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11,601 results on '"CHU Pitié Salpêtrière"'

1. Expression and Genetic Interaction of Transcription Factors GATA-2 and GATA-3 during Development of the Mouse Central Nervous System

Author: Nardelli, Jeannette, Thiesson, Danielle, Fujiwara, Yuko, Tsai, Fong-Ying, and Orkin, Stuart H.
Published: 1999
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2. Organization of the Articulatory System: Peripheral Mechanisms and Central Coordination

Author: Michèle Gentil and Chu Pitié-Salpêtrière
Subjects: Cerebellum, Speech production, Computer science, Speech recognition, Muscle spindle, Sensory system, Cerebellar lesions, Articulatory phonetics, Peripheral, Motor unit, medicine.anatomical_structure, otorhinolaryngologic diseases, medicine, Neuroscience
Abstract: The physiological mechanisms underlying oral communication are of primary interest. Investigations concerning the motor acts of speech are limited to what can be inferred from observation of the peripheral mechanisms of speech production. The neuromuscular events of speech movement patterning are described. In addition, speech movement coordination involves substantial adjustments among the multiple muscles of the various articulatory organs. The cerebellum is an important regulatory center for the control of motor activity. It provides smoothness to the contraction of synergist and antagonist muscles. It uses sensory information to predict, judge and correct the motor act. Damage to a structure with this capability would be expected to have consequences on speech production. The role of the cerebellum in speech control is examined by assessing the effects of cerebellar lesions on speech through a short review of literature.
Published: 1990
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3. Modifications of the endosomal compartment in fibroblasts from sporadic Alzheimer’s disease patients are associated with cognitive impairment

Author: Laura Xicota, Julien Lagarde, Fanny Eysert, Benjamin Grenier-Boley, Isabelle Rivals, Alexandra Botté, Sylvie Forlani, Sophie Landron, Clément Gautier, Cecilia Gabriel, Michel Bottlaender, Jean-Charles Lambert, Mounia Chami, Marie Sarazin, Marie-Claude Potier, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), GHU Paris Psychiatrie et Neurosciences, Université Paris Cité (UPCité), Université Paris-Saclay, Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS), Service Hospitalier Frédéric Joliot (SHFJ), 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 National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA), Institut de pharmacologie moléculaire et cellulaire (IPMC), 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), Université de Lille, CHU Lille, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Recherches SERVIER (IRS), Service NEUROSPIN (NEUROSPIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Xicota, Laura
Subjects: [SDV] Life Sciences [q-bio], Cellular and Molecular Neuroscience, Psychiatry and Mental health, [SDV]Life Sciences [q-bio], Biological Psychiatry
Abstract: Morphological alterations of the endosomal compartment have been widely described in post-mortem brains from Alzheimer’s disease (AD) patients and subjects with Down syndrome (DS) who are at high risk for AD. Immunostaining with antibodies against endosomal markers such as Early Endosome Antigen 1 (EEA1) revealed increased size of EEA1-positive puncta. In DS, peripheral cells such as peripheral blood mononuclear cells (PBMCs) and fibroblasts, share similar phenotype even in the absence of AD. We previously found that PBMCs from AD patients have larger EEA1-positive puncta, correlating with brain amyloid load. Here we analysed the endosomal compartment of fibroblasts from a very well characterised cohort of AD patients (IMABio3) who underwent thorough clinical, imaging and biomarkers assessments. Twenty-one subjects were included (7 AD with mild cognitive impairment (AD-MCI), 7 AD with dementia (AD-D) and 7 controls) who had amyloid-PET at baseline (PiB) and neuropsychological tests at baseline and close to skin biopsy. Fibroblasts isolated from skin biopsies were immunostained with anti-EEA1 antibody and imaged using a spinning disk microscope. Endosomal compartment ultrastructure was also analysed by electron microscopy. All fibroblast lines were genotyped and their AD risk factors identified. Our results show a trend to an increased EEA1-positive puncta volume in fibroblasts from AD-D as compared to controls (p.adj = 0.12) and reveal enhanced endosome area in fibroblasts from AD-MCI and AD-AD versus controls. Larger puncta size correlated with PiB retention in different brain areas and with worse cognitive scores at the time of biopsy as well as faster decline from baseline to the time of biopsy. Finally, we identified three genetic risk factors for AD (ABCA1, COX7C and MYO15A) that were associated with larger EEA1 puncta volume. In conclusion, the endosomal compartment in fibroblasts could be used as cellular peripheral biomarker for both amyloid deposition and cognitive decline in AD patients.
Published: 2023
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4. PTPA variants and impaired PP2A activity in early-onset parkinsonism with intellectual disability

Author: Fevga, Christina, Tesson, Christelle, Carreras Mascaro, Ana, Courtin, Thomas, Van Coller, Riaan, Sakka, Salma, Ferraro, Federico, Farhat, Nouha, Bardien, Soraya, Damak, Mariem, Carr, Jonathan, Ferrien, Melanie, Boumeester, Valerie, Hundscheid, Jasmijn, Grillenzoni, Nicola, Kessissoglou, Irini A., Kuipers, Demy J.S., Quadri, Marialuisa, Agid, Yves, Anheim, Mathieu, Borg, Michel, Brice, Alexis, Broussolle, Emmanuel, Corvol, Jean Christophe, Damier, Philippe, Defebvre, Luc, Dürr, Alexandra, Durif, Franck, Houeto, Jean Luc, Krack, Paul, Klebe, Stephan, Lesage, Suzanne, Lohmann, Ebba, Martinez, Maria, Mangone, Graziella, Mariani, Louise Laure, Pollak, Pierre, Rascol, Olivier, Tison, François, Tranchant, Christine, Verin, Marc, Viallet, François, Vidailhet, Marie, Emre, Murat, Hanagasi, Hasmet, Bilgic, Basar, Lu, Bedia Marangozog, Benmahdjoub, Mustapha, Arezki, Mohammed, Bouchetara, Sofiane A., Benhassine, Traki, Tazir, Meriem, Djebara, Mouna Ben, Gouider, Riadh, Romdhan, Sawssan Ben, Mhiri, Chokri, Bouhouche, Ahmed, Bonifati, Vincenzo, Mandemakers, Wim, Kievit, Anneke J.A., Boon, Agnita J.W., Ferreira, Joaquim J., Guedes, Leonor Correia, Hanagasi, Hasmet A., Tufekcioglu, Zeynep, Elibol, Bulent, Dog.u, Okan, Gultekin, Murat, Chien, Hsin F., Barbosa, Egberto, Jardim, Laura Bannach, Rieder, Carlos R.M., Chang, Hsiu Chen, Lu, Chin Song, Wu-Chou, Yah Huei, Yeh, Tu Hsueh, Lopiano, Leonardo, Tassorelli, Cristina, Pacchetti, Claudio, Comi, Cristoforo, Raudino, Francesco, Bertolasi, Laura, Tinazzi, Michele, Bonizzato, Alberto, Ferracci, Carlo, Marconi, Roberto, Guidi, Marco, Onofrj, Marco, Thomas, Astrid, Vanacore, Nicola, Meco, Giuseppe, Fabrizio, Edito, Fabbrini, Giovanni, Berardelli, Alfredo, Stocchi, Fabrizio, Vacca, Laura, Barone, Paolo, Picillo, Marina, De Michele, Giuseppe, Criscuolo, Chiara, De Mari, Michele, Dell'aquila, Claudia, Iliceto, Giovanni, Toni, Vincenzo, Trianni, Giorgio, Saddi, Valeria, Cossu, Gianni, Melis, Maurizio, Hassan, Bassem A., Breedveld, Guido J., Erasmus University Medical Center [Rotterdam] (Erasmus MC), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Faculty of Health Sciences [Pretoria], University of Pretoria [South Africa], Hopital Habib Bourguiba - Habib Bourguiba Hospital [Sfax], Stellenbosch University, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Motivation, cerveau et comportement = Motivation, Brain and Behavior [ICM Paris] (MBB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Tesson, Christelle, Clinical Genetics, and Neurology
Subjects: [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, intellectual disability, PTPA, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], PPP2R4, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, parkinsonism, PP2A
Abstract: The protein phosphatase 2A complex (PP2A), the major Ser/Thr phosphatase in the brain, is involved in a number of signalling pathways and functions, including the regulation of crucial proteins for neurodegeneration, such as alpha-synuclein, tau and LRRK2. Here, we report the identification of variants in the PTPA/PPP2R4 gene, encoding a major PP2A activator, in two families with early-onset parkinsonism and intellectual disability. We carried out clinical studies and genetic analyses, including genome-wide linkage analysis, whole-exome sequencing, and Sanger sequencing of candidate variants. We next performed functional studies on the disease-associated variants in cultured cells and knock-down of ptpa in Drosophila melanogaster. We first identified a homozygous PTPA variant, c.893T>G (p.Met298Arg), in patients from a South African family with early-onset parkinsonism and intellectual disability. Screening of a large series of additional families yielded a second homozygous variant, c.512C>A (p.Ala171Asp), in a Libyan family with a similar phenotype. Both variants co-segregate with disease in the respective families. The affected subjects display juvenile-onset parkinsonism and intellectual disability. The motor symptoms were responsive to treatment with levodopa and deep brain stimulation of the subthalamic nucleus. In overexpression studies, both the PTPA p.Ala171Asp and p.Met298Arg variants were associated with decreased PTPA RNA stability and decreased PTPA protein levels; the p.Ala171Asp variant additionally displayed decreased PTPA protein stability. Crucially, expression of both variants was associated with decreased PP2A complex levels and impaired PP2A phosphatase activation. PTPA orthologue knock-down in Drosophila neurons induced a significant impairment of locomotion in the climbing test. This defect was age-dependent and fully reversed by L-DOPA treatment. We conclude that bi-allelic missense PTPA variants associated with impaired activation of the PP2A phosphatase cause autosomal recessive early-onset parkinsonism with intellectual disability. Our findings might also provide new insights for understanding the role of the PP2A complex in the pathogenesis of more common forms of neurodegeneration.
Published: 2023
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5. Early identification of seizure freedom with medical treatment in patients with mesial temporal lobe epilepsy and hippocampal sclerosis

