed in unexplained RPL supports a male etiology. These data pave the way for further studies to demonstrate the value of preimplantation genetic screening in men with increased sperm aneuploidy whose partners experience unexplained RPL.Les fausses couches à répétition (FCR) sont définies lorsqu’au moins trois fausses couches ont eu lieu au cours du premier trimestre. Bien que la cause la plus fréquente soit l’aneuploïdie embryonnaire, et malgré un bilan chez la femme et un caryotype du couple, dans environ 50% des cas, les FCR restent inexpliquées. L’implication masculine a été peu étudiée et les résultats restent discordants. Ainsi, nous avons réalisé une étude cas-témoins prospective et multicentrique afin d’investiguer l’implication du gamète mâle dans les FCR inexpliquées.Un total de 33 cas et de 27 témoins ont été inclus recrutés au sein de trois hôpitaux universitaires. Nous avons étudié les facteurs environnementaux et familiaux à partir d’un questionnaire détaillé ainsi que les données de l’examen andrologique, les caractéristiques du sperme, la fragmentation de l’ADN et la chromatine du spermatozoïde en utilisant le sperm chromatine structure assay (SCSA) et le test du TUNEL, ainsi que l’aneuploïdie des spermatozoïdes grâce à la méthode d’hybridation in situ de sonde chromosomique (FISH). Le test de Mann-Whitney et les tests exacts de Wilcoxon ou de Fisher ont été utilisés. Une corrélation de Spearman non-paramétrique a été réalisée afin d’analyser la relation entre les divers paramètres de sperme et les résultats de fragmentation d’ADN du sperme et les résultats de la FISH.Nous avons trouvé des différences significatives entre les cas et les témoins pour le délai de conception, l’indice de masse corporelle (IMC), les antécédents familiaux d’infertilité et le milieu de vie. Chez les cas, la mobilité totale des spermatozoïdes et le pourcentage de spermatozoïdes normaux étaient significativement diminués. Aucune différence n’a été trouvée entre les cas et les témoins concernant la fragmentation de l’ADN des spermatozoïdes ou l’intégrité de la chromatine. Chez les cas, la fréquence des spermatozoïdes présentant une aneuploïdie, une hyperhaploïdie et une disomie du chromosome 18 étaient significativement augmentée.Cette étude cas-témoins prospective est. l’une des plus importantes ayant investigué à la fois les facteurs environnementaux, les caractéristiques des spermatozoïdes, la fragmentation et la chromatine de l’ADN des spermatozoïdes et les anomalies chromosomiques des spermatozoïdes en rapport avec les fausses couches à répétition inexpliquée. L’originalité de notre étude réside dans l’examen andrologique complet et la recherche des facteurs de risque et des antécédents reproductifs. D’autres études sont nécessaires pour confirmer les liens entre les FCR inexpliquées et les antécédents familiaux masculins d’infertilité ou de fausses couches. L’augmentation de l’aneuploïdie des spermatozoïdes observée chez les cas présentant des FCR inexpliquées plaide en faveur d’une étiologie masculine. Ces données ouvrent la voie à d’autres études pour démontrer l’utilité d’un dépistage génétique préimplantatoire chez les hommes présentant une augmentation de l’aneuploïdie des spermatozoïdes dont les partenaires présentent des FCR inexpliquées.
Published: 2018

18. Efficacy of Immunotherapy in Patients with Metastatic Mucosal or Uveal Melanoma

Author: Mona Amini-Adle, Pierre Marcant, Yannick Le Corre, Caroline Dutriaux, Nora Kramkimel, Anne Bénédicte Duval Modeste, N. Litrowski, C. Lesage, Nicolas Meyer, Amir Khammari, Caroline Gaudy-Marqueste, C. Mignard, Aurélie Deschamps Huvier, Eve Maubec, Thierry Lesimple, Laurent Mortier, Florence Brunet-Possenti, L. Visseaux, Géraldine Jeudy, A. Stefan, Marie-Françoise Avril, Sabiha Trabelsi, Henri Montaudié, François Aubin, Pascal Joly, Laurent Machet, André Gillibert, Marie-Thérèse Leccia, Jean-Philippe Arnault, Nathalie Beneton, E. Wierzbicka-Hainaut, Dan Lipsker, Service de dermatologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), CHU Bordeaux [Bordeaux], Clinical and Translational Research in Skin Cancer (CRCINA-ÉQUIPE 2), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), 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)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-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)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], Hôpital Claude Huriez [Lille], CHU Lille, Département d'oncologie médicale [Rennes], CRLCC Eugène Marquis (CRLCC), Département de dermatologie, CHU Marseille, CHU Marseille, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de dermatologie (CHRU de Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Département de dermatologie, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Hôpital Saint-Jacques-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Département de la santé publique [CHU Strasbourg], CHU Strasbourg, Centre Hospitalier Le Mans (CH Le Mans), Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de dermatologie [CHU d'Amiens-Picardie], CHU Amiens-Picardie, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de dermatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de Dermatologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Dermatology Department, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Département Pluridisciplinaire de Médecine, Dermatologie, CHU Grenoble-Hôpital Michallon, Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Paris Diderot - Paris 7 (UPD7)-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), Hôpital Saint-André, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université Paris Descartes - Paris 5 (UPD5), Hôpital de la Timone [CHU - APHM] (TIMONE), Université Francois Rabelais [Tours], Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire [Grenoble] (CHU), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hôpital Avicenne [AP-HP], Université Paris 13 (UP13), PRES Université Nantes Angers Le Mans (UNAM), Université de Strasbourg (UNISTRA), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Groupe Hospitalier du Havre Hôpital Jacques Monod (MONTIVILLIERS) (GHH), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), and TAN, Yossan-Var
Subjects: 0301 basic medicine, medicine.medical_specialty, Article Subject, medicine.medical_treatment, Gastroenterology, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, medicine, Stage (cooking), Chemotherapy, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Melanoma, Mucosal melanoma, Retrospective cohort study, Immunotherapy, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cohort, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Research Article
Abstract: Background: The objective was to assess the response rate and survival of patients with metastatic mucosal melanoma (MM) and uveal melanoma (UM) treated with anti-CTLA-4 or anti-PD-1 monoclonal antibodies (mAbs).Methods: A multicenter retrospective study was performed in 25 dermatology departments in France. All patients with stage III-C to IV MM or UM who were treated with anti-CTLA-4 or anti-PD-1 mAbs between 2008 and 2016 were included and compared after adjustment for main prognostic factors with a second cohort of patients treated with chemotherapy. Tumor response was evaluated according to RECIST v. 1.1 criteria at Week 12.Results: Four-hundred-and-thirty-nine patients were included, 229 MM (151 immunotherapy, 78 chemotherapy) and 210 UM (100 immunotherapy, 110 chemotherapy). Response rates of MM patients treated with immunotherapy were 18/151 (11.9%; 95% CI:7.2%-18.2%), versus 11/78 (14.1%, 95% CI:7.3%-23.8%) in patients treated with chemotherapy (p=0.87). No tumor response was observed in UM patients treated with immunotherapy, versus 4/110 responses (3.6%, 95% CI:1.0-9.0%) in patients treated with chemotherapy (p=0.15). The adjusted overall survival (OS) of MM patients treated with immunotherapy was longer than that of patients treated with chemotherapy HR=0.62 (95% CI: 0.43-0.91), p=0.014, with an unadjusted median OS of 15.97 months [interquartile range (IQR)=6.89-27.11] and 8.82 months [IQR=5.02-14.92], respectively. The adjusted OS of UM patients treated with immunotherapy was not significantly different from that of patients treated with chemotherapy (HR=0.98, 95% CI: 0.66-1.44) p=0.92, with an unadjusted median OS of 13.38 months [IQR=6.03-29.57] and 11.02 months [IQR=6.13-23.93], respectively.Conclusion: Immunotherapy significantly improves OS for MM. The prognosis of metastatic UM remains poor., Immunotherapy significantly improves OS for MM. The prognosis of metastatic UM remains poor.
Published: 2018

19. Dipeptidyl peptidase IV inhibitors, a risk factor for bullous pemphigoid: Retrospective multicenter case-control study from France and Switzerland

Author: Marie-Aleth Richard, Philippe Berbis, M. Benzaquen, Simone Cazzaniga, Luca Borradori, Laurence Feldmeyer, René Valéro, Hôpital Nord [CHU - APHM], Universität Bern [Bern], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), 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), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Département de dermatologie, CHU Marseille, CHU Marseille, Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Centre recherche en CardioVasculaire et Nutrition (C2VN), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Universität Bern [Bern] (UNIBE)
Subjects: Male, bullous pemphigoid, Dipeptidyl peptidase-4 inhibitor, Tertiary Care Centers, 030207 dermatology & venereal diseases, 0302 clinical medicine, Adrenal Cortex Hormones, Pemphigoid, Bullous, Vildagliptin, gliptin, diabetes, Incidence (epidemiology), Incidence, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Prognosis, 3. Good health, risk factor, dipeptidyl peptidase-4 inhibitor, 030220 oncology & carcinogenesis, Female, France, Switzerland, medicine.drug, Adult, medicine.medical_specialty, case-control study, Dermatology, Risk Assessment, 03 medical and health sciences, Age Distribution, Internal medicine, medicine, Humans, Risk factor, Sex Distribution, Aged, Retrospective Studies, Dipeptidyl-Peptidase IV Inhibitors, business.industry, Case-control study, Retrospective cohort study, Odds ratio, Confidence interval, Logistic Models, Diabetes Mellitus, Type 2, Case-Control Studies, Multivariate Analysis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience; Background: Case reports have suggested an association between dipeptidyl peptidase-4 inhibitors (DPP4is) and development of bullous pemphigoid (BP).Objective: To evaluate the association between DPP4i treatment and development of BP.Methods: We conducted a retrospective 1:2 case-control study, comparing case patients with diabetes and BP with age- and sex-matched control patients with diabetes issued from Swiss (Bern) and French (Marseille) dermatologic departments from January 1, 2014, to July 31, 2016.Results: We collected 61 case patients with diabetes and BP and 122 controls. DPP4is were associated with an increased risk for development of BP (adjusted odds ratio, 2.64; 95% confidence interval, 1.19-5.85; P = .02), with vildagliptin showing the highest adjusted odds ratio (3.57 [95% confidence interval, 1.07-11.84; P = .04]). Stratified analysis showed a stronger association in males and patients age 80 years or older. DPP4i withdrawal and the initiation of first-line treatments led to clinical remission in 95% of cases.Limitations: This was a retrospective study in tertiary referral hospitals. We focused the analysis on DPP4i intake, without analyzing the potential isolated effect of metformin.Conclusions: DPP4is, especially vildagliptin, are associated with an increased risk for development of BP. Their use needs to be carefully evaluated, particularly in high-risk patients, such as males and those age 80 years or older.
Published: 2018

20. Quantification of HPV16 E6/E7 mRNA Spliced Isoforms Viral Load as a Novel Diagnostic Tool for Improving Cervical Cancer Screening

Author: Céline Loubatier, Philippe Halfon, Valérie Giordanengo, Anne Plauzolles, Xavier Carcopino, Sébastien Vitale, Guillaume Penaranda, Hacène Khiri, Claire Camus, Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UMR237-Aix Marseille Université (AMU)-Avignon Université (AU), Service de Gynécologie-Obstétrique, CHU Marseille, Hôpital Nord, AP-HM, 13015 Marseille, France., CHU Marseille, Microbes évolution phylogénie et infections (MEPHI), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS), ALPHABIO - Laboratoire de biologie médicale, Bases, Corpus, Langage (UMR 7320 - UCA / CNRS) (BCL), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Gene isoform, high risk human papillomaviruses (HPVs) infection, cervical cancer, lcsh:Medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cervical intraepithelial neoplasia, Article, 03 medical and health sciences, 0302 clinical medicine, medicine, Pap test, Cervical cancer, Messenger RNA, medicine.diagnostic_test, business.industry, lcsh:R, qRT-PCR, General Medicine, medicine.disease, Molecular biology, 3. Good health, Reverse transcription polymerase chain reaction, 030104 developmental biology, Real-time polymerase chain reaction, 030220 oncology & carcinogenesis, grade 2 or higher cervical intraepithelial neoplasia, HPV16 E6/E7 mRNA viral loads, business, Viral load, diagnostic tool
Abstract: High-risk human papillomaviruses (HPVs) have been identified as the main contributors to cervical cancer. Despite various diagnostic tools available, including the predominant Papanicolaou test (Pap test), technical limitations affect the efficiency of cervical cancer screening. The aim of this study was to evaluate the diagnostic performance of spliced HPV16 E6/E7 mRNA viral loads (VL) for grade 2 or higher cervical intraepithelial neoplasia diagnosis. A new dedicated (quantitative reverse transcription polymerase chain reaction) qRT-PCR assay was developed, allowing selective quantification of several HPV16 E6/E7 mRNA: Full length (FL) with or without all or selected spliced forms (total E6/E7 mRNA corresponding to SP + E6^E7 mRNA (T), + spliced E6/E7 mRNA containing intact E7 ORF (SP), and E6/E7 mRNA containing disrupted E6 and E7 ORFs calculated by the following subtraction T-SP (E6^E7)). Twenty HPV16 DNA and mRNA positive uterine cervical smears representative of all cytological and histological stages of severity were tested. We have shown that all E6/E7 mRNA isoforms expression levels were significantly increased in high grade cervical lesions. Statistical analysis demonstrated that the SP-E6/E7 VL assay exhibited: (i) The best diagnostic performance for identification of both cervical intraepithelial neoplasia (CIN)2+ (90% (56&ndash, 100) sensitivity and specificity) and CIN3+ (100% (72&ndash, 100) sensitivity and 79% (49&ndash, 95) specificity) lesions, (ii) a greater sensitivity compared to the Pap test for CIN2+ lesions detection (80% (44&ndash, 97)), (iii) a predictive value of the histological grade of cervical lesions in 67% of atypical squamous cells of unknown significance (ASC-US) and 100% of low-grade (LSIL) patients. Overall, these results highlight the value of SP-E6/E7 mRNA VL as an innovative tool for improving cervical cancer screening.
Published: 2018

21. A novel anti-CD146 antibody specifically targets cancer cells by internalizing the molecule

Author: Nollet, Marie, STALIN, JIMMY, Moyon, Anaïs, Traboulsi, Wael, Essaadi, Amel, Robert, Stéphane, Malissen, Nausicaa, Bachelier, Richard, Daniel, Laurent, Foucault-Bertaud, Alexandrine, Gaudy-Marqueste, Caroline, Lacroix, Romaric, Leroyer, Aurélie, Guillet, Benjamin, Bardin, Nathalie, Dignat-George, Francoise, Blot-Chabaud, Marcel, Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie de l'Endothelium, Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix-Marseille Université - Faculté de pharmacie (AMU PHARM), Aix Marseille Université (AMU), Département de dermatologie [CHU de Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital de la Timone [CHU - APHM] (TIMONE), Département de dermatologie, CHU Marseille, CHU Marseille, Laboratoire d'Immunologie [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), and Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )
Subjects: therapy, PET, CD146, antibody, [SDV]Life Sciences [q-bio], cancer, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; CD146 is an adhesion molecule present on many tumors (melanoma, kidney, pancreas, breast, ...). In addition, it has been shown to be expressed on vascular endothelial and smooth muscle cells. Generating an antibody able to specifically recognize CD146 in cancer cells (designated as tumor CD146), but not in normal cells, would thus be of major interest for targeting tumor CD146 without affecting the vascular system. We thus generated antibodies against the extracellular domain of the molecule produced in cancer cells and selected an antibody that specifically recognizes tumor CD146. This antibody (TsCD146 mAb) was able to detect CD146-positive tumors in human biopsies and in vivo, by PET imaging, in a murine xenograft model. In addition, TsCD146 mAb antibody was able to specifically detect CD146-positive cancer microparticles in the plasma of patients. TsCD146 mAb displayed also therapeutic effects since it was able to reduce the growth of human CD146-positive cancer cells xenografted in nude mice. This effect was due to a decrease in the proliferation and an increase in the apoptosis of CD146-positive cancer cells after TsCD146-mediated internalization of the cell surface CD146. Thus, TsCD146 mAb could be of major interest for diagnostic and therapeutic strategies against CD146-positive tumors in a context of personalized medicine. www.impactjournals.com/oncotarget/
Published: 2017