Author: Margaux Cheval, Marion Houot, Nathalie Chastan, William Szurhaj, Cécile Marchal, Hélène Catenoix, Luc Valton, Martine Gavaret, Bastien Herlin, Arnaud Biraben, Stanislas Lagarde, Laure Mazzola, Lorella Minotti, Louis Maillard, Sophie Dupont, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), 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), CHU Amiens-Picardie, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (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), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and None
Subjects: Neurology, Hippocampal sclerosis, Medically treated, Mesial temporal lobe epilepsy, Neurology (clinical), Machine-learning, Predictive factors, Seizure freedom, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is usually associated with a poor response to antiseizure medications. We focused on MTLE-HS patients who were seizure free on medication to: (1) determine the clinical factors associated with seizure freedom and (2) develop a machine-learning classifier to better earlier identify those patients.Methods: We performed a retrospective, multicentric study comparing 64 medically treated seizure-free MTLE-HS patients with 200 surgically treated drug-resistant MTLE-HS patients. First, we collected medical history and seizure semiology data. Then, we developed a machine-learning classifier based on clinical data.Results: Medically treated seizure-free MTLE-HS patients were seizure-free for at least 2 years, and for a median time of 7 years at last follow-up. Compared to drug-resistant MTLE-HS patients, they exhibited: an older age at epilepsy onset (22.5 vs 8.0 years, p < 0.001), a lesser rate of: febrile seizures (39.0% vs 57.5%, p = 0.035), focal aware seizures (previously referred to as aura)(56.7% vs 90.0%, p < 0.001), autonomic focal aware seizures in presence of focal aware seizure (17.6% vs 59.4%, p < 0.001), dystonic posturing of the limbs (9.8% vs 47.0%, p < 0.001), gestural (27.4% vs 94.0%, p < 0.001), oro-alimentary (32.3% vs 75.5%, p < 0.001) or verbal automatisms (12.9% vs 36.0%, p = 0.001). The classifier had a positive predictive value of 0.889, a sensitivity of 0.727, a specificity of 0.962, a negative predictive value of 0.893.Conclusions: Medically treated seizure-free MTLE-HS patients exhibit a distinct clinical profile. A classifier built with readily available clinical data can identify them accurately with excellent positive predictive value. This may help to individualize the management of MTLE-HS patients according to their expected pharmacosensitivity.
Published: 2023
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6. Rapid ventricular tachycardia in patients with tetralogy of Fallot and implantable cardioverter-defibrillator: Insights from the DAI-T4F nationwide registry

Author: Mikael Laredo, Guillaume Duthoit, Frédéric Sacher, Frédéric Anselme, Caroline Audinet, Francis Bessière, Pierre Bordachar, Abdeslam Bouzeman, Serge Boveda, Sok Sithikun Bun, Morgane Chassignolle, Gaël Clerici, Antoine Da Costa, Maxime de Guillebon, Pascal Defaye, Nathalie Elbaz, Romain Eschalier, Fabrice Extramiana, Laurent Fauchier, Alexis Hermida, Estelle Gandjbakhch, Rodrigue Garcia, Jean-Baptiste Gourraud, Charles Guenancia, Benoit Guy-Moyat, Didier Irles, Laurence Iserin, François Jourda, Linda Koutbi, Fabien Labombarda, Magalie Ladouceur, Philippe Lagrange, Nicolas Lellouche, Jacques Mansourati, Christelle Marquié, Raphael Martins, Grégoire Massoulié, Amel Mathiron, Philippe Maury, Anne Messali, Antoine Milhem, Pierre Mondoly, Cédric Nguyen, Sandro Ninni, Jean Luc Pasquié, Bertrand Pierre, Penelope Pujadas, Jean-Marc Sellal, Jean-Benoit Thambo, Camille Walton, Pierre Winum, Cyril Zakine, Alexandre Zhao, Xavier Jouven, Nicolas Combes, Eloi Marijon, Victor Waldmann, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Institut de rythmologie et modélisation cardiaque [Pessac] (IHU Liryc), 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), 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], CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
Subjects: Sudden cardiac death, Rapid ventricular tachycardia, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Physiology (medical), Tetralogy of Fallot, Ventricular arrhythmia, Adult congenital heart disease, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Cardiology and Cardiovascular Medicine, Implantable cardioverter-defibrillator
Abstract: In repaired tetralogy of Fallot (TOF), little is known about characteristics of patients with rapid ventricular tachycardia (VT). Also, whether patients with a first episode of nonrapid VT may subsequently develop rapid VT or ventricular fibrillation (VF) has not been addressed.The objectives of this study were to compare patients with rapid VT/VF with those with nonrapid VT and to assess the evolution of VT cycle lengths (VTCLs) overtime.Data were analyzed from a nationwide registry including all patients with TOF and implantable cardioverter-defibrillator (ICD) since 2000. Patients with ≥1 VT episode with VTCL ≤250 ms (240 beats/min) formed the rapid VT/VF group.Of 144 patients (mean age 42.0 ± 12.7 years; 104 [72%] men), 61 (42%) had at least 1 VT/VF episode, including 28 patients with rapid VT/VF (46%), during a median follow-up of 6.3 years (interquartile range 2.2-10.3 years). Compared with patients in the nonrapid VT group, those in the rapid VT/VF group were significantly younger at ICD implantation (35.2 ± 12.6 years vs 41.5 ± 11.2 years; P = .04), had more frequently a history of cardiac arrest (8 [29%] vs 2 [6%]; P = .02), less frequently a history of atrial arrhythmia (11 [42%] vs 22 [69%]; P = .004), and higher right ventricular ejection fraction (43.3% ± 10.3% vs 36.6% ± 11.2%; P = .04). The median VTCL of VT/VF episodes was 325 ms (interquartile range 235-429 ms). None of the patients with a first documented nonrapid VT episode had rapid VT/VF during follow-up.Patients with TOF and rapid VT/VF had distinct clinical characteristics. The relatively low variation of VTCL over time suggests a room for catheter ablation without a backup ICD in selected patients with well-tolerated VT.Clinicaltrials.gov identifier: NCT03837574.
Published: 2023
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7. 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
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8. Molecular and clinical diversity in primary central nervous system lymphoma

Author: Hernández-Verdin, I., Kirasic, E., Wienand, K., Mokhtari, K., Eimer, S., Loiseau, H., Rousseau, A., Paillassa, J., Ahle, G., Lerintiu, F., Uro-Coste, E., Oberic, L., Figarella-Branger, D., Chinot, O., Gauchotte, G., Taillandier, L., Marolleau, J.-P., Polivka, M., Adam, C., Ursu, R., Schmitt, A., Barillot, N., Nichelli, L., Lozano-Sánchez, F., Ibañez-Juliá, M.-J., Peyre, M., Mathon, B., Abada, Y., Charlotte, F., Davi, F., Stewart, C., de Reyniès, A., Choquet, S., Soussain, C., Houillier, C., Chapuy, B., Hoang-Xuan, K., Alentorn, A., 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), University Medical Center Göttingen (UMG), Freie Universität Berlin, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, CHU Bordeaux [Bordeaux], Imagerie moléculaire et thérapies innovantes en oncologie (IMOTION), Université de Bordeaux (UB), Centre de Recherche en Cancérologie et 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)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Hôpitaux Civils de Colmar, Centre de Recherches en Cancérologie de Toulouse (CRCT), 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), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), 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), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris Diderot - Paris 7 (UPD7), Hopital Saint-Louis [AP-HP] (AP-HP), Institut Bergonié [Bordeaux], UNICANCER, Sorbonne Université (SU), Centre Hospitalier Saint Jean de Perpignan, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Institut Curie - Saint Cloud (ICSC), DESSAIVRE, Louise, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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), 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 d’Anatomie Pathologique [CHRU Nancy], and École pratique des hautes études (EPHE)
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Oncology, tumor heterogeneity, Hematology, multi-omics, microenvironment, PCNSL, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Primary central nervous system lymphoma (PCNSL) is a rare and distinct entity within diffuse large B-cell lymphoma presenting with variable response rates probably to underlying molecular heterogeneity.To identify and characterize PCNSL heterogeneity and facilitate clinical translation, we carried out a comprehensive multi-omic analysis [whole-exome sequencing, RNA sequencing (RNA-seq), methylation sequencing, and clinical features] in a discovery cohort of 147 fresh-frozen (FF) immunocompetent PCNSLs and a validation cohort of formalin-fixed, paraffin-embedded (FFPE) 93 PCNSLs with RNA-seq and clinico-radiological data.Consensus clustering of multi-omic data uncovered concordant classification of four robust, non-overlapping, prognostically significant clusters (CS). The CS1 and CS2 groups presented an immune-cold hypermethylated profile but a distinct clinical behavior. The 'immune-hot' CS4 group, enriched with mutations increasing the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and nuclear factor-κB activity, had the most favorable clinical outcome, while the heterogeneous-immune CS3 group had the worse prognosis probably due to its association with meningeal infiltration and enriched HIST1H1E mutations. CS1 was characterized by high Polycomb repressive complex 2 activity and CDKN2A/B loss leading to higher proliferation activity. Integrated analysis on proposed targets suggests potential use of immune checkpoint inhibitors/JAK1 inhibitors for CS4, cyclin D-Cdk4,6 plus phosphoinositide 3-kinase (PI3K) inhibitors for CS1, lenalidomide/demethylating drugs for CS2, and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibitors for CS3. We developed an algorithm to identify the PCNSL subtypes using RNA-seq data from either FFPE or FF tissue.The integration of genome-wide data from multi-omic data revealed four molecular patterns in PCNSL with a distinctive prognostic impact that provides a basis for future clinical stratification and subtype-based targeted interventions.
Published: 2023
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9. Neurodevelopmental disorders (NDD) without boundaries: research and interventions beyond classifications

Author: Cécile Louveau, Pierre Ellul, Anton Iftimovici, Julien Dubreucq, Charles Laidi, Quentin Leyrolle, Diane Purper-Ouakil, Sebastien Jacquemont, Stanislas Lyonnet, Catherine Barthélémy, Marie-Odile Krebs, Jing Bai, Paul Olivier, Boris Chaumette, GHU Paris Psychiatrie et Neurosciences, AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (CNC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Etienne, Child Mind Institute, Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Hôpital Saint Eloi (CHRU Montpellier), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), CHU Necker - Enfants Malades [AP-HP], GIS autisme et troubles du neuro-développement (GIS-Autisme et TND), Université de Tours (UT), McGill University = Université McGill [Montréal, Canada], Martinez Rico, Clara, Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (ISC-MJ), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Psychiatry and Mental health, Neurology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Biological Psychiatry
Abstract: International audience; On June 2022, the 2nd Webinar "Neurodevelopmental Disorders (NDD) without boundaries took place at the Imagine Institute in Paris and was broadcasted live and in replay. The aim of this webinar is to address NDD in a dimensional rather than in a categorical approach. Several speakers were invited to present their researches on the subject. Classifications in NDD were discussed: irritability in NDD, involvement of the immune system in neurodevelopment, nutrition and gut microbiota modulate brain inflammation and neurodevelopment, co-occurring conditions in autistic adolescents and adults without intellectual disability. Classifications in psychiatric disorders were asked: mapping the effect of genes on cognition and autism risk, epigenetics and symptomatic trajectory in neurodevelopmental disorders, the autism-schizophrenia continuum in two examples: minor neurological signs and EEG microstates, the cerebellum in schizophrenia and autism: from imaging to intervention perspectives. Both genetic and environmental factors, along with clinical and imaging features, argue toward a continnum between NDD but also with adult psychiatric presentations. This new paradigm could modify the therapeutic strategy, with the development of large-spectrum treatments or new psychotherapies addressing co-occuring symptoms. The complexity and the heterogeneity of NDD apply well to the next scientific and political challenges: developing international convergence to push back the frontiers of our knowledge. This article is a summary of the 2nd webinar "Neurodevelopmental Disorders (NDD) without boundaries: research and interventions beyond classifications" sponsored by the French National Academy of Medicine, the autism and neurodevelopmental disorders scientific interest group (GIS), the International Research Network Dev-O-Psy and the French Institute of Psychiatry (GDR3557). Oral presentations are available as a replay on the following website (in French): https://autisme-neurodev.org/evenements/2022/04/12/tnd-sans-frontieres-la-recherche-et-les-interventions-au-dela-des-classifications/ .
Published: 2023
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10. Diagnosis and management of adult primary angiitis of the central nervous system: an international survey on current practices