22. Cognitive and imaging markers in non-demented subjects attending a memory clinic: study design and baseline findings of the MEMENTO cohort

Author: Dufouil , Carole, Dubois , Bruno, Vellas , Bruno, Pasquier , Florence, Blanc , Frédéric, Hugon , Hugo, Hanon , Olivier, Dartigues , Jean-François, Harston , Sandrine, Gabelle , Audrey, Ceccaldi , Mathieu, Beauchet , Olivier, Krolak-Salmon , Pierre, David , David, Rouaud , Olivier, Godefroy , Olivier, Belin , Catherine, Rouch , Isabelle, Auguste , Nicolas, Wallon , David, Benetos , Athanase, Pariente , Jeremie, Paccalin , Marc, Moreaud , Olivier, Hommet , Caroline, Sellal , François, Boutoleau-Bretonnière , Claire, Jalenques , Isabelle, Gentric , Armelle, Vandel , Pierre, Azouani , Chabha, Fillon , Ludovic, Fischer , Clara, Savarieau , Helen, Operto , Grégory, Bertin , Hugo, Chupin , Marie, Bouteloup , Vincent, Habert , Marie-Odile, Mangin , Jean-François, Chêne , Geneviève, Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, 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 [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), 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), Hématopoïèse normale et pathologique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Laboratoire de physique de la matière condensée (LPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Groupe hospitalier Broca, CHU Bordeaux [Bordeaux], Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Service de neurologie et de neuropsychologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire de Psychologie des Pays de la Loire (LPPL), Université d'Angers (UA)-Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN), Hospices Civils de Lyon (HCL), Centre Mémoire de Ressources et de Recherche [Nice] (CMRR Nice), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice), Laboratoire de génie des procédés - environnement - agroalimentaire (GEPEA), Mines Nantes (Mines Nantes)-Université de Nantes - Faculté des Sciences et des Techniques, Université de Nantes (UN)-Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre National de la Recherche Scientifique (CNRS), CHU Amiens-Picardie, Système Nerveux Autonome - Epidémiologie, Physiologie, Ingénierie, Santé (SNA-EPIS), Université Jean Monnet [Saint-Étienne] (UJM)-Centre Hospitalier Universitaire de Saint-Etienne, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CHU Rouen, Normandie Université (NU), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Toulouse Neuro Imaging Center (ToNIC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Laboratoire de Psychologie et NeuroCognition (LPNC), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Imagerie et cerveau, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), CATI Multicenter Neuroimaging Platform (CATI), 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), 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, Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), 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 et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neuroimagerie Assistée par Ordinateur (LNAO), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université de Bordeaux (UB), Pôle de Santé publique [CHU Bordeaux], CHU de bordeaux, Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Centre National de la Recherche Scientifique (CNRS), Fédération des Centres Mémoire de Ressource et de Recherche du Sud de la France [CHU Toulouse] (F-CMRR-SF), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Mémoire de Ressources et de Recherche [Lille-Bailleul] (CMRR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Roger Salengro [Lille], Centre Mémoire de Ressources et de Recherches [Bordeaux], Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-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)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centre de Mémoire de Ressources et de Recherche [Paris Nord], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Cité (USPC), Maladie d'Alzheimer : marqueurs génétiques et vasculaires, neuropsychologies (EA 4468), Université Paris Descartes - Paris 5 (UPD5)-Groupe hospitalier Broca, Centre de Mémoire de Ressources et de Recherche [Paris Broca], AP-HP - Hôpital Broca [Paris], Centre de Mémoire de Ressources et de Recherche [Hôpital Pellegrin, Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin [Bordeaux], Centre de Mémoire de Ressources et de Recherche [Hôpital Xavier Arnozan, Bordeaux], Hôpital Xavier Arnozan - CHU de Bordeaux, Centres Mémoire de Ressources et de Recherche [Hôpital Gui de Chauliac, Montpellier] (CMRR), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac, Centre de Mémoire de Ressources et de Recherche [Hôpital La Timone, Marseille], Hôpital de la Timone [CHU - APHM] (TIMONE)-CHU Marseille, Centre Mémoire de Ressources et de Recherche [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre Mémoire de Ressources et de Recherche [Lyon] (CMRR), Hospices Civils de Lyon (HCL)-Hôpital des Charpennes [CHU - HCL], Cognition Behaviour Technology (CobTek), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Institut Claude Pompidou [Nice] (ICP - Nice)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Centre Mémoire Ressources et Recherche [Dijon] (CMRR Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Mémoire de Ressources et de Recherche [CHU Amiens], Clinique de la Mémoire [Hôpitaux Universitaires Paris-Seine-Saint-Denis], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Mémoire de Ressources et de Recherche [CHU de Saint-Etienne Hôpital Nord], CHU de Saint-Étienne Hôpital Nord [Saint Etienne], Centre Mémoire de Ressources et de Recherche [CHU de Saint-Etienne Hôpital de la Charité], CHU de Saint-Étienne Hôpital la Charite, Service de neurologie [Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Centre Mémoire de Ressources et de Recherche [CHU de Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Mémoire [CHU de Toulouse], Centre Mémoire de Ressources et de Recherche [CHRU de Poitiers La Miletrie], CHRU de Poitiers La Miletrie [Poitiers], Centre Mémoire de Ressources et de Recherche [CHU Grenoble Alpes-Site NORD, La Tronche], CHU Grenoble Alpes - Site NORD [La Tronche], Centre Mémoire de Ressources et de Recherche [CHRU de Tours Hôpital Bretonneau], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau [Tours], Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Mémoire de Ressources et de Recherche [Hôpitaux Civils de Colmar, Strasbourg], Hôpitaux Civils de Colmar, Centre Mémoire de Ressources et de Recherche [CHU de Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Mémoire de Ressources et de Recherche [CHU Clermont-Ferrand] (CMRR), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Mémoire de Ressources et de Recherche [CHRU de Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Mémoire de Ressources et de Recherche [CHRU de Besançon] (CMRR), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques [CHRU de Besançon], Centre pour l’Acquisition et le Traitement des Images [Saclay] (CATI), 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)-Institut d'imagerie biomédicale (I²BM), Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay, The MEMENTO cohort was sponsored by the Fondation Plan Alzheimer (Alzheimer Plan 2008–2012). This work was also supported by the following : CIC 1401-EC, Bordeaux University Hospital, Inserm and the University of Bordeaux., on behalf of the MEMENTO cohort Study Group, BMC, BMC, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Mémoire de Ressources et de Recherche [CHU de Saint-Etienne] (CMRR 42), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA), Mines Nantes (Mines Nantes)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Laboratoire de Psychologie et NeuroCognition (LPNC ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut d'imagerie biomédicale (I²BM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Toulouse - CHU Toulouse-Hôpital La Grave-Casselardit [Toulouse], Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-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)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Gui de Chauliac-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital des Charpennes [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Institut Claude Pompidou [Nice] (ICP - Nice), Centre Mémoire de Ressources et de Recherche [CHU de Toulouse, Hôpital Purpan], Hôpital Purpan [Toulouse], Hôpital Bretonneau [Tours]-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), INSERM Unit 708-Neuroepidemiology, Paris, France, Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] ( IM2A ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Epidémiologie et anlyses en santé publique: risques, maladies chroniques et handicaps, Université Paul Sabatier - Toulouse 3 ( UPS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Neurologie [Lille], Hôpital Roger Salengro-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Kalray, Service de gériatrie, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Epidémiologie, santé publique et développement, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR99-ISPED, Institut de recherche en biothérapie ( IRB ), Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Université de Montpellier ( UM ), Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Département de Médecine Interne et Gérontologie clinique, CHU Angers, Centre de recherche en neurosciences de Lyon ( CRNL ), 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 ), Laboratoire de génie des procédés - environnement - agroalimentaire ( GEPEA ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Nantes ( UN ) -IMT Atlantique Bretagne-Pays de la Loire ( IMT Atlantique ) -Université Bretagne Loire ( UBL ) -Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique ( ONIRIS ), Laboratoire de Neurosciences Fonctionnelles et Pathologies ( LNFP ), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), AP-HP Hôpital Avicenne [Bobigny], Centre Hospitalier Universitaire de Saint-Etienne ( CHU de Saint-Etienne ), Risque cardiovasculaire, rigidité-fibrose et hypercoagulabilité ( RCV ), Université Henri Poincaré - Nancy 1 ( UHP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagerie cérébrale et handicaps neurologiques, Centre Mémoire de Ressources et de Recherche ( CM2R ), CHU de Poitiers-Hôpital Jean Bernard, Unité de Neuropsychologie, CHU Grenoble, Université de Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Nantes ( UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Hôpital Nord Laënnec, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne ( NPsy-Sydo ), CHU Clermont-Ferrand-Université Clermont Auvergne ( UCA ), Service de Médecine Interne Gériatrique ( BREST - SMIG ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] ( CAPS ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre d'Acquisition et de Traitement des Images [Paris], Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Service NEUROSPIN ( NEUROSPIN ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, 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 ), Laboratoire Jacques-Louis Lions ( LJLL ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Epidemiologie-Biostatistique [Bordeaux], Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Bordeaux Ségalen [Bordeaux 2], Service de médecine nucléaire [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Laboratoire de Neuroimagerie Assistée par Ordinateur ( LNAO ), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Université de Bordeaux (UB), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Institut Claude Pompidou [Nice] (ICP - Nice), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Hôpital Bretonneau [Tours], Centre Mémoire de Ressources et de Recherche [CHU de Clermont-Ferrand], CHU Clermont-Ferrand, Centre Mémoire de Ressources et de Recherche [CHRU de Besançon], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz-Hôpital Saint-Jacques [CHRU de Besançon], Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Service NEUROSPIN (NEUROSPIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut d'imagerie biomédicale (I²BM), Sorbonne Université, Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut d'imagerie biomédicale (I²BM), Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et nanosciences d'Alsace, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Université de Strasbourg (UNISTRA)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Université de Strasbourg (UNISTRA), Groupe hospitalier Pellegrin [Bordeaux] -CHU Bordeaux [Bordeaux], COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Institut Claude Pompidou [Nice] (ICP - Nice)-Université Côte d'Azur (UCA), CHU Lille, CNRS, Inserm, Université de Lille, Troubles cognitifs dégénératifs et vasculaires - U1171, Troubles cognitifs dégénératifs et vasculaires - U 1171 [TCDV], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute ( ICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique ( CNRS ), Fédération des Centres Mémoire de Ressource et de Recherche du Sud de la France [CHU Toulouse] ( F-CMRR-SF ), Troubles cognitifs dégénératifs et vasculaires ( DN2M ), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ) -INSERM, Centre Mémoire de Ressources et de Recherche [Lille-Bailleul] ( CMRR ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ) -Hôpital Roger Salengro [Lille], Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie ( ICube ), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg ( ENGEES ) -Université de Strasbourg ( UNISTRA ) -Institut National des Sciences Appliquées - Strasbourg ( INSA Strasbourg ), Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Centre National de la Recherche Scientifique ( CNRS ) -Matériaux et nanosciences d'Alsace, 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 ) -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 ) -Centre National de la Recherche Scientifique ( CNRS ) -Réseau nanophotonique et optique, Université de Strasbourg ( UNISTRA ) -Université de Haute-Alsace (UHA) Mulhouse - Colmar ( Université de Haute-Alsace (UHA) ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Strasbourg ( UNISTRA ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Sorbonne Paris Cité ( USPC ), Maladie d'Alzheimer : marqueurs génétiques et vasculaires, neuropsychologie ( EA 4468 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Groupe hospitalier Broca, Centre Hospitalier Universitaire de Bordeaux-Groupe hospitalier Pellegrin [Bordeaux], Centres Mémoire de Ressources et de Recherche [Hôpital Gui de Chauliac, Montpellier] ( CMRR ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Gui de Chauliac, Hôpital de la Timone [CHU - APHM] ( TIMONE ) -CHU Marseille, Centre Mémoire de Ressources et de Recherche [Lyon] ( CMRR ), Hospices Civils de Lyon ( HCL ) -Hôpital des Charpennes [CHU - HCL], Hospices Civils de Lyon ( HCL ), Cognition Behaviour Technology ( CobTek ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -CHU Nice-Institut Claude Pompidou [Nice] ( ICP - Nice ), Centre Mémoire de Ressources et de Recherche [Nice] ( CMRR Nice ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -CHU Nice, Centre Mémoire Ressources et Recherche [Dijon] ( CMRR Dijon ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), CHU Amiens Picardie - Site Nord (Hôpital Nord) [Amiens], CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Centre Hospitalier Régional Universitaire de Tours ( CHRU TOURS ) -Hôpital Bretonneau [Tours], Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean-Minjoz [CHRU de Besançon]-Hôpital Saint-Jacques [CHRU de Besançon], Centre pour l’Acquisition et le Traitement des Images [Saclay] ( CATI ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -NeuroSpin-Institut d'imagerie biomédicale (I²BM), Sorbonne Universités, Département de Médecine Nucléaire [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [APHP], Laboratoire d'Imagerie Biomédicale ( LIB ), and Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC )
Subjects: Male, [SDV]Life Sciences [q-bio], Neuroimaging, Neuropsychological Tests, Spinal Puncture, Pattern Recognition, Automated, [ SDV.NEU.PC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Diagnostic Self Evaluation, [ SDV.NEU.SC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Cognitive aging, Fluorodeoxyglucose F18, Image Processing, Computer-Assisted, Humans, Cognitive Dysfunction, Longitudinal Studies, ComputingMilieux_MISCELLANEOUS, Aged, [ SDV ] Life Sciences [q-bio], Cohort studies, Natural history studies (prognosis), Alzheimer''s disease, Research, Brain, Organ Size, Magnetic Resonance Imaging, [SDV] Life Sciences [q-bio], Research Design, Positron-Emission Tomography, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [ SCCO.NEUR ] Cognitive science/Neuroscience, Female, France, Radiopharmaceuticals, Alzheimer’s disease, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract: Background The natural history and disease mechanisms of Alzheimer’s disease and related disorders (ADRD) are still poorly understood. Very few resources are available to scrutinise patients as early as needed and to use integrative approaches combining standardised, repeated clinical investigations and cutting-edge biomarker measurements. Methods In the nationwide French MEMENTO cohort study, participants were recruited in memory clinics and screened for either isolated subjective cognitive complaints (SCCs) or mild cognitive impairment (MCI; defined as test performance 1.5 SD below age, sex and education-level norms) while not demented (Clinical Dementia Rating [CDR]
Published: 2017

23. NAITRE study on the impact of conditional cash transfer on poor pregnancy outcomes in underprivileged women: protocol for a nationwide pragmatic cluster-randomised superiority clinical trial in France