Author: Ahmad Nehme, Sylvain Lanthier, Marion Boulanger, Achille Aouba, Patrice Cacoub, David Jayne, Jean-Paul Makhzoum, Christian Pagnoux, Maxime Rhéaume, Benjamin Terrier, Emmanuel Touzé, Hubert de Boysson, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital du Sacré-Coeur de Montréal, Université de Montréal (UdeM), Normandie Université (NU), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), University of Cambridge [UK] (CAM), University of Toronto, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and CACOUB, Patrice
Subjects: Practice, Primary angiitis of the central nervous system, [SDV.IMM] Life Sciences [q-bio]/Immunology, Neurology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Neurology (clinical), Survey, Central nervous system vasculitis, Management
Abstract: International audience; Background: Primary angiitis of the central nervous system (PACNS) is a rare disease, for which no validated guidelines exist. We report the findings of a survey on the clinical practice of physicians who manage adults with PACNS.Methods: An online survey was distributed through neurology, internal medicine, and rheumatology societies in Canada and Europe. Participants who were directly involved as treating physicians for at least two adult patients with PACNS were eligible for the survey.Results: Ninety-six physicians completed the survey. Most participants were neurologists (n = 38, 40%), internists (n = 34, 35%) or rheumatologists (n = 22, 23%). Participants obtained a CNS biopsy in a median of 25% (IQR: 5-50%) of suspected PACNS cases. When determining the degree to which eight scenarios justified a CNS biopsy, participants achieved fair inter-rater agreement (Gwet's AC2 0.30, 95% CI 0.23-0.41). For induction therapy, 81 (84%) participants reported using glucocorticoids and cyclophosphamide in > 50% of patients. After obtaining remission, 85 (89%) participants systematically introduced or maintained immunosuppressive therapy. Glucocorticoids were prescribed for a median of 12 months. Maintenance therapy with another immunosuppressant was continued for a median of 24 months. In patients who achieved remission, we explored how eight scenarios with different imaging and CSF results supported an increase in treatment. Inter-rater agreement was substantial if the patient was symptomatic (0.66, 95% CI 0.58-0.80) and moderate (0.50, 95% CI 0.45-0.60) if asymptomatic.Conclusion: This survey illustrates current real-world management of PACNS and emphasizes several areas for which physicians still lack study-based evidence and/or clinical practice guidelines.
Published: 2022
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11. Disease Progression Score Estimation From Multimodal Imaging and MicroRNA Data Using Supervised Variational Autoencoders

Author: Virgilio Kmetzsch, Emmanuelle Becker, Dario Saracino, Daisy Rinaldi, Agnes Camuzat, Isabelle Le Ber, Olivier Colliot, Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Dynamics, Logics and Inference for biological Systems and Sequences (Dyliss), Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-GESTION DES DONNÉES ET DE LA CONNAISSANCE (IRISA-D7), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), The research leading to these results has received funding from the French government under management of Agence Nationale de la Recherche, references ANR-19-P3IA-0001 (PRAIRIE 3IA Institute), ANR-10-IAIHU-06, project PREV-DEMALS (grant number ANR-14-CE15-0016-07), and from the Inria Project Lab Program (project Neuromarkers)., ANR-19-P3IA-0001,PRAIRIE,PaRis Artificial Intelligence Research InstitutE(2019), ANR-14-CE15-0016,PREV-DEMALS,Prédire pour prévenir les démences frontotemporales (DFT) et la sclérose latérale amyotrophique (SLA)(2014), Colliot, Olivier, PaRis Artificial Intelligence Research InstitutE - - PRAIRIE2019 - ANR-19-P3IA-0001 - P3IA - VALID, and Appel à projets générique - Prédire pour prévenir les démences frontotemporales (DFT) et la sclérose latérale amyotrophique (SLA) - - PREV-DEMALS2014 - ANR-14-CE15-0016 - Appel à projets générique - VALID
Subjects: [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], Deep learning, MicroRNA, Neuroimaging, Health Informatics, Variational autoencoder, Neurodegenerative disease, Disease progression score, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], Computer Science Applications, [INFO.INFO-CV] Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Multimodal data, [INFO.INFO-TI] Computer Science [cs]/Image Processing [eess.IV], Health Information Management, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Electrical and Electronic Engineering, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, [SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing
Abstract: International audience; Frontotemporal dementia and amyotrophic lateral sclerosis are rare neurodegenerative diseases with no effective treatment. The development of biomarkers allowing an accurate assessment of disease progression is crucial for evaluating new therapies. Concretely, neuroimaging and transcriptomic (microRNA) data have been shown useful in tracking their progression. However, no single biomarker can accurately measure progression in these complex diseases. Additionally, large samples are not available for such rare disorders. It is thus essential to develop methods that can model disease progression by combining multiple biomarkers from small samples. In this paper, we propose a new framework for computing a disease progression score (DPS) from cross-sectional multimodal data. Specifically, we introduce a supervised multimodal variational autoencoder that can infer a meaningful latent space, where latent representations are placed along a disease trajectory. A score is computed by orthogonal projections onto this path. We evaluate our framework with multiple synthetic datasets and with a real dataset containing 14 patients, 40 presymptomatic genetic mutation carriers and 37 controls from the PREV-DEMALS study. There is no ground truth for the DPS in real-world scenarios, therefore we use the area under the ROC curve (AUC) as a proxy metric. Results with the synthetic datasets support this choice, since the higher the AUC, the more accurate the predicted simulated DPS. Experiments with the real dataset demonstrate better performance in comparison with stateof-the-art approaches. The proposed framework thus leverages cross-sectional multimodal datasets with small sample sizes to objectively measure disease progression, with potential application in clinical trials.
Published: 2022
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12. 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
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13. Impact of Prone Position in COVID-19 Patients on Extracorporeal Membrane Oxygenation*