Author: Elise Thellier, Frédérique Falchier, Philippe Deruelle, Mathieu Morin, Catherine Deneux-Tharaux, Isabelle Fournel, Muriel Doret, Ghada Hatem, Isabelle Le Ray, Franck Perrotin, Laurent Laforet, Nicolas Meunier-Beillard, Thiphaine Barjat, Bruno Crépon, Esther Duflo, Thomas Schmitz, Anne-Claire Bertaux, Xavier Carcopino-Tusoli, Marc Bardou, Astrid Eckman-Lacroix, Aurélie Godard-Marceaux, Centre d'Investigation Clinique 1432 (Dijon) - Module Plurithématique : Périnatalité Cancérologie Handicap et Ophtalmologie (CIC-P803), Université de Bourgogne (UB)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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, Centre de Recherche en Économie et Statistique (CREST), Ecole Nationale de la Statistique et de l'Analyse de l'Information [Bruz] (ENSAI)-École polytechnique (X)-École Nationale de la Statistique et de l'Administration Économique (ENSAE Paris)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Service de Gynécologie Obstétrique [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Gynécologie Obstétrique [AP-HP Hôpital Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de Gynécologie-Obstétrique (BREST - Gynéco-Obs), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Gynécologie - Obstétrique [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Service de Gynécologie et Obstétrique [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'Obstétrique-Gynécologie [Marseille], Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille- Hôpital Nord [CHU - APHM], Département d'obstétrique et de gynécologie [AP-HP Hôpital Robert Debré], 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), Service de Gynécologie Obstétrique (Gynéco-Obs - SAINT ETIENNE), Hôpital Nord (Saint Etienne), Service de gynécologie-obstétrique [CHU Toulouse], CHU Toulouse [Toulouse], Service de gynécologie-obstétrique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de gynécologie obstétrique [CH Saint Denis], Centre Hospitalier de Saint-Denis [Ile-de-France], Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), DHU Risques Et Grossesse, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Department of Economics (Massachusetts Institute of Technology, Cambridge, Massachusetts), Massachusetts Institute of Technology (MIT), Service de gynécologie–obstétrique, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Ecole Nationale de la Statistique et de l'Analyse de l'Information [Bruz] (ENSAI)-École polytechnique (X)-École Nationale de la Statistique et de l'Administration Économique (ENSAE ParisTech )-Centre National de la Recherche Scientifique (CNRS), Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre d'Investigation Clinique de Besançon (CICB), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang Bourgogne Franche-Comté-Université de Franche-Comté (UFC), Service de gynécologie-obstétrique [CHRU Besançon], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Université Paris Diderot - Paris 7 (UPD7)-AP-HP Hôpital universitaire Robert-Debré [Paris], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (UR 481) (NEURO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Département d'obstétrique et de gynécologie [Hôpital Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Gynécologie-Obstétrique [CHRU Tours], Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Massachusetts Institute of Technology. Department of Economics, Duflo, Esther, Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction Générale de l'Organisation des Soins (DGOS)-Université de Bourgogne (UB), Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique 1432 (Dijon) - Module Plurithématique : Périnatalité Cancérologie Handicap et Ophtalmologie ( CIC-P803 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Direction Générale de l'Organisation des Soins (DGOS)-Université de Bourgogne ( UB ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche en Économie et Statistique ( CREST ), Ecole Nationale de la Statistique et de l'Analyse de l'Information [Bruz] ( ENSAI ) -École polytechnique ( X ) -École Nationale de la Statistique et de l'Administration Économique ( ENSAE ParisTech ), Laboratoire de Neurosciences Intégratives et Cliniques - UFC ( NEURO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Centre d'Investigation Clinique de Besançon ( CICB ), Etablissement Français du Sang Bourgogne Franche-Comté-Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Franche-Comté ( UFC ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Service de Gynécologie-Obstétrique ( BREST - Gynéco-Obs ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Hôpital Femme Mère Enfant [CHU - HCL] ( HFME ), Hospices Civils de Lyon ( HCL ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Assistance Publique - Hôpitaux de Marseille ( APHM ) -CHU Marseille- Hôpital Nord [CHU - APHM], Université Paris Diderot - Paris 7 ( UPD7 ) -AP-HP Hôpital universitaire Robert-Debré [Paris], Service de Gynécologie Obstétrique ( Gynéco-Obs - SAINT ETIENNE ), Centre Hospitalier Universitaire de Toulouse - CHU Toulouse (FRANCE), CHRU Tours, CH Saint-Denis, Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique ( CRESS - U1153 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Assistance publique - Hôpitaux de Paris (AP-HP), 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 ), and Massachusetts Institute of Technology
Subjects: Research design, Adult, Pediatrics, medicine.medical_specialty, Maternal Health, Gestational Age, Prenatal care, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Vulnerable Populations, organisation of health services, clinical governance, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Fetus, Pregnancy, Obstetrics and Gynaecology, Clinical endpoint, Protocol, Medicine, Humans, Infant Health, 030212 general & internal medicine, Socioeconomic status, [ SDV.MHEP.GEO ] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Referral and Consultation, Motivation, maternal medicine, 030219 obstetrics & reproductive medicine, business.industry, Conditional cash transfer, Infant, Newborn, Pregnancy Outcome, Gestational age, Prenatal Care, General Medicine, Patient Acceptance of Health Care, medicine.disease, 3. Good health, Clinical trial, Pregnancy Complications, Social Class, Research Design, Family medicine, Female, France, business
Abstract: IntroductionPrenatal care is recommended during pregnancy to improve neonatal and maternal outcomes. Women of lower socioeconomic status (SES) are less compliant to recommended prenatal care and suffer a higher risk of adverse perinatal outcomes. Several attempts to encourage optimal pregnancy follow-up have shown controversial results, particularly in high-income countries. Few studies have assessed financial incentives to encourage prenatal care, and none reported materno-fetal events as the primary outcome. Our study aims to determine whether financial incentives could improve pregnancy outcomes in women with low SES in a high-income country.Methods and analysisThis pragmatic cluster-randomised clinical trial includes pregnant women with the following criteria: (1) age above 18 years, (2) first pregnancy visit before 26 weeks of gestation and (3) belonging to a socioeconomically disadvantaged group. The intervention consists in offering financial incentives conditional on attending scheduled pregnancy follow-up consultations. Clusters are 2-month periods with random turnover across centres. A composite outcome of maternal and neonatal morbidity and mortality is the primary endpoint. Secondary endpoints include maternal or neonatal outcomes assessed separately, qualitative assessment of the perception of the intervention and cost-effectiveness analysis for which children will be followed to the end of their first year through the French health insurance database. The study started in June 2016, and based on an expected decrease in the primary endpoint from 18% to 14% in the intervention group, we plan to include 2000 women in each group.Ethics and disseminationEthics approval was first gained on 28 September 2014. An independent data security and monitoring committee has been established. Results of the main trial and each of the secondary analyses will be submitted for publication in a peer-reviewed journal.Trial registration numberNCT02402855; pre-results.
Published: 2017

24. Recommandations sur la gestion du risque et la prise en charge urologique du patient adulte atteint de dysraphisme spinal (spina bifida)

Author: Manunta, Andréa, Peyronnet, Benoît, Olivari-Philiponnet, Camille, Chartier-Kastler, Emmanuel J., Saussine, Christian C., Phé, Véronique, Robain, Gilberte, Denys, Pierre, Even, Alexia, Samson, Emmanuelle, Grise, Phillippe, Karsenty, G., Hascoet, Juliette, Castel-Lacanal, Evelyne, Charvier, Kathleen F., Guinet-Lacoste, Amandine, Chesnel, Camille, Amarenco, Gérard, Haffner, F., Haddad, Mirna, Le Normand, Loïc, Perrouin-Verbe, Marie Aimée, Perrouin-Verbe, Brigitte, de Seze, Marianne, Ruffion, Alain, Gamé, Xavier, CHU Pontchaillou [Rennes], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Hôpital Raymond Poincaré [Garches], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Strasbourg, CHU Tenon [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), CHU Rouen, Normandie Université (NU), Chirurgie urologique et transplantation rénale [Hôpital de la Conception - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service Médecine physique et de réadaptation [CHU Toulouse], Pôle Neurosciences [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Médecine Physique et Réadaptation [Hôpital Henry Gabrielle - Lyon], Hôpital Henry Gabrielle [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Groupe de RecherchE CliniquE en Neuro-urologie [CHU Tenon] (GRC 1 - GREEN ), CHU Marseille, Centre hospitalier universitaire de Nantes (CHU Nantes), Clinique Saint Augustin, and Hospices Civils de Lyon (HCL)
Subjects: Quality of life, Complications, [SDV]Life Sciences [q-bio], Urology, Urinary incontinence, Neurogenic, Spinal dysraphism, Spina bifida, Urinary bladder
Abstract: International audience; Introduction: Improved life expectancy and prenatal screening have changed the demographics of spina bifida (spinal dysraphism) which has presently become a disease of adulthood. Urinary disorders affect almost all patients with spinal dysraphism and are still the leading cause of mortality in these patients. The aim of this work was to establish recommendations for urological management that take into account the specificities of the spina bifida population. Materials and methods: National Diagnosis and Management Guidelines (PNDS) were drafted within the framework of the French Rare Diseases Plan at the initiative of the Centre de Référence Maladies Rares Spina Bifida - Dysraphismes of Rennes University Hospital. It is a collaborative work involving experts from different specialties, mainly urologists and rehabilitation physicians. We conducted a systematic search of the literature in French and English in the various fields covered by these recommendations in the MEDLINE database. In accordance with the methodology recommended by the authorities (Guide_methodologique_pnds.pdf, 2006), proposed recommendations were drafted on the basis of this literature review and then submitted to a review group until a consensus was reached. Results: Bladder dysfunctions induced by spinal dysraphism are multiple and varied and evolve over time. Management must be individually adapted and take into account all the patient's problems, and is therefore necessarily multi-disciplinary. Self-catheterisation is the appropriate micturition method for more than half of the patients and must sometimes be combined with treatments aimed at suppressing any neurogenic detrusor overactivity (NDO) or compliance alteration (anticholinergics, intra-detrusor botulinum toxin). Resort to surgery is sometimes necessary either after failure of non-invasive treatments (e.g. bladder augmentation in case of NDO resistant to pharmacological treatment), or as a first line treatment in the absence of other non-invasive alternatives (e.g. aponeurotic suburethral tape or artificial urinary sphincter for sphincter insufficiency; urinary diversion by ileal conduit if self-catheterisation is impossible). Conclusion: Spinal dysraphism is a complex pathology with multiple neurological, orthopedic, gastrointestinal and urological involvement. The management of bladder and bowel dysfunctions must continue throughout the life of these patients and must be integrated into a multidisciplinary context.
Published: 2023

25. Association Between Multidrug-Resistant Bacteria and Mortality in Critically Ill Patients

Author: Gary Duclos, Ines Lakbar, Mohamed Boucekine, Georges Lolo, Nadim Cassir, Marc Leone, Department of Anesthesiology and Intensive Care Unit, Nord Hospital, Assistance Publique Hôpitaux Universitaire de Marseille, CHU Marseille, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), 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 - 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), Department of Anesthesiology and Intensive Care Unit, Nord Hospital, Assistance Publique Hôpitaux Universitaire de Marseille, Aix Marseille University, Marseille, Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service Anesthésie et Réanimation [Hôpital Nord - APHM], and Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM]
Subjects: [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Pharmacology (medical), General Medicine, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract: International audience
Published: 2023

26. Comparative outcomes of extracorporeal membrane oxygenation for COVID-19 delivered in experienced European centres during successive SARS-CoV-2 variant outbreaks (ECMO-SURGES): an international, multicentre, retrospective cohort study

Author: Matthieu Schmidt, David Hajage, Micha Landoll, Benjamin Pequignot, Elise Langouet, Matthieu Amalric, Armand Mekontso-Dessap, Luis Chiscano-Camon, Katy Surman, Dylan Finnerty, Patricia Santa-Teresa, Antonio Arcadipane, Pablo Millán, Roberto Roncon-Albuquerque, Aaron Blandino-Ortiz, Pablo Blanco-Schweizer, Pilar Ricart, Ricardo Gimeno-Costa, Carlos Luis Albacete, Philip Fortuna, Peter Schellongowski, Dieter Dauwe, Hadrien Winiszewski, Antoine Kimmoun, Bruno Levy, Greet Hermans, Giacomo Grasselli, Guillaume Lebreton, Christophe Guervilly, Gennaro Martucci, Christian Karagiannidis, Jordi Riera, Alain Combes, 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), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), 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), Pharmacoépidémiologie et évaluation des soins [iPLesp] (PEPITES), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université (SU), Universität Witten Herdecke, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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), CHU Marseille, IMRB - 'Biomechanics and Respiratory Apparatus' [Créteil] (U955 Inserm - UPEC), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-CHU Henri Mondor [Créteil], Vall d'Hebron University Hospital [Barcelona], Royal Papworth Hospital [Cambridge, UK] (RPH), Hospital General Universitario 'Gregorio Marañón' [Madrid], Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), Universidad Loyola Andalucía = Loyola University Andalucía, Hospital de São João [Porto], Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Rio Hortega University Hospital (Hospital Universitario Río Hortega) [Valladolid, Spain] (RHUH), Germans Trias i Pujol University Hospital [Badalona, Barcelona, Spain] (GTPUH), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Hospital Clínico Universitario Virgen de la Arrixaca = University Hospital Virgen de la Arrixaca [Murcia], Centro Hospitalar de Lisboa Central E.P.E, Medizinische Universität Wien = Medical University of Vienna, University Hospitals Leuven [Leuven], Service d'anesthésie et soins intensifs [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), and Vall d’Hebron Research Institute (VHIR)
Subjects: Pulmonary and Respiratory Medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Abstract: International audience
Published: 2023

27. Clinical features, therapeutic choice and response by phototype in psoriasis: analysis of the French PsoBioTeq cohort

Author: Salle-Siri, Romain, Tubach, Florence, Arlegui, Hugo, Curmin, Raphaëlle, Viguier, Manuelle, Beylot-Barry, Marie, Dupuy, Alain, Bénéton, Nathalie, Joly, Pascal, de Rycke, Yann, Jullien, Denis, Mahé, Emmanuel, Paul, Carle, Richard, Marie‐aleth, Bachelez, Hervé, Zago, Marilyn, Chosidow, Olivier, Sbidian, Emilie, Hôpital Henri Mondor, 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)-Sorbonne Université (SU), Hôpital Robert Debré, BoRdeaux Institute in onCology (Inserm U1312 - BRIC), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre Hospitalier Le Mans (CH Le Mans), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Centre Hospitalier Victor Dupouy, 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, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Dynamic Microbiology - EA 7380 (DYNAMIC), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est (UPE)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CIC - CHU Henri Mondor, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience; BACKGROUND: Little is known about phototype and the response to systemic treatment in psoriasis. OBJECTIVE: To assess the characteristics of psoriasis, the therapeutic choice and its efficacy according to phototype. METHODS: We included patients from the PsoBioTeq cohort initiating a first biologic. Patients were classified according to their phototype. The evaluation included disease characteristics, choice of the initial biologic and therapeutic response at 12 months based on PASI 90 and DLQI 0/1. RESULTS: Of the 1400 patients included, 423 (30.2%), 904 (64.6%) and 73 (5.2%) were in the phototype I-II, III-IV and V-VI groups, respectively. The V-VI group had a higher initial DLQI, more frequently initiated ustekinumab. Patients in the phototype V-VI group maintained the first sequence of biologic as the other phototype groups, even though the proportion of patients reaching the PASI 90 and DLQI 0/1 at 12 months was lower in this group than other groups. CONCLUSION: Patient phototype seems associated with quality of life and choice of the initial biologic in psoriasis. Phototype V-VI group less frequently switched treatments than did the other groups when the response was not efficient.
Published: 2023

28. Serotonin transporter gene expression predicts the worsening of suicidal ideation and suicide attempts along a long-term follow-up of a Major Depressive Episode

Author: Jorge Lopez-Castroman, Thomas Desmidt, Karine Baumstarck, Pascale Mazzola-Pomietto, Emilie Olié, Philippe Courtet, Julia-Lou Consoloni, Marie-Noëlle Lefebvre, Pierre-Michel Llorca, Mocrane Abbar, El Chérif Ibrahim, Raoul Belzeaux, Jean Naudin, Jean-Michel Azorin, Wissam El-Hage, Xavier Zendjidjian, Emmanuel Haffen, Ludovic Samalin, Fondation FondaMental [Créteil], Neurobiologie des interactions cellulaires et neurophysiopathologie - NICN ( NICN ), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique ( CNRS ), CIC-CPCET, Hôpital de la Timone [CHU - APHM] ( TIMONE ), Assistance Publique - Hôpitaux de Marseille ( APHM ), Neuropsychiatrie : recherche épidémiologique et clinique, Université Montpellier 1 ( UM1 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Institut de Neurosciences de la Timone ( INT ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Imagerie et cerveau, Université de Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne ( NPsy-Sydo ), CHU Clermont-Ferrand-Université Clermont Auvergne ( UCA ), Service de psychiatrie adulte, Université de Nîmes ( UNIMES ) -Centre Hospitalier Régional Universitaire de Nîmes ( CHRU Nîmes ) -Hôpital Universitaire Carémeau [Nîmes], Centre Hospitalier Régional Universitaire de Nîmes (.), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] ( CAPS ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Aix Marseille Université ( AMU ), Pôle de psychiatrie, Assistance Publique - Hôpitaux de Marseille ( APHM ) -Hôpital Sainte-Marguerite [CHU - APHM] ( Hôpitaux Sud ) -CHU Marseille, Clinique Psychiatrique Universitaire [Tours], CHRU Tours, Pathologies du système nerveux : recherche épidémiologique et clinique, Université Montpellier 1 ( UM1 ) -IFR76-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Pôle de Psychiatrie Universitaire Solaris, Marseille, Hôpital Sainte-Marguerite [CHU - APHM] ( Hôpitaux Sud ), Neurobiologie des interactions cellulaires et neurophysiopathologie - NICN (NICN), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Assistance Publique - Hôpitaux de Marseille (APHM), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aix Marseille Université (AMU), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-CHU Marseille, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Département Universitaire de Psychiatrie - [Hôpital Sainte Marguerite - APHM] (Hôpitaux Sud), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Centre National de la Recherche Scientifique (CNRS)-Université de la Méditerranée - Aix-Marseille 2, Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Oncology, Male, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Gene Expression, Suicide, Attempted, [ SDV.NEU.SC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 0302 clinical medicine, Surveys and Questionnaires, Gene expression, Pharmacology (medical), Longitudinal Studies, Prospective cohort study, Major depressive episode, Suicidal ideation, Serotonin transporter, ComputingMilieux_MISCELLANEOUS, Serotonin Plasma Membrane Transport Proteins, biology, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Middle Aged, 16. Peace & justice, 3. Good health, Psychiatry and Mental health, Neurology, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [ SCCO.NEUR ] Cognitive science/Neuroscience, Biomarker (medicine), Female, France, medicine.symptom, Adult, medicine.medical_specialty, Peripheral blood mononuclear cell, Polymorphism, Single Nucleotide, Suicidal Ideation, [ SDV.NEU.PC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, 03 medical and health sciences, Internal medicine, medicine, Humans, Genetic Testing, RNA, Messenger, Biological Psychiatry, Pharmacology, Depressive Disorder, Major, Suicide attempt, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, 030227 psychiatry, ROC Curve, Case-Control Studies, biology.protein, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: The quest for biomarkers in suicidal behaviors has been elusive so far, despite their potential utility in clinical practice. One of the most robust biological findings in suicidal behaviors is the alteration of the serotonin transporter function in suicidal individuals. Our main objective was to investigate the predictive value of the serotonin transporter gene expression (SLC6A4) for suicidal ideation and as secondary, for suicide attempts in individuals with a major depressive episode (MDE). A 30-week prospective study was conducted on 148 patients with a MDE and 100 healthy controls including 4 evaluation times (0, 2, 8 and 30 weeks). Blood samples and clinical data were collected and SLC6A4 mRNA levels were measured from peripheral blood mononuclear cells using RT-qPCR. We first demonstrated the stability and reproducibility of SLC6A4 mRNA expression measures over time in healthy controls (F=0.658; p=0.579; η2=0.008; ICC=0.91, 95% CI [0.87-0.94]). Baseline SLC6A4 expression level (OR=0.563 [0.340-0.932], p=0.026) as well as early changes in SLC6A4 expression between baseline and the 2nd week (β=0.200, p=0.042) predicted the worsening of suicidal ideation (WSI) in the following 8 weeks. Moreover, changes in SLC6A4 expression between the 2nd and 8th weeks predicted the occurrence of a suicide attempt within 30 weeks (OR=10.976 [1.438-83.768], p=0.021). Altogether, the baseline level and the changes in SLC6A4 mRNA expression during a MDE might predict the WSI and the occurrence of suicidal attempts and could be a useful biomarker in clinical practice.
Published: 2017

29. Antenatal prognostic factor of fetal echogenic bowel

Author: Fabien Stenard, Pascal de Lagausie, Florence Bretelle, Nicole Philip, Pascale Hoffmann, Anderson Loundou, Pierre Mace, Isabelle Mortier, Jonathan Lopater, Marie Christine Pellissier, Sabine Sigaudy, Claude D'Ercole, M. Capelle, Thierry Merrot, Candice Ronin, Annie Levy, Service de Génétique, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Gynépole, Aix Marseille Université (AMU)- Hôpital Nord [CHU - APHM], Babolat VS, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité d'Aide Méthodologique, Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Obstétrique-Gynécologie [Marseille], Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille- Hôpital Nord [CHU - APHM], Biologie du Cancer et de l'Infection (BCI ), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), 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)-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d’Aide à la Procréation, Département de Génétique et Procréation (CECOS), Hôpital Couple Enfant de Grenoble-CHU de Grenoble, Department of Obstetrics and Gynaecology, University Hospital of Grenoble, La Tronche, France, UMR 6578 : Anthropologie Bio-Culturelle (UAABC), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Service de Chirurgie et Radiologie Pédiatrique, Université de la Méditerranée - Aix-Marseille 2, Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Adult, Pediatrics, medicine.medical_specialty, Intrauterine growth restriction, Gestational Age, Ultrasonography, Prenatal, 03 medical and health sciences, 0302 clinical medicine, Meconium, Pregnancy, Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Echogenic Bowel, Humans, 030212 general & internal medicine, Retrospective Studies, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, business.industry, Infant, Newborn, Pregnancy Outcome, Obstetrics and Gynecology, Gestational age, Retrospective cohort study, medicine.disease, 3. Good health, Reproductive Medicine, Amniocentesis, Female, Trisomy, business
Abstract: International audience; Objective: The aim of this study was to identify antenatal prognostic factors of neonatal outcomes in cases of fetal echogenic bowel (FEB). Study design: A retrospective study in three tertiary referral centers including fetal echogenic bowel over a 10-year period (from January 2003 to December 2013). The echogenicity of the fetal bowel was graded from 1 to 3, according to Slotnick's definition. Associated echographic findings such as bowel dilations, gallbladder abnormalities, calcifications, extra-abdominal abnormalities, intrauterine growth restriction (IUGR) and a decrease in amniotic fluid volume, if present were also recorded. This was followed by the FEB's sonographic evolution. The sonographic evolution was considered favorable if it was stable or decreasing and unfavorable if the echogenicity of the bowel increased or if additional sonographic findings appeared. Neonates had a pediatric examination in the delivery room and upon discharge from the maternity hospital. An outcome was considered good in the case of on-term delivery of a newborn with normal clinical examination and meconium elimination. Results: Complete pregnancy outcome data were available for 409 pregnancies. 338 newborns had uneventful outcomes (82.6%). Antenatal exploration diagnosed 4 cases of aneuploidy (1 case of trisomy 13, 1 case of trisomy 18 and 2 cases of triploidies), 16 cases of congenital infections, 9 cases of cystic fibrosis and 11 cases of bowel abnormalities. After a multivariate analysis, we discovered the sonographic grade of the echogenic bowel was not a prognostic factor of neonatal outcome. The isolated fetal echogenic bowel had a 6.6-fold increase chance of uneventful outcomes (adjusted odd ratio (aOR) 6.6, 95% CI 3-14.4). Notably, favorable sonographic evolution (aOR 8.1, 95% CI 4.1-16) and late gestational age at the time of the diagnosis (aOR 1.17, 95% CI 1.07-1.27) are independent, good prognostic factors of good neonatal outcomes. None of the 180 fetuses with isolated fetal echogenic bowel and favorable sonographic evolution had adverse outcomes. Among these, 4 cases (0.98%) of aneuploidy, 17 cases (4.2%) of congenital infections and 9 cases (2.2%) of cystic fibroses were also diagnosed. No cases of Down syndrome (DS) were reported. Conclusion: Our study shows that the grade should not be considered a prognostic factor of neonatal outcomes. Our data suggests the need to reevaluate the concept of systematic amniocentesis. Sonographic evolution of fetal bowel is an independent, strong prognostic factor for good neonatal outcomes. It also better defines the FEB prognostic. (C) 2017 Elsevier B.V. All rights reserved.
Published: 2017

30. Guideline choice for CTG analysis influences first caesarean decision

Author: Nadège Vejux, Florence Bretelle, Claude D'Ercole, L. Piechon, Anderson Loundou, Renaud Ledu, Service d'Obstétrique-Gynécologie [Marseille], Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille- Hôpital Nord [CHU - APHM], Unité d'Aide Méthodologique, Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Gynépole, Aix Marseille Université (AMU)- Hôpital Nord [CHU - APHM], and Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, medicine.medical_specialty, Cardiotocography, medicine.medical_treatment, Clinical Decision-Making, Decision Making, Gestational Age, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Medicine, Caesarean section, Oximetry, 030212 general & internal medicine, Fetal Monitoring, 10. No inequality, Retrospective Studies, Gynecology, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, Cesarean Section, business.industry, Obstetrics, Reproducibility of Results, Obstetrics and Gynecology, Guideline, Heart Rate, Fetal, Hydrogen-Ion Concentration, Practice Guidelines as Topic, Pediatrics, Perinatology and Child Health, Female, France, business, Intrapartum Cardiotocography
Abstract: International audience; Objective: To compare intrapartum cardiotocography (CTG) analysis in case of first caesarean section (CS) for non-reassuring CTG according to international guidelines.Methods: Four ObGyns retrospectively analysed first CS for non-reassuring CTG during labour blind to neonatal outcome. CTG were analysed according to French National College of Obstetricians and Gynaecologists (CNGOF) and to the FIGO guidelines. First, CTG analysis was done without obstetrical context, then secondly, it was given. ObGyns stated if CS was justified or not. Inter-operator ObGyn agreement was analysed.Results: Among 587 CS, 100 women met the inclusion criteria with a first CS for non-reassuring CTG. The overall inter observer agreement was low but fair. ObGyns were significantly more concordant using the FIGO than the CNGOF guidelines (kappa coefficient=0.331 [0.27-0.39] versus 0.209 [0.16-0.26] p
Published: 2017

31. Clinical Features, Management, and Outcomes of Immune Checkpoint Inhibitor-Related Cardiotoxicity

Author: Ugo Scemama, Jean-Jacques Grob, Jennifer Cautela, Marc Laine, Michael Peyrol, Alexis Jacquier, Marion Escudier, Franck Paganelli, Fabrice Barlesi, Johan Pinto, Jeremie Barraud, Ariel Cohen, Franck Thuny, N. Malissen, Laurent Bonello, Yann Ancedy, Nathalie Lalevée, Stéphane Ederhy, Sandrine Monestier, Morgane Orabona, Aix Marseille Université (AMU), Hôpital Nord [CHU - APHM], Département de dermatologie [CHU de Montpellier], Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Thrombose, atherothrombose et pharmacologie appliquée, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital de la Timone [CHU - APHM] (TIMONE), Département de dermatologie, CHU Marseille, CHU Marseille, 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), Technologies avancées pour le génôme et la clinique (TAGC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie de l'Endothelium, Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Service de Cardiologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Oncologie multidisciplinaire et innovations thérapeutiques [Hôpital Nord - APHM], Aix Marseille Université (AMU)- Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM]
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, Databases, Factual, Heart Diseases, Cardiology, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030204 cardiovascular system & hematology, Risk Assessment, Young Adult, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Risk Factors, Informed consent, Allergy and Immunology, Neoplasms, Physiology (medical), medicine, Humans, Intensive care medicine, Adverse effect, Aged, Retrospective Studies, Aged, 80 and over, Cardiotoxicity, business.industry, Medical record, Incidence (epidemiology), Cancer, Middle Aged, Institutional review board, medicine.disease, 3. Good health, Clinical trial, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, Cardiology and Cardiovascular Medicine, business
Abstract: Immune checkpoint inhibitors (ICIs) represent a major advance in the treatment of cancer. Although clinical trials reported a low incidence of immune-related cardiovascular adverse events,1 the number of published life-threatening cases of cardiotoxicity is increasing.2 In this descriptive observational analysis, we aimed to describe the clinical manifestations, management, and outcomes of patients who developed ICI-related cardiotoxicity. The medical records of patients with a clinical suspicion of ICI-related cardiotoxicity were reviewed from the databases of 2 cardio-oncology units between March 2015 and April 2017. The patients are managed according to similar protocols. Because no specific follow-up had previously been established for patients receiving ICIs during the study period, the oncologists referred patients receiving ICIs only on the basis of their clinical suspicion of cardiovascular events. These patients had a standardized evaluation including clinical consultation, ECG, transthoracic echocardiography, and measurement of brain natriuretic peptide and troponin I serum levels. The management of cardiotoxicity was left to the physician’s discretion. The study was approved by our institutional review board, and informed consent has been obtained from the subjects. To create a pooled analysis, we also searched PubMed for English articles reporting cases of ICI-related cardiotoxicity until April 2017. We selected …
Published: 2017

32. Prevalence and characteristics of gonadoblastoma in a retrospective multi-center study with follow-up investigations of 70 patients with Turner syndrome and a 45,X/46,XY karyotype

Author: Daphné Karila, Bruno Donadille, Juliane Léger, Claire Bouvattier, Anne Bachelot, Veronique Kerlan, Sophie Catteau-Jonard, Sylvie Salenave, Frédérique Albarel, Claire Briet, Regis Coutant, Aude Brac De La Perriere, Alexander Valent, Jean-Pierre Siffroi, Sophie Christin-Maitre, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Service d'endocrinologie diabétologie pédiatrique [CHU Debré], 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), National Reference Network DSD DevGen, Service d'endocrinologie pédiatrique [CHU Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Lille, Université de Lille, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Endocrinologie, diabète, maladies métaboliques (CHU Marseille, AP-HM), Assistance Publique - Hôpitaux de Marseille (APHM), Centre de référence des maladies rares de l'hypophyse (HYPO), Service d'Endocrinologie, Diabète et Maladies Métaboliques, Endocrinologie pédiatrique[CHU Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Maladies génétiques d'expression pédiatrique (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), CHU Trousseau [APHP], Centre de référence des Maladies Endocriniennes Rares de la Croissance [CHU Saint-Antoine AP-HP] (CRMERC), Service d'Endocrinologie, diabétologie et endocrinologie de la reproduction [CHU Saint-Antoine], Centre de référence des maladies endocriniennes rares de la croissance et du développement [CHU Pitié-Salpêtrière], Service d'Endocrinologie et Médecine de la Reproduction [CHU Pitié-Salpêtrière], Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), UF de Génétique chromosomique [CHU Trousseau], and Couvet, Sandrine
Subjects: Adult, Ovarian Neoplasms, Adolescent, Mosaicism, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Karyotype, Turner Syndrome, General Medicine, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, [SDV] Life Sciences [q-bio], Young Adult, Endocrinology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Prevalence, Humans, Female, Gonadoblastoma, Child, Follow-Up Studies
Abstract: Introduction A gonadectomy is currently recommended in patients with Turner syndrome (TS) and a 45,X/46,XY karyotype, due to a potential risk of gonadoblastoma (GB). However, the quality of evidence behind this recommendation is low. Objective This study aimed to evaluate the prevalence of GB, its characteristics, as well as its risk factors, according to the type of Y chromosomal material in the karyotype. Methods Our study within French rare disease centers included patients with TS and a 45,X/46,XY karyotype, without ambiguity of external genitalia. Clinical characteristics of the patients, their age at gonadectomy, and gonadal histology were recorded. The regions of the Y chromosome, the presence of TSPY regions, and the percentage of 45,X/46,XY mosaicism were evaluated. Results A total of 70 patients were recruited, with a median age of 29.5 years (21.0–36.0) at the end of follow-up. Fifty-eight patients had a gonadectomy, at a mean age of 15 ± 8 years. GB was present in nine cases. Two were malignant, which were discovered at the age of 14 and 32 years, without metastases. Neither the percentage of XY cells within the 45,X/46,XY mosaicism nor the number of TSPY copies was statistically different in patients with or without GB (P = 0.37). However, the entire Y chromosome was frequent in patients with GB (6/9). Conclusions In our study, including a large number of patients with 45,X/46,XY TS, the prevalence of gonadoblastoma is 12.8%. An entire Y chromosome appears as the main risk factor of GB and should favor early gonadectomy. Significant statement About 10% of patients with TS have a karyotype containing Y chromosomal material: 45,X/46,XY. Its presence is related to the risk of GB. Therefore, a prophylactic gonadectomy is currently recommended in such patients. However, the quality of evidence is low. Our objective was to evaluate the prevalence of GB according to the type of Y-chromosomal material. We found a prevalence of GB of 12.8% in a cohort of 70 TS patients. No sign of hyperandrogenism was observed. The entire Y chromosome was the most frequent type of Y-material in patients with GB. As the prognosis of these tumors was good, a delay of surgery might be discussed.
Published: 2022