Author: Massart, Nicolas, Guervilly, Christophe, Mansour, Alexandre, Porto, Alizée, Flécher, Erwan, Esvan, Maxime, Fougerou, Claire, Fillâtre, Pierre, Duburcq, Thibault, Lebreton, Guillaume, Para, Marylou, Stephan, François, Hraiech, Sami, Ross, James, Schmidt, Matthieu, Vincentelli, André, Nesseler, Nicolas, CHU Pontchaillou [Rennes], Hôpital Yves LE FOLL [Saint-Brieuc], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Hôpital Nord [CHU - APHM], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Lille, Université de Lille, 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), 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, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Marie-Lannelongue, University of California [Davis] (UC Davis), University of California (UC), 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), Extracorporeal Membrane Oxygenation for Respiratory Failure and/or Heart failure related to Severe Acute Respiratory Syndrome Coronavirus 2 (ECMOSARS) Investigators: Olivier Fouquet, Marc Pierrot, Sidney Chocron, Guillaume Flicoteaux, Philippe Mauriat, Hadrien Roze, Alexandre Ouattara, Olivier Huet, Marc-Olivier Fischer, Claire Alessandri, Raphel Bellaïche, Ophélie Constant, Quentin De Roux, André Ly, Arnaud Meffert, Jean-Claude Merle, Lucile Picard, Elena Skripkina, Thierry Folliguet, Nicolas Mongardon, Antonio Fiore, Nicolas D'ostrevy, Marie-Catherine Morgan, Maxime Nguyen, Pierre-Grégoire Guinot, Lucie Gaide-Chevronnay, Nicolas Terzi, Gwenhaël Colin, Olivier Fabre, Arash Astaneh, Justin Issard, Elie Fadel, Dominique Fabre, Antoine Girault, Iolande Ion, Jean Baptiste Menager, Delphine Mitilian, Julien Guihaire, Olaf Mercier, Jacques Thes, Jerôme Jouan, Thibault Duburcq, Valentin Loobuyck, Sabrina Manganiello, Mouhammed Moussa, Agnes Mugnier, Natacha Rousse, Olivier Desebbe, Roland Henaine, Matteo Pozzi, Jean-Luc Fellahi, Jean-Christophe Richard, Zakaria Riad, Laurent Papazian, Matthias Castanier, Charles Chanavaz, Cyril Cadoz, Sebastien Gette, Guillaume Louis, Erick Portocarrero, Philippe Gaudard, Kais Brini, Nicolas Bischoff, Antoine Kimmoun, Bruno Levy, Mathieu Mattei, Pierre Perez, Alexandre Bourdiol, Yannick Hourmant, Pierre-Joachim Mahé, Bertrand Rozec, Mickaël Vourc'h, Stéphane Aubert, Florian Bazalgette, Claire Roger, Sophie Provenchere, Pierre Jaquet, Brice Lortat-Jacob, Pierre Mordant, Patrick Nataf, Juliette Patrier, Morgan Roué, Romain Sonneville, Alexy Tran-Dinh, Paul-Henri Wicky, Charles Al Zreibi, Bernard Cholley, Yannis Guyonvarch, Sophie Hamada, Claudio Barbanti, Anatole Harrois, Astrid Bertier, Jordi Matiello, Thomas Kerforne, Corentin Lacroix, Nicolas Brechot, Juliette Chommeloux, Alain Combes, Jean Michel Constantin, Cosimo D'alessandro, Pierre Demondion, Alexandre Demoule, Martin Dres, Muriel Fartoukh, Guillaume Hekimian, Charles Juvin, Pascal Leprince, Guillaume Fadel, David Levy, Charles Edouard Luyt, Marc Pineton de Chambrun, Thibaut Schoell, Roxane Nicolas, Maud Jonas, Charles Vidal, Nicolas Allou, Salvatore Muccio, Dario Di Perna, Bruno Mourvillier, Vito-Giovanni Ruggieri, Amedeo Anselmi, Karl Bounader, Yoann Launey, Thomas Lebouvier, Alessandro Parasido, Florian Reizine, Philippe Seguin, Emmanuel Besnier, Dorothée Carpentier, Thomas Clavier, Anne Olland, Pierre-Emmanuel Falcoz, Marion Villard, Fanny Bounes, François Labaste, Vincent Minville, Antoine Guillon, Yannick Fedun, and MORNET, Dominique
Subjects: [SDV] Life Sciences [q-bio], critical care, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV]Life Sciences [q-bio], prone position, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, acute respiratory distress syndrome, extracorporeal membrane oxygenation, mechanical ventilation, Critical Care and Intensive Care Medicine, mortality
Abstract: International audience; Objectives: Prone positioning and venovenous extracorporeal membrane oxygenation (ECMO) are both useful interventions in acute respiratory distress syndrome (ARDS). Combining the two therapies is feasible and safe, but the effectiveness is not known. Our objective was to evaluate the potential survival benefit of prone positioning in venovenous ECMO patients cannulated for COVID-19-related ARDS.Design: Retrospective analysis of a multicenter cohort.Patients: Patients on venovenous ECMO who tested positive for severe acute respiratory syndrome coronavirus 2 by reverse transcriptase polymerase chain reaction or with a diagnosis on chest CT were eligible.Interventions: None.Measurements and main results: All patients on venovenous ECMO for respiratory failure in whom prone position status while on ECMO and in-hospital mortality were known were included. Of 647 patients in 41 centers, 517 were included. Median age was 55 (47-61), 78% were male and 95% were proned before cannulation. After cannulation, 364 patients (70%) were proned and 153 (30%) remained in the supine position for the whole ECMO run. There were 194 (53%) and 92 (60%) deaths in the prone and the supine groups, respectively. Prone position on ECMO was independently associated with lower in-hospital mortality (odds ratio = 0.49 [0.29-0.84]; p = 0.010). In 153 propensity score-matched pairs, mortality rate was 49.7% in the prone position group versus 60.1% in the supine position group (p = 0.085). Considering only patients alive at decannulation, propensity-matched proned patients had a significantly lower mortality rate (22.4% vs 37.8%; p = 0.029) than nonproned patients.Conclusions: Prone position may be beneficial in patients supported by venovenous ECMO for COVID-19-related ARDS but more data are needed to draw definitive conclusions.
Published: 2022
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14. SARS-CoV-2 infection in patients with primary central nervous system lymphoma in the vaccination era

Author: Alice Laurenge, Renata Ursu, Emeline Tabouret, Vincent Harlay, Guido Ahle, Sylvain Choquet, Carole Soussain, Cécile Moluçon-Chabrot, Bertrand Mathon, Karima Mokhtari, Valérie Pourcher, Lucia Nichelli, Stéphane Marot, Mehdi Touat, Khê Hoang-Xuan, Caroline Houillier, 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), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), CH Colmar, Institut Curie [Paris], Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: Cancer Research, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Oncology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Hematology
Published: 2022
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15. 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
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16. Annonaceae Consumption Worsens Disease Severity and Cognitive Deficits in Degenerative Parkinsonism

Author: Laurent Cleret de Langavant, Emmanuel Roze, Aimée Petit, Benoit Tressières, Amin Gharbi‐Meliani, Hugo Chaumont, Patrick Pierre Michel, Anne‐Catherine Bachoud‐Lévi, Philippe Remy, Régine Edragas, Annie Lannuzel, Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, IMRB - 'NeuroPsychologie Interventionnelle' [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), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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), CHU Pointe-à-Pitre/Abymes [Guadeloupe], Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], CHU de la Martinique [Fort de France], and Michel, Patrick Pierre
Subjects: [SDV] Life Sciences [q-bio], risk factor, Neurology, [SDV]Life Sciences [q-bio], food toxin, Annonaceae, Parkinson, Neurology (clinical), cognitive impairment
Abstract: International audience; Background: High consumption of Annona muricata fruit has been previously identified as a risk factor for atypical parkinsonism in the French Caribbean islands.Objective: We tested whether consumption of Annonaceae products could worsen the clinical phenotype of patients with any form of degenerative parkinsonism.Methods: We analyzed neurological data from 180 Caribbean parkinsonian patients and specifically looked for dose effects of lifelong, cumulative Annonaceae consumption on cognitive performance. Using unsupervised clustering, we identified one cluster with mild/moderate symptoms (N = 102) and one with severe symptoms including cognitive impairment (N = 78).Results: We showed that even low cumulative consumption of fruits/juices (>0.2 fruit-years) or any consumption of herbal tea from Annonaceae worsen disease severity and cognitive deficits in degenerative parkinsonism including Parkinson's disease (OR fruits-juices: 3.76 [95% CI: 1.13-15.18]; OR herbal tea: 2.91 [95% CI: 1.34-6.56]).Conclusion: We suggest that more restrictive public health preventive recommendations should be made regarding the consumption of Annonaceae products. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Published: 2022
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17. Sotrovimab to prevent severe COVID-19 in high-risk patients infected with Omicron BA.2