33. Adverse drug reaction related to drug shortage: A retrospective study on the French National Pharmacovigilance Database

Author: Bourneau-Martin, Delphine, Babin, Marina, Grandvuillemin, Aurelie, Mullet, Charlotte, Salvo, Francesco, Singier, Allison, Cellier, Morgane, Fresse, Audrey, de Canecaude, Claire, Pietri, Tessa, Drablier, Guillaume, Geniaux, Helene, Lagarce, Laurence, Laroche, Marie-Laure, Briet, Marie, Admin, Oskar, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Régional de Pharmacovigilance, de Renseignement sur le Médicament et de Pharmaco épidémiologie de Bourgogne [Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Dijon, 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 Lorraine (CRPV Lorraine), CRHU Nancy, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service Pharmacologie Clinique [CHU Toulouse], Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-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, Centre régional de pharmacovigilance, de pharmaco-épidémiologie et d'information sur les médicaments [Limoges], CHU Limoges, Vieillissement Fragilité Prévention e-Santé (VieSanté), OmégaHealth (ΩHealth), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Laboratoire de Biologie Neurovasculaire Intégrée [Angers] (CNRS UMR6214 - INSERM U771), and Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers
Subjects: Pharmacology, Pharmacovigilance, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Adverse drug reaction, Drug shortage, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pharmacology (medical), Medication error
Abstract: International audience; AIM: Drug shortage is a growing global health issue. The aim of the study was to evaluate the consequences of drug shortages on patient safety based on data recorded in the French Pharmacovigilance Database. METHODS: All cases involving drug shortages reported from 1985 to the end of 2019 were extracted from the database. RESULTS: Following the selection process, 462 cases were included. The number of cases increased significantly from 2004 to 2019. Cases mainly involved drugs from the nervous system (22.1%, CI95[17.5;27.0]), the cardiovascular system (16.4%, CI95[11.9;21.4]), and anti-infectives for systemic use (14.3%, CI95[9.7;19.2]) ATC classes. Most of the cases reported an adverse drug reaction (ADR) belonging to the SOC nervous system (21%, CI95[18;24]), skin and subcutaneous (14%, CI95[11;17]), general (13%, CI95[10;17]), and gastrointestinal (8%, CI95[5;11]) disorders. Disease worsening was observed in 15.9% of the cases, mostly related to a lack of efficacy of the replacement drug. Half of the cases were considered as serious. Evolution was favourable in 79.4% of the cases. Death and/or life-threatening situations were reported in 5.8% of the cases. Medication errors (ME) were identified in 51 cases (11%), mostly occurring at the administration step and involving a human factor. CONCLUSION: This study emphasises the clinical impact of drug shortage in terms of ADRs, ME and inefficiency. These observations underline the importance of a global health policy programme to limit the occurrence of drug shortages and to reinforce the information provided to patients and health care professionals in this context to limit risk.
Published: 2022

34. Can Dopamine Responsiveness Be Predicted in Parkinson’s Disease Without an Acute Administration Test?

Author: Betrouni, Nacim, Moreau, Caroline, Rolland, Anne-Sophie, Carrière, Nicolas, Viard, Romain, Lopes, Renaud, Kuchcinski, Gregory, Eusebio, Alexandre, Thobois, Stephane, Hainque, Elodie, Hubsch, Cecile, Rascol, Olivier, Brefel, Christine, Drapier, Sophie, Giordana, Caroline, Durif, Franck, Maltête, David, Guehl, Dominique, Hopes, Lucie, Rouaud, Tiphaine, Jarraya, Bechir, Benatru, Isabelle, Tranchant, Christine, Tir, Melissa, Chupin, Marie, Bardinet, Eric, Defebvre, Luc, Corvol, Jean-Christophe, Devos, David, 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), 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 ), École des Hautes Études en Santé Publique [EHESP] (EHESP), CHU Lille, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 (PLBS), 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)-Centre National de la Recherche Scientifique (CNRS), CHU Marseille, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), 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), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Service de Neurologie [CHU Nice], Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, 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), CHU Rouen, Normandie Université (NU), CHU Bordeaux [Bordeaux], Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Amiens-Picardie, Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), and Université de Picardie Jules Verne (UPJV)
Subjects: Antiparkinson Agents, Levodopa, Cellular and Molecular Neuroscience, Dopamine, [SCCO.NEUR]Cognitive science/Neuroscience, Humans, Parkinson Disease, Neurology (clinical), Magnetic Resonance Imaging
Abstract: Background: Dopamine responsiveness (dopa-sensitivity) is an important parameter in the management of patients with Parkinson’s disease (PD). For quantification of this parameter, patients undergo a challenge test with acute Levodopa administration after drug withdrawal, which may lead to patient discomfort and use of significant resources. Objective: Our objective was to develop a predictive model combining clinical scores and imaging. Methods: 350 patients, recruited by 13 specialist French centers and considered for deep brain stimulation, underwent an acute L-dopa challenge (dopa-sensitivity > 30%), full assessment, and MRI investigations, including T1w and R2* images. Data were randomly divided into a learning base from 10 centers and data from the remaining centers for testing. A machine selection approach was applied to choose the optimal variables and these were then used in regression modeling. Complexity of the modelling was incremental, while the first model considered only clinical variables, the subsequent included imaging features. The performances were evaluated by comparing the estimated values and actual values Results: Whatever the model, the variables age, sex, disease duration, and motor scores were selected as contributors. The first model used them and the coefficients of determination (R2) was 0.60 for the testing set and 0.69 in the learning set (p
Published: 2022

35. Natural speech comprehension in bipolar disorders: An event-related brain potential study among manic patients

Author: Jean-Arthur Micoulaud-Franchi, Michel Cermolacce, Jean-Michel Azorin, Jean Naudin, M. Maurel, Mélanie Faugere, Raoul Belzeaux, Jean Vion-Dury, Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Département Universitaire de Psychiatrie - [Hôpital Sainte Marguerite - APHM] (Hôpitaux Sud), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Unité de Neurophysiologie, Psychophysiologie et Neurophénoménologie, Centre Hospitalier Universitaire de Sainte-Marguerite, Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pôle de psychiatrie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-CHU Marseille, Fondation FondaMental [Créteil], Pôle de Psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-CHU Marseille, Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), and Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )
Subjects: Adult, Male, Bipolar Disorder, Speech perception, genetic structures, Context (language use), behavioral disciplines and activities, [SCCO]Cognitive science, Young Adult, medicine, Humans, Semantic memory, Bipolar disorder, Evoked Potentials, Late positive component, ComputingMilieux_MISCELLANEOUS, [SCCO.NEUR]Cognitive science/Neuroscience, Cognition, Middle Aged, medicine.disease, N400, Semantics, Psychiatry and Mental health, Clinical Psychology, Mood disorders, Case-Control Studies, Speech Perception, Female, Psychology, Cognitive psychology
Abstract: Background Thought and language disturbances are crucial clinical features in Bipolar Disorders (BD), and constitute a fundamental basis for social cognition. In BD, clinical manifestations such as disorganization and formal thought disorders may play a role in communication disturbances. However, only few studies have explored language disturbances in BD at a neurophysiological level. Two main Event-Related brain Potentials (ERPs) have been used in language comprehension research: the N400 component, elicited by incongruous word with the preceding semantic context, and the Late Positive Component (LPC), associated with non-specifically semantic and more general cognitive processes. Previous studies provided contradictory results regarding N400 in mood disorders, showing either preserved N400 in depression or dysthymia, or altered N400 in BD during semantic priming paradigm. The aim of our study was to explore N400 and LPC among patients with BD in natural speech conditions. Methods ERPs from 19 bipolar type I patients with manic or hypomanic symptomatology and 19 healthy controls were recorded. Participants were asked to listen to congruous and incongruous complete sentences and to judge the match between the final word and the sentence context. Behavioral results and ERPs data were analyzed. Results At the behavioral level, patients with BD show worst performances than healthy participants. At the electrophysiological level, our results show preserved N400 component in BD. LPC elicited under natural speech conditions shows preserved amplitude but delayed latency in difference waves. Limitations Small size of samples, absence of schizophrenic group and medication status. Conclusions In contrast with the only previous N400 study in BD that uses written semantic priming, our results show a preserved N400 component in ecological and natural speech conditions among patients with BD. Possible implications in terms of clinical specificity are discussed.
Published: 2014

36. Predictive factors of non-operative management failure in 494 blunt liver injuries: a multicenter retrospective study

Author: Mathieu Rouy, Clément Julien, Ilyes Hamouda, Damien Massalou, Thierry Bege, Marc Leone, Stephane Berdah, Sandrine Barbois, Edouard Girard, Catherine Arvieux, David Jérémie Birnbaum, Équipe de droit international, européen et comparé (EDIEC), Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Emergency surgery, CHU Nice, Laboratoire de Biomécanique Appliquée (LBA UMR T24), Aix Marseille Université (AMU)-Université Gustave Eiffel, Université Côte d'Azur (UCA), CHU Marseille, Hôpital Nord [CHU - APHM], Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Centre Hospitalier Universitaire [Grenoble] (CHU), and Assistance Publique - Hôpitaux de Marseille (APHM)
Subjects: Liver, Hemoperitoneum, Humans, Surgery, Prospective Studies, Wounds, Nonpenetrating, Retrospective Studies, [SHS]Humanities and Social Sciences
Abstract: Non-operative management (NOM) has become the major treatment of blunt liver trauma (BLT) with a NOM failure rate of 3-15% due to liver-related complications. The aim of the study was to determine the predictive factors and a risk-stratified score of NOM failure. From 2013 to 2021, all patients with BLT in three trauma centers were included; clinical, biological, radiological and outcome data were retrospectively analyzed. Predictive factors and a risk-stratified score associated with NOM failure were identified. Four hundred and ninety-four patients with BLT were included. Among them, 80 (16.2%) had isolated BLT. Fifty-nine patients (11.9%) underwent emergent operative management (OM) on the day of admission and 435 (88.1%) had a NOM. NOM failure rate was 11.5%. Patients with a NOM failure more frequently had a hemoperitoneum (p 0.001), liver bleeding (p 0.001), blood transfusion (p 0.001) and angioembolization (p 0.001) compared to patient with a successful NOM. In multivariate analysis, the presence of hemoperitoneum (OR = 5.71; 95 CI [1.29-25.45]), angioembolization (OR = 8.73; 95 CI [2.04-38.44] and severe liver injury (AAST IV or V) (OR = 8.97; 95 CI [3.36-23.99]) were independent predictive factors of NOM failure. When these three factors were associated, NOM failure rate was 83.3%. The AAST grade, the presence of hemoperitoneum and the realization of liver angioembolization on the day of admission are three independent predictive factors of NOM failure. Our risk-score based on these three factors stratify the risk of NOM failure in BLT and could be used for a more appropriate level of medical survey adapted to each patient. Level of evidence: prospective observational cohort study, Level III.
Published: 2022

37. A focus on dominant negative variants in a series of 170 heterozygous FXI-deficient patients

Author: de Mazancourt, Philippe, Quélin, Florence, Flaujac, Claire, de Raucourt, Emmanuelle, Guillet, B, Bauduer, Frédéric, Ernest, Vincent, Beurrier, Philippe, Avril, Aurélie, D’oiron, Roseline, Biron-Andreani, Christine, Meunier, Sandrine, Dargaud, Yesim, Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier de Versailles André Mignot (CHV), 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 ), École des Hautes Études en Santé Publique [EHESP] (EHESP), De la Préhistoire à l'Actuel : Culture, Environnement et Anthropologie (PACEA), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier de la Côte Basque (CHCB), CHU Marseille, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Lapeyronie [Montpellier] (CHU), Hôpital Louis Pradel [CHU - HCL], and Hospices Civils de Lyon (HCL)
Subjects: dominant negative variant, [SDV]Life Sciences [q-bio], FXI deficiency, HPO 0001928 Abnormality of coagulation, HPO 0003256 Abnormality of the coagulation cascade, F11 variant, F11 gene
Abstract: International audience; INTRODUCTION: Dominant-negative effects have been described for 10 F11 variants in the literature. AIM: The current study aimed at identifying putative dominant-negative F11 variants. MATERIAL AND METHODS: This research consisted in a retrospective analysis of routine laboratory data. RESULTS: In a series of 170 patients with moderate/mild factor XI (FXI) deficiencies, we identified heterozygous carriers of previously reported dominant-negative variants (p.Ser243Phe, p.Cys416Tyr, and p.Gly418Val) with FXI activities inconsistent with a dominant-negative effect. Our findings also do not support a dominant-negative effect of p.Gly418Ala. We also identified a set of patients carrying heterozygous variants, among which five out of 11 are novel, with FXI activities suggesting a dominant-negative effect (p.His53Tyr, p.Cys110Gly, p.Cys140Tyr, p.Glu245Lys, p.Trp246Cys, p.Glu315Lys, p.Ile421Thr, p.Trp425Cys, p.Glu565Lys, p.Thr593Met, and p.Trp617Ter). However, for all but two of these variants, individuals with close to half normal FXI coagulant activity (FXI:C) were identified, indicating an inconstant dominant effect. CONCLUSION: Our data show that for some F11 variants recognized has having dominant-negative effects, such effects actually do not occur in many individuals. The present data suggest that for these patients, the intracellular quality control mechanisms eliminate the variant monomeric polypeptide before homodimer assembly, thereby allowing only the wild-type homodimer to assemble and resulting in half normal activities. In contrast, in patients with markedly decreased activities, some mutant polypeptides might escape this first quality control. In turn, assembly of heterodimeric molecules as well as mutant homodimers would result in activities closer to 1:4 of FXI:C normal range.
Published: 2023

38. Primary Non-Aortic Lesions Are Not Rare in Marfan Syndrome and Are Associated with Aortic Dissection Independently of Age