Author: Guillaume Martin-Blondel, Anne-Genevieve Marcelin, Cathia Soulié, Sofia Kaisaridi, Clovis Lusivika-Nzinga, Céline Dorival, Laura Nailler, Anaïs Boston, Cléa Melenotte, André Cabié, Christophe Choquet, François Coustillères, Jean-Philippe Martellosio, Géraldine Gaube, Albert Trinh-Duc, Anne-Marie Ronchetti, Valerie Pourcher, Marie Chauveau, Karine Lacombe, Nathan Peiffer-Smadja, Pierre Housset, Aurore Perrot, Gilles Pialoux, Aurélie Martin, Vincent Dubee, Mathilde Devaux, Jérôme Frey, Charles Cazanave, Roland Liblau, Fabrice Carrat, Youri Yordanov, Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), 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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), ANRS France Recherche Nord & sud Sida-hiv hépatites, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier]-Université de Montpellier (UM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Accueil des Urgences (AGEN - SAU), Centre Hospitalier d'Agen, Centre Hospitalier Sud Francilien, Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Hôtel-Dieu de 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), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Services de Maladies Infectieuses et Tropicales [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Maladies infectieuses et tropicales [CHU Tenon], CHU Tenon [AP-HP], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Médecine Interne [CHI Poissy-Saint-Germain], Centre Hospitalier Intercommunal de Poissy-Saint Germain-en-Laye (CHI Poissy-Saint Germain-en-Laye), CHR de Metz-Thionville, CHU Bordeaux [Bordeaux], Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Service d'Allergologie et d'Immunologie [CHU Toulouse], Épidémiologie clinique des maladies virales chroniques [iPLesp] (CLEPIVIR), 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), Service de santé publique [CHU Saint-Antoine], 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)-Sorbonne Université (SU), Service d'Urgences Adultes [CHU Saint-Antoine], and Gestionnaire, Hal Sorbonne Université
Subjects: [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Microbiology (medical), [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, COVID-19, Humans, Antibodies, Monoclonal, Humanized, Antibodies, Neutralizing
Abstract: International audience; Before the Omicron era, the neutralizing antibody targeting the SARS-CoV2 Spike protein Sotrovimab has been shown to reduce the risk of COVID-19-related hospitalization in patients who are at high risk for progression (1, 2). We recently showed that early administration of Sotrovimab in Omicron-infected patients with very high-risk for progression was associated with a low rate of COVID-19-related hospitalization within one month after treatment administration (3%), and with no death (1). However, the dominance of the Omicron sublineage BA.2 led health agencies to suspend Sotrovimab emergency use authorizations because of its lower neutralizing ability in vitro compared to BA.1 sublineage (3, 4). Clinical efficiency of Sotrovimab to prevent COVID-19 related complications in high-risk patients with mild-to-moderate COVID-19 Omicron BA.2 remains unknown. Our aim was to compare the clinical and virological outcomes of Omicron BA.1 and BA.2-infected patients with mild-to-moderate COVID-19 who received 500 mg of Sotrovimab IV to prevent COVID-19-related complications.
Published: 2022
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18. Immediate versus staged complete myocardial revascularization in patients with ST-segment elevation myocardial infarction and multivessel disease: A post hoc analysis of the randomized FLOWER-MI trial

Author: Victoria Tea, Jean-François Morelle, Romain Gallet, Guillaume Cayla, Gilles Lemesle, Thibault Lhermusier, Jean-Guillaume Dillinger, Grégory Ducrocq, Denis Angouvant, Yves Cottin, Chekrallah Chamandi, Alicia le Bras, Philippe Gabriel Steg, Gilles Montalescot, Anaïs Charles Nelson, Tabassome Simon, Gilles Chatellier, Nicolas Danchin, Etienne Puymirat, 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), Hôpital privé Saint-Martin - Ramsay Santé, Service de Cardiologie [Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, IMRB - 'Biologie du système neuromusculaire' [Créteil] (U955 Inserm - UPEC), École nationale vétérinaire - Alfort (ENVA)-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), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Alliance française pour les essais cliniques cardio-vasculaires - French Alliance for Cardiovascular Trials (FACT), Pole Cardio-vasculaire et pulmonaire [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD), 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), Université Toulouse III Paul Sabatier - Faculté de médecine Purpan (UTPS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT), Service Cardiologie [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Service de Chirurgie Thoracique et Vasculaire [Hôpital Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Physiopathologie et épidémiologie cérébro-cardiovasculaire [Dijon] (PEC2), Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Cardiologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupe Action, 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)-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), 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), CIC - HEGP (CIC 1418), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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), Unité de recherche Phytopharmacie et Médiateurs Chimiques (UPMC), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), and Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Fractional flow reserve, Multivessel disease, MESH: Humans, MESH: Percutaneous Coronary Intervention / methods, Acute myocardial infarction, Coronary Artery Disease, General Medicine, MESH: Myocardial Revascularization / methods, MESH: Fractional Flow Reserve, Myocardial, Fractional Flow Reserve, Myocardial, MESH: Coronary Artery Disease / surgery, Percutaneous Coronary Intervention, Treatment Outcome, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Myocardial Revascularization, Humans, ST Elevation Myocardial Infarction, MESH: Coronary Artery Disease / diagnostic imaging, MESH: ST Elevation Myocardial Infarction / diagnostic imaging, Cardiology and Cardiovascular Medicine, MESH: ST Elevation Myocardial Infarction / therapy, MESH: Treatment Outcome
Abstract: International audience; Background: in patients with ST-segment elevation myocardial infarction and multivessel disease, percutaneous coronary intervention for non-culprit lesions is superior to treatment of the culprit lesion alone. The optimal timing for non-infarct-related artery revascularization - immediate versus staged - has not been investigated adequately. Aim: we aimed to assess clinical outcomes at 1 year in patients with ST-segment elevation myocardial infarction with multivessel disease using immediate versus staged non-infarct-related artery revascularization. Methods: outcomes were analysed in patients from the randomized FLOWER-MI trial, in whom, after successful primary percutaneous coronary intervention, non-culprit lesions were assessed using fractional flow reserve or angiography during the index procedure or during a staged procedure during the initial hospital stay, ≤5 days after the index procedure. The primary outcome was a composite of all-cause death, non-fatal myocardial infarction and unplanned hospitalization with urgent revascularization at 1 year. Results: among 1171 patients enrolled in this study, 1119 (96.2%) had complete revascularization performed during a staged procedure, and 44 (3.8%) at the time of primary percutaneous coronary intervention. During follow-up, a primary outcome event occurred in one of the patients (2.3%) with an immediate strategy and in 55 patients (4.9%) with a staged strategy (adjusted hazard ratio 1.44, 95% confidence interval 0.39-12.69; P=0.64). Conclusions: staged non-infarct-related artery complete revascularization was the strategy preferred by investigators in practice in patients with ST-segment elevation myocardial infarction with multivessel disease. This strategy was not superior to immediate revascularization, which, in the context of this trial, was used in a small proportion of patients. Further randomized studies are needed to confirm these observational findings.
Published: 2022
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19. Stratifying sudden death risk in adults with drug‐resistant focal epilepsy: The <scp>SUDEP‐CARE</scp> score

Author: Chris Serrand, Sylvain Rheims, Marie Faucanié, Arielle Crespel, Vera Dinkelacker, William Szurhaj, Arnaud Biraben, Fabrice Bartolomei, Nathalie de Grissac, Elizabeth Landré, Marie Denuelle, Laurent Vercueil, Cécile Marchal, Louis Maillard, Philippe Derambure, Sophie Dupont, Vincent Navarro, Thibault Mura, Audrey Jaussent, Valérie Macioce, Philippe Ryvlin, Marie‐Christine Picot, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (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), Hôpital de Hautepierre [Strasbourg], Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Lille, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Sainte Anne [Paris], Centre de recherche cerveau et cognition (CERCO UMR5549), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire [Grenoble] (CHU), Domaine expérimental de Vassal (MONTP DOM VASSAL), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Montpellier (UM), Unité de Neurologie Fonctionnelle et d'Épileptologie, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut de Génomique Fonctionnelle (IGF), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: Sudden Death, Epilepsy, SUDEP, Neurology, Risk score, Neurology (clinical), case-control, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background and purpose - A clinical risk score for sudden unexpected death in epilepsy (SUDEP) in patients with drug-resistant focal epilepsy could help improve prevention. Methods - A case-control study was conducted including (i) definite or probable SUDEP cases collected by the French National Sentinel Mortality Epilepsy Network and (ii) control patients from the French national research database of epilepsy monitoring units. Patients with drug-resistant focal epilepsy were eligible. Multiple logistic regressions were performed. After sensitivity analysis and internal validation, a simplified risk score was developed from the selected variables. Results - Sixty-two SUDEP cases and 620 controls were included. Of 21 potential predictors explored, seven were ultimately selected, including generalized seizure frequency (>1/month vs.
Published: 2022
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20. Precision Medicine for Idiopathic Hypersomnia