Author: Jean Sénémaud, Marine Gaudry, Elisabeth Jouve, Arnaud Blanchard, Olivier Milleron, Yves Dulac, Laurence Olivier-Faivre, Dominique Stephan, Sylvie Odent, Damien Lanéelle, Sophie Dupuis-Girod, Guillaume Jondeau, Laurence Bal-Theoleyre, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Marseille, Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Strasbourg, CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), and None
Subjects: ectasia, Marfan syndrome, [SDV.GEN]Life Sciences [q-bio]/Genetics, non-aortic aneurysm, aortic dissection, General Medicine
Abstract: International audience; PURPOSE: The study sought to estimate the prevalence of primary non-aortic lesions (PNAL) unrelated to extension of aortic dissection (AD) in a cohort of patients with Marfan syndrome (MFS). METHODS: Adult patients presenting with pathogenic FBN1 mutations and an available pan-aortic contrast-enhanced CTA in eight French MFS clinics from April to October 2018 were included. Clinical and radiological data, particularly the presence of aortic lesions and PNAL (including aneurysm and ectasia), were retrospectively analyzed. RESULTS: Out of 138 patients, 28 (20.3%) had PNAL. In total, 27 aneurysms in 13 patients and 41 ectasias in 19 patients were reported mainly in the subclavian, iliac, and vertebral segments. Four patients (31%) with aneurysms and none with ectasia required prophylactic intervention during follow-up (median: 46 months). In multivariate analysis, factors associated with PNAL were history of AD (OR = 3.9, 95%CI: 1.3-12.1, p = 0.018), history of previous descending aortic surgery (OR = 10.3, 95%CI: 2.2-48.3, p = 0.003) and age (per 10 years OR = 1.6, 95%CI: 1.1-2.4, p = 0.008). CONCLUSION: PNAL is not rare in MFS patients with evolutive aortic disease. Natural history may differ between aneurysms and ectasia, emphasizing the need for standardized definitions and systematic screening for PNAL.
Published: 2023
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39. Determinants of long-term outcomes in patients with COVID-19 supported with ECMO

Author: Christophe Guervilly, Marco Giani, Nicolas Nesseler, Matthieu Schmidt, Sami Hraiech, CHU Marseille, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), 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), 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], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Pulmonary and Respiratory Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
Abstract: International audience
Published: 2023

40. Human Polyomavirus-6 Infecting Lymph Nodes of a Patient With an Angiolymphoid Hyperplasia With Eosinophilia or Kimura Disease

Author: Jean-Jacques Grob, Anne-Marie Collet-Villette, Didier Raoult, Caroline Gaudy-Marqueste, Christelle Desnues, M. Penicaud, Sonia Bouchard, Nicolás Rascovan, Hubert Lepidi, Hôpital de la Timone [CHU - APHM] (TIMONE), Département de dermatologie, CHU Marseille, CHU Marseille, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), and Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Microbiology (medical), Pathology, medicine.medical_specialty, education, medicine.disease_cause, 03 medical and health sciences, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Skin surface, medicine, Humans, Angiolymphoid hyperplasia with eosinophilia, Lymph node, Human polyomavirus 6, Polyomavirus Infections, business.industry, Angiolymphoid Hyperplasia with Eosinophilia, Middle Aged, medicine.disease, 3. Good health, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, Healthy individuals, Immunology, Metagenome, Female, Kimura Disease, Lymph Nodes, Lymph, Polyomavirus, business
Abstract: International audience; Human polyomavirus 6 (HPyV6) is most often detected at the skin surface of healthy individuals. Here, we demonstrate for the first time that HPyV6 also infects internal tissues. We provide direct evidence of HPyV6 infecting a lymph node of a patient with an angiolymphoid hyperplasia with eosinophilia or Kimura disease.
Published: 2016

41. Postpartum hemorrhage: guidelines for clinical practice from the French ă College of Gynaecologists and Obstetricians (CNGOF) in collaboration ă with the French Society of Anesthesiology and Intensive Care (SFAR)

Author: Sentilhes , Loïc, Vayssière , Christophe, Deneux-Tharaux , Catherine, Aya , Antoine Guy, Bayoumeu , Francoise, Bonnet , Marie-Pierre, Djoudi , Rachid, Dolley , Patricia, Dreyfus , Michel, Ducroux-Schouwey , Chantal, Dupont , Corinne, François , Anne, Gallot , Denis, Haumonté , Jean-Baptiste, Huissoud , Cyril, Kayem , Gilles, Keïta , Hawa, Langer , Bruno, Mignon , Alexandre, Morel , Olivier, Parant , Olivier, Pelage , Jean-Pierre, Phan , Emmanuelle, Rossignol , Mathias, Tessier , Véronique, Mercier , Frederic J., Goffinet , François, Service d'Obstétrique et Gynécologique [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), 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 de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants (UMR_S 953), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Gynécologie-Obstétrique et Médecine de la Reproduction [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), Clinatec - Centre de recherche biomédicale Edmond J.Safra (SCLIN), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Santé Individu Société (SIS), Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Réseau périnatal Aurore, Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Gynécologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Retinoids, Development and Developmental Diseases (R2D2), Université d'Auvergne - Clermont-Ferrand I (UdA), Service d'Obstétrique-Gynécologie [Marseille], Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille- Hôpital Nord [CHU - APHM], Institut cellule souche et cerveau (SBRI), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-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), Service d'Anesthésie-Réanimation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de gynécologie–obstétrique, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service Gynécologie [CHU Toulouse], Pôle Femme-Mère-Couple [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Ambroise Paré, Department of Interventional Radiology, Assistance Publique - Hôpitaux de Paris, Sciences et Technologies de la Musique et du Son (STMS), Institut de Recherche et Coordination Acoustique/Musique (IRCAM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Réseau périnatal port-royal, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Saint-Vincent de Paul, Service de Gynécologie et Obstétrique [Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Sud - Paris 11 (UP11), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Santé Individu Société - SIS (SIS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université Lumière - Lyon 2 (UL2), Institut cellule souche et cerveau (U846 Inserm - UCBL1), Service de Gynécologie-Obstétrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de gynécologie obstétrique, CHU Toulouse [Toulouse]-Hôpital Paule de Viguier, CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Clinatec - Centre de recherche biomédicale Edmond J.Safra, Université Joseph Fourier - Grenoble 1 (UJF)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle de Gynécologie-Obstétrique et Reproduction Humaine, CHU Clermont-Ferrand-Université de Clermont-Ferrand, Institut cellule souche et cerveau / Stem Cell and Brain Research Institute (SBRI), Université Claude Bernard Lyon 1 (UCBL), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Université Pierre et Marie Curie - Paris 6 (UPMC)-IRCAM-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Saint-Vincent de Paul, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Université de Montpellier (UM)-Université Montpellier 1 (UM1), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre hospitalier universitaire d'Angers, Épidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps, Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants ( UMR_S 953 ), Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Gynécologie - Obstétrique et médecine de la reproduction [Caen], Université Joseph Fourier - Grenoble 1 ( UJF ) -Centre Hospitalier Universitaire [Grenoble] ( CHU ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Santé Individu Société - SIS ( SIS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Hospices Civils de Lyon ( HCL ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Université Jean Moulin - Lyon III ( UJML ) -Université Lumière - Lyon 2 ( UL2 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Retinoids, Development and Developmental Diseases ( R2D2 ), Université d'Auvergne - Clermont-Ferrand I ( UdA ), Assistance Publique - Hôpitaux de Marseille ( APHM ) -CHU Marseille- Hôpital Nord [CHU - APHM], Institut cellule souche et cerveau / Stem Cell and Brain Research Institute ( SBRI ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique ( CRESS - U1153 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Sciences et Technologies de la Musique et du Son ( STMS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IRCAM-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Saint-Vincent de Paul, and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]
Subjects: [ SHS.PSY ] Humanities and Social Sciences/Psychology, [ SDV.MHEP.PSM ] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Quality of Life, [ SHS.ECO ] Humanities and Social Sciences/Economies and finances, [SHS.PSY]Humanities and Social Sciences/Psychology, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SHS.ECO]Humanities and Social Sciences/Economics and Finance
Abstract: International audience; Postpartum haemorrhage (PPH) is defined as blood loss >= 500 mL after ă delivery and severe PPH as blood loss >= 1000 mL, regardless of the ă route of delivery (professional consensus). The preventive ă administration of uterotonic agents just after delivery is effective in ă reducing the incidence of PPH and its systematic use is recommended, ă regardless of the route of delivery (Grade A). Oxytocin is the first ă line prophylactic drug, regardless of the route of delivery (Grade A); a ă slowly dose of 5 or 10 IU can be administered (Grade A) either IV or IM ă (professional consensus).After vaginal delivery, routine cord drainage ă (Grade B), controlled cord traction (Grade A), uterine massage (Grade ă A), and routine bladder voiding (professional consensus) are not ă systematically recommended for PPH prevention. After caesarean delivery, ă placental delivery by controlled cord traction is recommended (grade B). ă The routine use of a collector bag to assess postpartum blood loss at ă vaginal delivery is not systematically recommended (Grade B), since the ă incidence of severe PPH is not affected by this intervention. In cases ă of overt PPH after vaginal delivery, placement of a blood collection bag ă is recommended (professional consensus). The initial treatment of PPH ă consists in a manual uterine examination, together with antibiotic ă prophylaxis, careful visual assessment of the lower genital tract, a ă uterine massage, and the administration of 5-10 IU oxytocin injected ă slowly IV or IM, followed by a maintenance infusion not to exceed a ă cumulative dose of 40 IU (professional consensus). If oxytocin fails to ă control the bleeding, the administration of sulprostone is recommended ă within 30 minutes of the PPH diagnosis (Grade C). Intrauterine balloon ă tamponade can be performed if sulprostone fails and before recourse to ă either surgery or interventional radiology (professional consensus). ă Fluid resuscitation is recommended for PPH persistent after first line ă uterotonics, or if clinical signs of severity (Grade B). The objective ă of RBC transfusion is to maintain a haemoglobin concentration (Hb) >8 ă g/dL. During active haemorrhaging, it is desirable to maintain a ă fibrinogen level >= 2 g/L (professional consensus). RBC, fibrinogen and ă fresh frozen plasma (FFP) may be administered without awaiting ă laboratory results (professional consensus). Tranexamic acid may be used ă at a dose of 1 g, renewable once if ineffective the first time in the ă treatment of PPH when bleeding persists after sulprostone administration ă (professional consensus), even though its clinical value has not yet ă been demonstrated in obstetric settings. It is recommended to prevent ă and treat hypothermia in women with PPH by warming infusion solutions ă and blood products and by active skin warming (Grade C). Oxygen ă administration is recommended in women with severe PPH (professional ă consensus). If PPH is not controlled by pharmacological treatments and ă possibly intra-uterine balloon, invasive treatments by arterial ă embolization or surgery are recommended (Grade C). No technique for ă conservative surgery is favoured over any other (professional ă consensus). Hospital-to-hospital transfer of a woman with a PPH for ă embolization is possible once hemoperitoneum is ruled out and if the ă patient's hemodynamic condition so allows (professional consensus). (C) ă 2015 Elsevier Ireland Ltd. All rights reserved.
Published: 2016

42. Postpartum hemorrhage: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians (CNGOF): in collaboration with the French Society of Anesthesiology and Intensive Care (SFAR)

Author: Loïc, Sentilhes, Christophe, Vayssière, Catherine, Deneux-Tharaux, Antoine Guy, Aya, Françoise, Bayoumeu, Marie-Pierre, Bonnet, Rachid, Djoudi, Patricia, Dolley, Michel, Dreyfus, Chantal, Ducroux-Schouwey, Corinne, Dupont, Anne, François, Denis, Gallot, Jean-Baptiste, Haumonté, Cyril, Huissoud, Gilles, Kayem, Hawa, Keita, Bruno, Langer, Alexandre, Mignon, Olivier, Morel, Olivier, Parant, Jean-Pierre, Pelage, Emmanuelle, Phan, Mathias, Rossignol, Véronique, Tessier, Frédéric J, Mercier, François, Goffinet, Service de Gynécologie-Obstétrique, CHU Bordeaux, 33076 Bordeaux, France, CHU Bordeaux [Bordeaux], Service de Gynécologie-Obstétrique, Hôpital Paule de Viguier, CHU Toulouse, 31059 Toulouse, France, UMR 1027 Inserm Université Toulouse III « Epidémiologie Périnatale et handicap de l'enfant, Santé des adolescents », 31000 Toulouse, France., Centre Hospitalier Universitaire de Toulouse - CHU Toulouse (FRANCE), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5) - Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A 1125)), Institut National de la Recherche Agronomique (INRA) - Université Sorbonne Paris Cité (USPC) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Institut National de la Recherche Agronomique (INRA) - Université Sorbonne Paris Cité (USPC) - Institut National de la Santé et de la Recherche Médicale (INSERM), Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1) - Université de Montpellier (UM), CHU de Toulouse, Pole d'anesthésie Réanimation, Hôpital Paule de Viguier, Toulouse F-31059, France, CHU Toulouse [Toulouse], Service d'Anesthésie-Réanimation (COCHIN - Anesthésie-Réanimation), Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris Descartes - Paris 5 (UPD5), Etablissement Français du Sang, 20, Avenue du Stade de France, 93218 La Plaine Saint-Denis Cedex, France, Etablissement Français du Sang (EFS), Service de Gynécologie-Obstétrique, CHU Caen et UFR de Médecine Caen, 14033 Caen, France., CHU Caen, Service de Gynécologie-Obstétrique, CHU Caen et UFR de Médecine Caen, 14033 Caen, France, UFR de Médecine Caen, 14033 Caen, France., Association d'usagers, Collectif interassociatif autour de la naissance (CIANE), Paris, France, Réseau périnatal Aurore - Hôpital de la Croix Rousse, université Lyon 1, Lyon, France, EA 4129, laboratoire « Santé, individu, société », faculté de médecine Laennec, 69372 Lyon, France., Université Claude Bernard Lyon 1 (UCBL), Université de Lyon - Université de Lyon, Etablissement Français du Sang Ile de France, site de l'Hôpital Européen Georges-Pompidou, APHP, Paris, France., Service de Gynécologie-Obstétrique, CHU Estaing [Clermont-Ferrand], Service de Gynécologie-Obstétrique, CHU Marseille, Hôpital Nord, AP-HM, 13015 Marseille, France., CHU Marseille, INSERM U846, Stem Cell and Brain Research Institute, Lyon, France., Service de Gynécologie-Obstétrique, Hôpital Louis-Mourier, AP-HP, 92701 Colombes, France., Hopital Louis Mourier - AP-HP [Colombes], Service d'Anesthésie, CHU Louis-Mourier, AP-HP/Université Paris-7, 178, rue des Renouilliers, 92700 Colombes, France, Université Paris-Diderot, Sorbonne Paris Cité, EA recherche clinique coordonnée ville-hôpital, méthodologies et société (REMES), 75010 Paris, France., CHU Louis Mourrier, Département de Gynécologie-Obstétrique, Hôpital de Hautepierre, Avenue Molière, 67098 Strasbourg, France., Hôpital de Hautepierre [Strasbourg], Service d'Obstétrique et de Médecine fœtale [CHRU Nancy], Pôle de Gynécologie-Obstétrique et Reproduction, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy) - Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy) - Université de Lorraine (UL), Inserm, UMR1027, Toulouse F-31073, France, Université de Toulouse III, UMR1027, Toulouse F-31073, France, CHU Toulouse, Pole de Gynécologie Obstétrique, Hôpital Paule de Viguier, Toulouse F-31059, France., Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Radiologie, CHU Caen, 14033 Caen, France., Département d'Anesthésie Réanimation SMUR [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) - Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], DHU Risques Et Grossesse, Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Société Française d'Anesthésie et de Réanimation, France, Département d'Anesthésie, Hôpital Antoine Béclère, APHP, Clamart, France, Faculté de Médecine de K. Bicêtre, Université Paris-Sud, France., Hôpital Antoine-Béclère AP-HP, and AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris]
Subjects: Postpartum hemorrhage, [SDV] Life Sciences [q-bio], Pregnancy, Oxytocics, Placenta accreta, Transfusion, Humans, Female, Peripartum hysterectomy, Delivery, Obstetric, Oxytocin
Abstract: International audience; Postpartum haemorrhage (PPH) is defined as blood loss ≥500mL after delivery and severe PPH as blood loss ≥1000mL, regardless of the route of delivery (professional consensus). The preventive administration of uterotonic agents just after delivery is effective in reducing the incidence of PPH and its systematic use is recommended, regardless of the route of delivery (Grade A). Oxytocin is the first-line prophylactic drug, regardless of the route of delivery (Grade A); a slowly dose of 5 or 10 IU can be administered (Grade A) either IV or IM (professional consensus). After vaginal delivery, routine cord drainage (Grade B), controlled cord traction (Grade A), uterine massage (Grade A), and routine bladder voiding (professional consensus) are not systematically recommended for PPH prevention. After caesarean delivery, placental delivery by controlled cord traction is recommended (grade B). The routine use of a collector bag to assess postpartum blood loss at vaginal delivery is not systematically recommended (Grade B), since the incidence of severe PPH is not affected by this intervention. In cases of overt PPH after vaginal delivery, placement of a blood collection bag is recommended (professional consensus). The initial treatment of PPH consists in a manual uterine examination, together with antibiotic prophylaxis, careful visual assessment of the lower genital tract, a uterine massage, and the administration of 5-10 IU oxytocin injected slowly IV or IM, followed by a maintenance infusion not to exceed a cumulative dose of 40IU (professional consensus). If oxytocin fails to control the bleeding, the administration of sulprostone is recommended within 30minutes of the PPH diagnosis (Grade C). Intrauterine balloon tamponade can be performed if sulprostone fails and before recourse to either surgery or interventional radiology (professional consensus). Fluid resuscitation is recommended for PPH persistent after first line uterotonics, or if clinical signs of severity (Grade B). The objective of RBC transfusion is to maintain a haemoglobin concentration (Hb) >8g/dL. During active haemorrhaging, it is desirable to maintain a fibrinogen level ≥2g/L (professional consensus). RBC, fibrinogen and fresh frozen plasma (FFP) may be administered without awaiting laboratory results (professional consensus). Tranexamic acid may be used at a dose of 1 g, renewable once if ineffective the first time in the treatment of PPH when bleeding persists after sulprostone administration (professional consensus), even though its clinical value has not yet been demonstrated in obstetric settings. It is recommended to prevent and treat hypothermia in women with PPH by warming infusion solutions and blood products and by active skin warming (Grade C). Oxygen administration is recommended in women with severe PPH (professional consensus). If PPH is not controlled by pharmacological treatments and possibly intra-uterine balloon, invasive treatments by arterial embolization or surgery are recommended (Grade C). No technique for conservative surgery is favoured over any other (professional consensus). Hospital-to-hospital transfer of a woman with a PPH for embolization is possible once hemoperitoneum is ruled out and if the patient's hemodynamic condition so allows (professional consensus).
Published: 2016

43. The Prevalence of Mental Disorders Among Children and Adolescents in the Child Welfare System: A Systematic Review and Meta-Analysis

Author: Guillaume Fond, Laurent Boyer, Anderson Loundou, Marine Alessandrini, Sylvie Tordjman, Pascal Auquier, Guillaume Bronsard, Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants (SPMC), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), INSERM U955, équipe 15, Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Réseau de coopération scientifique en santé mentale, Fondation FondaMental [Créteil]-Fondation FondaMental [Créteil]-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Unité d'Aide Méthodologique, Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Service Psychiatrie de l'Enfant et de l'Adolescent, CHU Pontchaillou [Rennes]-Centre Hospitalier Guillaume Régnier [Rennes]-CHS (Centre Hospitalier Spécialisé lutte Maladies Mentales), Audition (Psychophysique, Modélisation, Neurosciences) (APMN), Laboratoire des systèmes perceptifs (LSP), Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Département d'Etudes Cognitives - ENS Paris (DEC), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Réseau de coopération scientifique en santé mentale, Centre National de la Recherche Scientifique (CNRS)-Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS)-Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants ( SPMC ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Réseau de coopération scientifique en santé mentale, Fondation FondaMental [Créteil]-Fondation FondaMental [Créteil]-Institut Mondor de Recherche Biomédicale ( IMRB ), Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10, Assistance Publique - Hôpitaux de Marseille ( APHM ) -CHU Marseille, Audition (Psychophysique, Modélisation, Neurosciences) ( APMN ), Laboratoire des systèmes perceptifs, Département d'Etudes Cognitives - ENS Paris ( DEC ), École normale supérieure - Paris ( ENS Paris ) -École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ) -Département d'Etudes Cognitives - ENS Paris ( DEC ), École normale supérieure - Paris ( ENS Paris ) -École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ), Centre méditérannéen de médecine moléculaire ( C3M ), Université Nice Sophia Antipolis ( UNS ), and Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: [ SDV.MHEP.PSM ] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SHS.PSY]Humanities and Social Sciences/Psychology, 0302 clinical medicine, Epidemiology, Prevalence, [ SHS.ECO ] Humanities and Social Sciences/Economies and finances, 030212 general & internal medicine, Child, education.field_of_study, Mental Disorders, 05 social sciences, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, General Medicine, 16. Peace & justice, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, Quality, Anxiety Disorders, 3. Good health, Observational Studies as Topic, Conduct disorder, Meta-analysis, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Anxiety, medicine.symptom, 050104 developmental & child psychology, Research Article, Conduct Disorder, medicine.medical_specialty, Adolescent, Population, MEDLINE, Child Welfare, [ SHS.PSY ] Humanities and Social Sciences/Psychology, 03 medical and health sciences, Prevalence of mental disorders, medicine, Humans, 0501 psychology and cognitive sciences, Psychiatry, education, Depressive Disorder, business.industry, medicine.disease, Confidence interval, Attention Deficit Disorder with Hyperactivity, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Meta-Analysis of Observe Studies In Epidemiology
Abstract: Supplemental Digital Content is available in the text, It remains unclear whether children and adolescents in the child welfare system (CWS) exhibit a higher prevalence of mental disorders compared with the general population. The objective of this study was to perform a systematic review and meta-analysis to assess the prevalence of mental disorders in the CWS. All of the epidemiological surveys assessing the prevalence of mental disorders in children and adolescents in the CWS were included. The pooled prevalence was estimated with random effect models. Potential sources of heterogeneity were explored using meta-regression analyses. Eight studies provided prevalence estimates that were obtained from 3104 children and adolescents. Nearly 1 child or adolescent of every 2 (49%; 95% confidence interval (CI) 43–54) was identified as meeting criteria for a current mental disorder. The most common mental disorder was disruptive disorder (27%; 95% CI 20–34), including conduct disorder (20%; 95% CI 13–27) and oppositional defiant disorder (12%; 95% CI 10–14). The prevalence of attention-deficit/hyperactivity disorder was estimated to be 11% (95% CI 6–15). The prevalence estimates of anxiety and depressive disorders were 18% (95% CI 12–24) and 11% (95% CI 7–15). Posttraumatic stress disorder had the lowest prevalence (4%; 95% CI 2–6). High prevalences of mental disorders in the CWS were reported, which highlights the need for the provision of qualified service. The substantial heterogeneity of our findings is indicative of the need for accurate epidemiological data to effectively guide public policy.
Published: 2016

44. Bilobectomy for lung cancer: contemporary national early morbidity and mortality outcomes

Author: Anderson Loundou, Françoise Le Pimpec-Barthes, Pascal Thomas, Jacques Jougon, Pierre-Emmanuel Falcoz, Gilbert Massard, Laurent Brouchet, Alain Bernard, Marcel Dahan, Epithor Grp, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, Service de chirurgie cardio-vasculaire et thoracique (CHU Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de chirurgie thoracique [AP-HP HEGP, Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Institut des Maladies Métaboliques et Cardiovasculaires (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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Unité d'Aide Méthodologique, Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes ( URMITE ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR48, INSB-INSB-Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche en Communications et en Cybernétique de Nantes ( IRCCyN ), Mines Nantes ( Mines Nantes ) -École Centrale de Nantes ( ECN ) -Ecole Polytechnique de l'Université de Nantes ( Polytech Nantes ), Université de Nantes ( UN ) -Université de Nantes ( UN ) -PRES Université Nantes Angers Le Mans ( UNAM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ), Institut des Maladies Métaboliques et Cardiovasculaires ( I2MC ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and Assistance Publique - Hôpitaux de Marseille ( APHM ) -CHU Marseille
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Lung Neoplasms, medicine.medical_treatment, Operative Time, 030204 cardiovascular system & hematology, 03 medical and health sciences, Bilobectomy, Pneumonectomy, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Carcinoma, Non-Small-Cell Lung, Medicine, Humans, Prospective Studies, Lung cancer, Aged, 2. Zero hunger, Performance status, business.industry, Thoracic Surgery, Video-Assisted, General Medicine, Odds ratio, Middle Aged, Pleural Diseases, medicine.disease, Confidence interval, 3. Good health, Surgery, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Treatment Outcome, Cardiothoracic surgery, Cardiovascular Diseases, 030220 oncology & carcinogenesis, Female, Bronchial Fistula, France, Cardiology and Cardiovascular Medicine, business, Body mass index
Abstract: 23rd European Conference on General Thoracic Surgery, Lisbon, PORTUGAL, MAY 31-JUN 03, 2015; International audience; To determine contemporary early outcomes associated with bilobectomy for lung cancer and to identify their predictors using a nationally representative general thoracic surgery database. A total of 1831 patients, who underwent elective bilobectomy for primary lung cancer between 1 January 2004 and 31 December 2013, were selected. Logistic regression analysis was performed on variables for major adverse events. There were 670 upper and 1161 lower bilobectomies. Video-assisted thoracic surgery was seldom performed (2%). Induction therapy and extended resection were performed in 293 (16%) and 279 patients (15.2%), respectively. Operative mortality was 4.8% (upper: 4.5%/lower: 5%; P = 0.62), and significantly higher following extended procedures when compared with standard bilobectomy (4.3 vs 7.5%; P = 0.013). Pulmonary complication rate was 21.1%. Bronchial fistula occurred in 46 patients (2.5%) and pleural space complications in 296 (16.2%). Their respective incidence rates were significantly higher following lower than upper bilobectomy (3.5 vs 0.7%; P < 0.001 and 17.8 vs 13.3%; P = 0.007). At multivariate analysis, extended procedures [odds ratio (OR), 2.3; 95% confidence interval (CI), 1.03-5.31; P = 0.04], ASA scores of 3 or greater (OR, 2.02; 95% CI, 1.33-3.07; P < 0.001) and World Health Organization performance status 2 or greater (OR, 1.47; 95% CI, 1.01-2.13; P = 0.04) were risk predictors of mortality. Female gender (OR, 0.39; 95% CI, 0.19-0.80; P = 0.01), highest body mass index (BMI) values (OR, 0.91; 95% CI, 0.86-0.96; P = 0.001) and recent years of surgery (OR, 0.91; 95% CI, 0.84-0.99; P = 0.02) were protective. Predictors of bronchial fistula were male gender, lowest BMI values, lower bilobectomy and longest operative times. Male gender, lowest BMI values and longest operative times were also predictors of pulmonary complications, together with highest ASA scores and lowest forced expiratory volume in 1 s values. Risks related to lower bilobectomy lie halfway between those reported for lobectomy and pneumonectomy. Additional surgical measures to prevent pleural space complications and bronchial fistula should be encouraged with this operation. In contrast, upper bilobectomy shares more or less the same hazards as lobectomy.
Published: 2016

45. Bilobectomy for lung cancer: contemporary national early morbidity and ă mortality outcomes

Author: Thomas , Pascal A., Falcoz , Pierre-Emmanuel, Bernard , Alain, Le Pimpec-Barthes , Françoise, Jougon , Jacques, Brouchet , Laurent, Massard , Gilbert, Dahan , Marcel, Loundou , Anderson, Grp , EPITHOR, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, Service de chirurgie thoracique [AP-HP HEGP, Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), 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), CHU Toulouse [Toulouse], Unité d'Aide Méthodologique, Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-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) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes ( URMITE ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR48, INSB-INSB-Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche en Communications et en Cybernétique de Nantes ( IRCCyN ), Mines Nantes ( Mines Nantes ) -École Centrale de Nantes ( ECN ) -Ecole Polytechnique de l'Université de Nantes ( Polytech Nantes ), Université de Nantes ( UN ) -Université de Nantes ( UN ) -PRES Université Nantes Angers Le Mans ( UNAM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ), Institut des Maladies Métaboliques et Cardiovasculaires ( I2MC ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier ( UPS ), and Assistance Publique - Hôpitaux de Marseille ( APHM ) -CHU Marseille
Subjects: [ SHS.PSY ] Humanities and Social Sciences/Psychology, [ SDV.MHEP.PSM ] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [ SHS.ECO ] Humanities and Social Sciences/Economies and finances, [SHS.PSY]Humanities and Social Sciences/Psychology, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, Quality
Abstract: 23rd European Conference on General Thoracic Surgery, Lisbon, PORTUGAL, ă MAY 31-JUN 03, 2015; International audience; To determine contemporary early outcomes associated with bilobectomy for ă lung cancer and to identify their predictors using a nationally ă representative general thoracic surgery database. ă A total of 1831 patients, who underwent elective bilobectomy for primary ă lung cancer between 1 January 2004 and 31 December 2013, were selected. ă Logistic regression analysis was performed on variables for major ă adverse events. ă There were 670 upper and 1161 lower bilobectomies. Video-assisted ă thoracic surgery was seldom performed (2%). Induction therapy and ă extended resection were performed in 293 (16%) and 279 patients ă (15.2%), respectively. Operative mortality was 4.8% (upper: ă 4.5%/lower: 5%; P = 0.62), and significantly higher following extended ă procedures when compared with standard bilobectomy (4.3 vs 7.5%; P = ă 0.013). Pulmonary complication rate was 21.1%. Bronchial fistula ă occurred in 46 patients (2.5%) and pleural space complications in 296 ă (16.2%). Their respective incidence rates were significantly higher ă following lower than upper bilobectomy (3.5 vs 0.7%; P < 0.001 and 17.8 ă vs 13.3%; P = 0.007). At multivariate analysis, extended procedures ă [odds ratio (OR), 2.3; 95% confidence interval (CI), 1.03-5.31; P = ă 0.04], ASA scores of 3 or greater (OR, 2.02; 95% CI, 1.33-3.07; P < ă 0.001) and World Health Organization performance status 2 or greater ă (OR, 1.47; 95% CI, 1.01-2.13; P = 0.04) were risk predictors of ă mortality. Female gender (OR, 0.39; 95% CI, 0.19-0.80; P = 0.01), ă highest body mass index (BMI) values (OR, 0.91; 95% CI, 0.86-0.96; P = ă 0.001) and recent years of surgery (OR, 0.91; 95% CI, 0.84-0.99; P = ă 0.02) were protective. Predictors of bronchial fistula were male gender, ă lowest BMI values, lower bilobectomy and longest operative times. Male ă gender, lowest BMI values and longest operative times were also ă predictors of pulmonary complications, together with highest ASA scores ă and lowest forced expiratory volume in 1 s values. ă Risks related to lower bilobectomy lie halfway between those reported ă for lobectomy and pneumonectomy. Additional surgical measures to prevent ă pleural space complications and bronchial fistula should be encouraged ă with this operation. In contrast, upper bilobectomy shares more or less ă the same hazards as lobectomy.
Published: 2016

46. A Bayesian framework systematic review and meta-analysis of anesthetic ă agents effectiveness/tolerability profile in electroconvulsive therapy ă for major depression