Author: Pauline Dodet, Smaranda Leu-Semenescu, Isabelle Arnulf, Centre National de Référence pour les Maladies Rares : narcolepsie, hypersomnie idiopathique et syndrome de Kleine-Levin [CHU Pitié-Salpêtrière], Service des Pathologies du sommeil [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Multiple Sleep Latency Test, Flumazenil, Cataplexy, [SDV]Life Sciences [q-bio], Excessive daytime sleepiness, Modafinil, Idiopathic Hypersomnia, Hypnotic, chemistry.chemical_compound, 0302 clinical medicine, Piperidines, Precision Medicine, medicine.diagnostic_test, Wakefulness-Promoting Agents, General Medicine, Mazindol, 3. Good health, Psychiatry and Mental health, Clinical Psychology, Neuropsychology and Physiological Psychology, Spiperone, Anesthesia, Female, Sleep onset, medicine.symptom, Sodium Oxybate, medicine.drug, Pitolisant, medicine.drug_class, Polysomnography, Disorders of Excessive Somnolence, 03 medical and health sciences, Clarithromycin, mental disorders, medicine, Humans, Wakefulness, GABA Modulators, Narcolepsy, Orexins, business.industry, medicine.disease, 030228 respiratory system, chemistry, Central Nervous System Stimulants, Neurology (clinical), business, Sleep, 030217 neurology & neurosurgery
Abstract: Idiopathic hypersomnia (IH) is characterized by excessive daytime sleepiness despite normal or prolonged sleep. IH is distinguished from narcolepsy by the female predominance, severe morning inertia, continuous drowsiness (rather than sleep attacks), unrefreshing naps, absence of cataplexy, sleep onset in REM periods, and hypocretin deficiency. In IH, the multiple sleep latency test demonstrates low sensitivity, specificity, and reproducibility, compared with prolonged sleep monitoring. In some IH cases, an endogenous hypnotic peptide stimulating GABA receptors during wakefulness is suspected, which are improved by anti-GABA drugs. The benefits of modafinil, sodium oxybate, mazindol, and pitolisant were found in mostly retrospective studies.
Published: 2022
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21. Investigating drug resistance of Mycobacterium leprae in the Comoros: an observational deep-sequencing study

Author: Sofie Marijke Braet, Agathe Jouet, Alexandra Aubry, Magalie Van Dyck-Lippens, Esteban Lenoir, Younoussa Assoumani, Abdallah Baco, Aboubacar Mzembaba, Emmanuelle Cambau, Sidra Ezidio Gonçalves Vasconcellos, Leen Rigouts, Philip Noel Suffys, Epco Hasker, Philip Supply, Bouke Catherine de Jong, University of Antwerp (UA), Institute of Tropical Medicine [Antwerp] (ITM), Genoscreen [Lille], Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Mycobactéries et de la Résistance aux Antituberculeux [CHU Pitié-Salpêtrière] (CNR-MyRMA), 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), Damien Foundation, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Instituto Oswaldo Cruz / Oswaldo Cruz Institute [Rio de Janeiro] (IOC), Fundação Oswaldo Cruz (FIOCRUZ), 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), CHU Lille, Supply, Philip, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ)
Subjects: Microbiology (medical), [SDV.GEN]Life Sciences [q-bio]/Genetics, Leprostatic Agents, [SDV.GEN] Life Sciences [q-bio]/Genetics, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Microbiology, Comoros, Mycobacterium leprae, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Leprosy, Virology, Drug Resistance, Bacterial, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Drug Therapy, Combination, Human medicine, Rifampin, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Dapsone, Biology
Abstract: Despite strong leprosy control measures, including effective treatment, leprosy persists in the Comoros. As of May, 2022, no resistance to anti-leprosy drugs had been reported, but there are no nationally representative data. Post-exposure prophylaxis (PEP) with rifampicin is offered to contacts of patients with leprosy. We aimed to conduct a countrywide drug resistance survey and investigate whether PEP led to the emergence of drug resistance in patients with leprosy.In this observational, deep-sequencing analysis we assessed Mycobacterium leprae genomes from skin biopsies of patients in Anjouan and Mohéli, Comoros, collected as part of the ComLep (NCT03526718) and PEOPLE (NCT03662022) studies. Skin biopsies that had sufficient M leprae DNA (2000 bacilli in 2 μl of DNA extract) were assessed for the presence of seven drug resistance-associated genes (ie, rpoB, ctpC, ctpI, folP1, gyrA, gyrB, and nth) using Deeplex Myc-Lep (targeted next generation deep sequencing), with a limit of detection of 10% for minority M leprae bacterial populations bearing a polymorphism in these genes. All newly registered patients with leprosy for whom written informed consent was obtained were eligible for inclusion in the survey. Patients younger than 2 years or with a single lesion on the face did not have biopsies taken. The primary outcome of our study was the proportion of patients with leprosy (ie, new cases, patients with relapses or reinfections, patients who received single (double) dose rifampicin-PEP, or patients who lived in villages where PEP was distributed) who were infected with M leprae with a drug-resistant mutation for rifampicin, fluoroquinolone, or dapsone in the Comoros.Between July 1, 2017, and Dec 31, 2020, 1199 patients with leprosy were identified on the basis of clinical criteria, of whom 1030 provided a skin biopsy. Of these 1030 patients, 755 (73·3%) tested positive for the M leprae-specific repetitive element-quantitative PCR (qPCR) assay. Of these 755 patients, 260 (34·4%) were eligible to be analysed using Deeplex Myc-Lep. 251 (96·5%) were newly diagnosed with leprosy, whereas nine (3·4%) patients had previously received multidrug therapy. 45 (17·3%) patients resided in villages where PEP had been administered in 2015 or 2019, two (4·4%) of whom received PEP. All seven drug resistance-associated targets were successfully sequenced in 216 samples, 39 samples had incomplete results, and five had no results. No mutations were detected in any of the seven drug resistance-related genes for any patient with successfully sequenced results.This drug resistance survey provides evidence to show that M leprae is fully susceptible to rifampicin, fluoroquinolones, and dapsone in the Comoros. Our results also show, for the first time, the applicability of targeted sequencing directly on skin biopsies from patients with either paucibacillary or multibacillary leprosy. These data suggest that PEP had not selected rifampicin-resistant strains, although further support for this finding should be confirmed with a larger sample size.Effect:Hope, The Mission To End Leprosy, the Fonds Wetenschappelijk Onderzoek, the EU.
Published: 2022
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22. Understanding functional neurological disorders: From biological markers to pathophysiological models