Author: Laurent Boyer, Jean-Arthur Micoulaud-Franchi, Pascal Auquier, Pierre-Michel Llorca, Djamila Bennabi, Guillaume Fond, Emmanuel Haffen, Anderson Loundou, Christophe Lançon, Lore Brunel, Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] ( CAPS ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Sommeil, Attention et Neuropsychiatrie [Bordeaux] ( SANPSY ), Université de Bordeaux ( UB ) -CHU de Bordeaux Pellegrin [Bordeaux]-Centre National de la Recherche Scientifique ( CNRS ), Services d’explorations fonctionnelles du système nerveux, clinique du sommeil, CHU Bordeaux [Bordeaux], Unité d'Aide Méthodologique, Assistance Publique - Hôpitaux de Marseille ( APHM ) -CHU Marseille, Pôle de Psychiatrie 'Solaris', Service Pr. Naudin, Centre Hospitalier Universitaire de Sainte-Marguerite, Service de psychiatrie adulte - B, CHU Clermont-Ferrand, Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants ( SPMC ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ), Centre méditérannéen de médecine moléculaire ( C3M ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), INSERM U955, équipe 15, Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Réseau de coopération scientifique en santé mentale, Fondation FondaMental [Créteil]-Fondation FondaMental [Créteil]-Institut Mondor de Recherche Biomédicale ( IMRB ), Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10, Sommeil, Attention et Neuropsychiatrie [Bordeaux] (SANPSY), Université de Bordeaux (UB)-CHU de Bordeaux Pellegrin [Bordeaux]-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Département Universitaire de Psychiatrie - [Hôpital Sainte Marguerite - APHM] (Hôpitaux Sud), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants (SPMC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Réseau de coopération scientifique en santé mentale, Fondation FondaMental [Créteil]-Fondation FondaMental [Créteil]-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Sommeil, Addiction et Neuropsychiatrie [Bordeaux] (SANPSY), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre National de la Recherche Scientifique (CNRS)-CHU de Bordeaux Pellegrin [Bordeaux]-Université de Bordeaux (UB)
Subjects: medicine.medical_treatment, [ SDV.MHEP.PSM ] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SHS.PSY]Humanities and Social Sciences/Psychology, Article, 03 medical and health sciences, [ SHS.PSY ] Humanities and Social Sciences/Psychology, 0302 clinical medicine, Electroconvulsive therapy, Seizures, medicine, Humans, [ SHS.ECO ] Humanities and Social Sciences/Economies and finances, Ketamine, Electroconvulsive Therapy, Adverse effect, Depression (differential diagnoses), Anesthetics, Randomized Controlled Trials as Topic, Depressive Disorder, Major, Multidisciplinary, business.industry, Bayes Theorem, Electroencephalography, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, Quality, 030227 psychiatry, 3. Good health, Tolerability, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Methohexital, Anesthesia, Meta-analysis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Propofol, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: International audience; The aim of this study was to assess the efficacy and ă tolerability/acceptability of 6 anesthetic agents in ECT for depressive ă disorders. We systematically reviewed 14 double-blind randomized ă controlled trials (610 participants). Efficacy was measured by the mean ă scores on validated depression scales at 6 ECT (or the nearest score if ă not available), number of responders at the end of treatment and seizure ă duration. The acceptability was measured by the proportion of patients ă who dropped out of the allocated treatment, and the tolerability by the ă number of serious adverse events and post-treatment cognition ă assessment. After excluding the trials responsible for heterogeneity, ă depression scores of patients who were administered methohexital were ă found to be significantly more improved than those who received propofol ă (p = 0.001). On the contrary, those who were administered propofol had ă lower depression scores than those with thiopental at the end of ă treatment (p = 0.002). Compared to propofol, methohexital was found to ă be significantly associated with higher seizure duration (p = 0.018). No ă difference was found for the acceptability profile (all p > 0.05). In ă summary, ketamine and methohexital may be preferred to propofol or ă thiopental in regard of effectiveness in depression scores and increased ă seizure duration. Further studies are warranted to compare ketamine and ă methohexital.
Published: 2016

47. Age-related hearing loss in individuals and their caregivers: Effects of coping on the quality of life among the dyads

Author: Valérie Aghababian, Sébastien Lazzarotto, Anderson Loundou, Zeinab Hamidou, Tanguy Leroy, Pascal Auquier, Karine Baumstarck, Greps, Laboratoire, Aix Marseille Université (AMU), Unité d'Aide Méthodologique, Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants (SPMC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), 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), Groupe de Recherche en Psychologie Sociale (GRePS), Université Lumière - Lyon 2 (UL2), Aix Marseille Université ( AMU ), Assistance Publique - Hôpitaux de Marseille ( APHM ) -CHU Marseille, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants ( SPMC ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ), 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 )
Subjects: Gerontology, Coping (psychology), caregivers, Hearing loss, [ SDV.MHEP.PSM ] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, media_common.quotation_subject, Medicine (miscellaneous), [SHS.PSY]Humanities and Social Sciences/Psychology, Social psychology, [SHS.PSY] Humanities and Social Sciences/Psychology, [ SHS.PSY ] Humanities and Social Sciences/Psychology, 03 medical and health sciences, 0302 clinical medicine, Optimism, Quality of life, [ SHS.ECO ] Humanities and Social Sciences/Economies and finances, Medicine, 030223 otorhinolaryngology, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), age-related hearing impairment, ComputingMilieux_MISCELLANEOUS, media_common, Original Research, lcsh:R5-920, business.industry, Family caregivers, Health Policy, Avoidance coping, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, 3. Good health, coping, Mood, Patient Preference and Adherence, Health, 030220 oncology & carcinogenesis, dyads, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Quality of Life, Anxiety, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, emotional status, medicine.symptom, lcsh:Medicine (General), business, Social Sciences (miscellaneous)
Abstract: Sébastien Lazzarotto,1,2 Karine Baumstarck,1 Anderson Loundou,1 Zeinab Hamidou,1,3 Valérie Aghababian,1 Tanguy Leroy,1,4 Pascal Auquier1 1EA 3279, Self-Perceived Health Assessment Research Unit, School of Medicine, Aix Marseille Université, 2French Regional Institute for Prevention of Aging, Marseille, 3National Clinical Research Quality of Life in Oncology Platform, Marseille, 4Social Psychology Research Group (GRePS EA 4163), Université Lumière Lyon 2, Bron, France Objectives: Age-related hearing loss (ARHL) impacts the daily living and quality of life (QoL) of affected individuals and the functioning of family caregivers. In the specific context of voluntary medical checkups, we examined sample dyads (ARHL individual and the caregiver) to determine whether QoL of patients and caregivers is influenced by coping strategies implemented either by themselves or their relatives.Methods: This was a cross-sectional study with a descriptive/correlative design performed in a French preventive health center (Regional Institute for Prevention of Aging, Marseille, France) for the beneficiaries of pension funds of private sector employees. The samples included beneficiary–caregiver dyads. The beneficiaries had bilateral (mild to moderately severe) ARHL. Self-reported data were collected as follows: QoL using the World Health Organization Quality of Life questionnaire, coping strategies using the Brief Coping Orientation to Problems Experienced Scale, and anxiety and mood using visual analog scales.Results: The final sample comprised 44 beneficiaries and 44 caregivers. The caregiver was the partner of the beneficiary in 73% of cases. The QoL scores of the social dimension were significantly lower for beneficiaries and caregivers compared with French age- and sex-matched controls. Among beneficiaries and caregivers, coping strategies based on problem solving were the most commonly used strategies. The use of positive thinking strategies was associated with higher QoL scores. The more one member of the dyad used an avoidance coping strategy, the more the other member used a positive thinking strategy.Conclusion: This study emphasizes that QoL of individuals with age-related hearing impairment and their natural caregivers is related to the coping strategies that they use. This finding suggests that targeted interventions should be offered to help individuals who experience emotional difficulties to implement more efficient coping strategies. Keywords: age-related hearing impairment, caregivers, dyads, quality of life, coping, emotional status&nbsp
Published: 2016

48. Intra- and interobserver agreement among obstetric experts in court regarding the review of abnormal fetal heart rate tracings and obstetrical management

Author: Anderson Loundou, Xavier Carcopino, Florence Bretelle, Renaud Le Dû, Laura Sabiani, Claude D'Ercole, Léon Boubli, Santé Publique et maladies Chroniques : Qualité de vie Concepts, Usages et Limites, Déterminants (SPMC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), Unité d'Aide Méthodologique, Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Service d'Obstétrique-Gynécologie [Marseille], Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille- Hôpital Nord [CHU - APHM], Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Gynépole, Aix Marseille Université (AMU)- Hôpital Nord [CHU - APHM], Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), Service de gynécologie-obstétrique [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS), and INSB-INSB-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Clinical audit, Pediatrics, medicine.medical_specialty, Abnormal fetal heart rate, Cerebral palsy, Patient Admission, Pregnancy, Intensive Care Units, Neonatal, medicine, Humans, Partogram, Fetal Monitoring, Retrospective Studies, Observer Variation, Clinical Audit, business.industry, Obstetrics, Malpractice, Infant, Newborn, Obstetrics and Gynecology, Retrospective cohort study, Heart Rate, Fetal, Hydrogen-Ion Concentration, Middle Aged, Delivery, Obstetric, Fetal Blood, medicine.disease, Respiration, Artificial, Fetal heart rate, Apgar Score, Female, Apgar score, France, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, business
Abstract: International audience; OBJECTIVE: The objective of the study was to evaluate the intra-and interobserver agreement among obstetric experts in court regarding the retrospective review of abnormal fetal heart rate tracings and obstetrical management of patients with abnormal fetal heart rate during labor. STUDY DESIGN: A total of 22 French obstetric experts in court reviewed 30 cases of term deliveries of singleton pregnancies diagnosed with at least 1 hour of abnormal fetal heart rate, including 10 cases with adverse neonatal outcome. The experts reviewed all cases twice within a 3-month interval, with the first review being blinded to neonatal outcome. For each case reviewed, the experts were provided with the obstetric data and copies of the complete fetal heart rate recording and the partogram. The experts were asked to classify the abnormal fetal heart rate tracing and to express whether they agreed with the obstetrical management performed. When they disagreed, the experts were asked whether they concluded that an error had been made and whether they considered the obstetrical management as the cause of cerebral palsy in children if any. RESULTS: Compared with blinded review, the experts were significantly more likely to agree with the obstetric management performed (P \textless .001) and with the mode of delivery (P \textless .001) when informed about the neonatal outcome and were less likely to conclude that an error had been made (P \textless .001) or to establish a link with potential cerebral palsy (P = .003). The experts' intraobserver agreement for the review of abnormal fetal heart rate tracing and obstetrical management were both mediocre (kappa = 0.46-0.51 and kappa = 0.48-0.53, respectively). The interobserver agreement for the review of abnormal fetal heart rate tracing was low and was not improved by knowledge of the neonatal outcome (kappa = 0.11-0.18). The interobserver agreement for the interpretation of obstetrical management was also low (kappa = 0.08-0.19) but appeared to be improved by knowledge of the neonatal outcome (kappa = 0.15-0.32). CONCLUSION: The intra-and interobserver agreement among obstetric experts in court for the review of abnormal fetal heart rate tracing and the appropriateness of obstetrical care is poor, suggesting a lack of objectivity of obstetrical expertise as currently performed in court.
Published: 2015

49. First-line single-agent pembrolizumab for PD-L1-positive (tumor proportion score ≥ 50%) advanced non-small cell lung cancer in the real world: impact in brain metastasis: a national French multicentric cohort (ESCKEYP GFPC study)

Author: Renaud Descourt, Laurent Greillier, Maurice Perol, Charles Ricordel, Jean-Bernard Auliac, Lionel Falchero, Radj Gervais, Rémi Veillon, Sabine Vieillot, Florian Guisier, Marie Marcq, Grégoire Justeau, Laurence Bigay-Game, Marie Bernardi, Pierre Fournel, Hélène Doubre, Julian Pinsolle, Karim Amrane, Christos Chouaïd, Chantal Decroisette, Service d'Oncologie Thoracique (BREST - ICH), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Institut de cancérologie et hématologie, CHU Marseille, Aix Marseille Université (AMU), Hospices Civils de Lyon (HCL), Centre Léon Bérard [Lyon], Service de pneumologie [Rennes] = Pneumology [Rennes], CHU Pontchaillou [Rennes], CH, Mantes-La-Jolie, Centre Hospitalier de Villefranche sur Saône, Partenaires INRAE, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Bordeaux [Bordeaux], Catalan Institute of Oncology [Perpignan], Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Hôpital Foch [Suresnes], Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois]
Subjects: safety, Cancer Research, geriatric assessment, efficacy, MESH: Neoplasms, Glandular and Epithelial, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Guidelines, Thymic carcinoma, Non-small cell lung cancer, Chemotherapy, Immunology and Allergy, MESH: Cohort Studies, [STAT.AP]Statistics [stat]/Applications [stat.AP], Advanced stage, MESH: Humans, MESH: Thymoma, Radiotherapy, toxicity, Brain metastases, MESH: Retrospective Studies, Real-world study, MESH: Neoplasm Staging, targeted therapy, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, MESH: Prospective Studies, lung cancer, quality of life, Oncology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Surgery, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pembrolizumab, [PHYS.PHYS.PHYS-DATA-AN]Physics [physics]/Physics [physics]/Data Analysis, Statistics and Probability [physics.data-an], MESH: Thymus Neoplasms
Abstract: Few real-world data are available in patients with advanced metastatic non-small cell lung cancer (NSCLC) treated with first-line immunotherapy, particularly in those with brain metastases at treatment initiation.This was a national, retrospective, multicenter study that consecutively included all patients with PD-L1-positive (tumor proportion score ≥ 50%) advanced NSCLC who initiated first-line treatment with pembrolizumab as a single agent between May 2017 (date of availability of pembrolizumab in this indication in France) to November 22, 2019 (approval of the pembrolizumab-chemotherapy combination). Data were collected from medical records with local response assessment.The cohort included 845 patients and 176 (20.8%) had brain metastases at diagnosis. There were no significant differences in outcomes for patients with and without brain metastases: 9.2 (95% CI 5.6-15) and 8 (95% CI 6.7-9.2, p = 0.3) months for median progression-free survival (PFS) and, 29.5 (95% CI 17.2-NA) and 22 (95% CI 17.8-27.1, p = 0.3) months for median overall survival (OS), respectively. Overall response rates were 47% and 45% in patients with and without cerebral metastases. In multivariate analysis, performance status 2-4 vs. 0-1 and neutrophil-to-lymphocyte ratio ≥ 4 vs. 4 were the main independent negative factors for OS; brain metastasis was not an independent factor for OS.In this large multicenter cohort, nearly 20% of patients initiating pembrolizumab therapy for advanced NSCLC had cerebral metastases. There was no significant difference in response rates, PFS and OS between patients with and without brain metastases.
Published: 2022

50. Myocardial Revascularization Strategies in ST Elevation Myocardial Infarction Without Urgent Revascularization: Insight From a Nationwide Study

Author: Pierre Deharo, Alizée Porto, Thierry Bourguignon, Julien Herbert, Christophe Saint Etienne, Carl Semaan, Thibaud Genet, Nicolas Jaussaud, Pierre Morera, Alexis Theron, Vlad Gariboldi, Frederic Collart, Thomas Cuisset, Laurent Fauchier, Dysoxie, suractivité : aspects cellulaires et intégratifs thérapeutiques (DS-ACI / UMR MD2), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Département de Cardiologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital de la Timone [CHU - APHM] (TIMONE), Département de Chirurgie Cardiaque [Hôpital de la Timone - APHM], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Trousseau [Tours], CHU Marseille, 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), Éducation Éthique Santé EA 7505 (EES), and Université de Tours (UT)
Subjects: Stroke, Percutaneous Coronary Intervention, Treatment Outcome, Risk Factors, Myocardial Revascularization, Humans, ST Elevation Myocardial Infarction, Coronary Artery Disease, General Medicine, Coronary Artery Bypass, ComputingMilieux_MISCELLANEOUS, [SHS]Humanities and Social Sciences
Abstract: International audience; ObjectiveTo analyze the outcomes of patients presenting with ST-segment elevation myocardial infarction (STEMI) without early (
Published: 2022

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