Author: Conejero, Ismael, Thouvenot, Eric, Hingray, Coraline, Hubsch, Cécile, El-Hage, Wissam, Carle-Toulemonde, Guilhem, Rotge, Jean-Yves, Drapier, Sophie, Drapier, Dominique, Mouchabac, Stéphane, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Génomique Fonctionnelle - Montpellier GenomiX (IGF MGX), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Psychothérapique de Nancy [Laxou] (CPN), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Clinique Psychiatrique Universitaire [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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], Université de Rennes (UR), Centre Hospitalier Guillaume Régnier [Rennes], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and None
Subjects: [SDV]Life Sciences [q-bio], Neurosciences, Neuroimaging, Trouble neurologique fonctionnel, Functional neurological disorders, Stress, Neuroimagerie, Neuroscience
Abstract: National audience; OBJECTIVES: Functional neurological disorders have witnessed intense research activity in the fields of structural and functional neuroimaging for more than twenty years. Thus, we propose a synthesis of recent research findings and etiological hypotheses that have been proposed so far. This work should help clinicians to better understand the nature of the mechanisms involved, but also help patients to increase their knowledge about the biological features underlying their functional symptoms. METHODS: We carried out a narrative review of international publications dealing with neuroimaging and biology of functional neurological disorders, from 1997 to 2023. RESULTS: Several brain networks underlie functional neurological symptoms. These networks play a role in the management of cognitive resources, in attentional control, emotion regulation, in agency and in the processing of interoceptive signals. The mechanisms of the stress response are also associated with the symptoms. The biopsychosocial model helps to better understand predisposing, precipitating, and perpetuating factors involved. The functional neurological phenotype results from the interaction between: i) a specific pre-existing vulnerability resulting from biological background and epigenetic modifications, and ii) exposure to stress factors, according to the stress-diathesis model. This interaction causes emotional disturbances including hypervigilance, lack of integration of sensations and affects, and emotional dysregulation. These characteristics in turn impact the cognitive, motor and affective control processes related with the functional neurological symptoms. CONCLUSIONS: A better knowledge of the biopsychosocial determinants of brain network dysfunctions is necessary. Understanding them would help developing targeted treatments, but is also critical for patients care.
Published: 2023
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23. Congenital mirror movements are associated with defective polymerization of RAD51

Author: Trouillard, Oriane, Dupaigne, Pauline, Dunoyer, Margaux, Doulazmi, Mohamed, Herlin, Morten Krogh, Frismand, Solène, Riou, Audrey, Legros, Véronique, Chevreux, Guillaume, Veaute, Xavier, Busso, Didier, Fouquet, Coralie, Saint-Martin, Cécile, Méneret, Aurélie, Trembleau, Alain, Dusart, Isabelle, Dubacq, Caroline, Roze, Emmanuel, Développement et plasticité des réseaux neuronaux = Development and Plasticity of Neural Networks (NPS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Mouvement, Investigations, Thérapeutique. Mouvement normal et anormal : physiopathologie et thérapeutique expérimentale [ICM Paris] (Mov’It), 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)-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), Maintenance des génomes, Microscopies Moléculaire et Bionanosciences, Centre National de la Recherche Scientifique-Université Paris Sud, Maintenance des génomes, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Departement of clinical genetics, Aarhus University Hospital, Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de génétique clinique [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, Service de neurologie [Rennes], Université de Rennes (UR), Université de Paris, CNRS, Institut Jacques Monod, Paris, France, Stabilité génétique, cellules souches et radiations (SGCSR (U_1274 / UMR_E_008)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Développement, évolution et plasticité du système nerveux (DEPSN), Centre National de la Recherche Scientifique (CNRS), This work was supported by the Fondation Desmarest, Merz-Pharma, Elivie, Orkyn, Djillali Mehri, CNRS, INSERM and Sorbonne Université. This work was also funded by grants from the Agence Nationale de la Recherche (ANR) (ANR-14-CE13-0004-01, ANR-18-CE16-0005-02), from the National Institute of Health NIDCD (R01-DC-017989, USA) and it was performed within the framework of LABEX LIFESENSES (ANR- 10-LABX-65) supported by French state funds managed by the ANR within the Investissements d’Avenir program (ANR-11-IDEX-0004-02)., ANR-18-CE16-0005,Momic,La décussation du faisceau corticospinal et la latéralisation du contrôle moteur : le paradigme des Mouvements Miroirs Congénitaux (MoMiC)(2018), ANR-14-CE13-0004,AxoDevo,Evolution du guidage axonal(2014), and ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience; Background. Mirror movements are involuntary movements of one hand that mirror intentional movements of the other hand. Congenital mirror movements (CMM) is a rare genetic disorder with autosomal dominant inheritance, in which mirror movements are the main neurological manifestation. CMM is associated with an abnormal decussation of the corticospinal tract, a major motor tract for voluntary movements. RAD51 is known to play a key role in homologous recombination with a critical function in DNA repair. While RAD51 haploinsufficiency was first proposed to explain CMM, other mechanisms could be involved. Methods. We performed Sanger sequencing of RAD51 in five newly identified CMM families to identify new pathogenic variants. We further investigated the expression of wild-type and mutant RAD51 in the patients' lymphoblasts at mRNA and protein levels. We then characterized the functions of RAD51 altered by non-truncating variants using biochemical approaches. Results. The level of wild-type RAD51 protein was lower in all the CMM patients' cells compared with their non-carrier relatives. The reduction was less pronounced in asymptomatic carriers. In vitro, mutant RAD51 proteins showed loss-of-function for polymerization, DNA binding, and strand exchange activity. Conclusion. Our study demonstrates that RAD51 haploinsufficiency, including loss-offunction of non-truncating variants, results in CMM. The incomplete penetrance likely results from post-transcriptional compensation. Changes in RAD51 levels and/or polymerization properties could influence guidance of the corticospinal axons during development. Our findings open up new perspectives to understand the role of RAD51 in neurodevelopment.
Published: 2023
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24. Ensemble of Riemannian classifiers for multimodal data: FUCONE approach for M/EEG data

Author: Corsi, Marie-Constance, Chevallier, Sylvain, de Vico Fallani, Fabrizio, Yger, Florian, Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Interdisciplinaire des Sciences du Numérique (LISN), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'analyse et modélisation de systèmes pour l'aide à la décision (LAMSADE), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Groupe de Recherche en Informatique, Image et Instrumentation de Caen (GREYC), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), BCI Society, ANR-19-P3IA-0001,PRAIRIE,PaRis Artificial Intelligence Research InstitutE(2019), European Project: 864729,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC),BCINET(2020), Machine Intelligence and Learning Systems (MILES), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Dauphine-PSL
Subjects: [SCCO.NEUR]Cognitive science/Neuroscience, [INFO]Computer Science [cs]
Abstract: International audience; Controlling a brain-computer interface (BCI) requires time to achieve high performance. Despite its clinical applications, one of the main drawbacks is the high inter-subject variability that could be noticed for performance. This is sometimes referred in the literature as the « BCI inefficiency » phenomenon and affects its usability. Among the approaches adopted to tackle these issues are the search for neuromarkers that potentially capture better the neurophysiological mechanisms underlying the BCI performance and the optimization of the classification pipelines, that could be robust enough to be applied to any subject. In this work, we proposed an original approach that combines functional connectivity estimators, Riemannian geometry and ensemble learning to ensure a robust classification.
Published: 2023

25. Reproducibility in machine learning for medical imaging

Author: Colliot, Olivier, Thibeau-Sutre, Elina, Burgos, Ninon, Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Department of Applied Mathematics [Twente], University of Twente, Olivier Colliot, and ANR-19-P3IA-0001,PRAIRIE,PaRis Artificial Intelligence Research InstitutE(2019)
Subjects: Artificial intelligence, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], Deep learning, Reliability, Reproducibility, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], [STAT.ML]Statistics [stat]/Machine Learning [stat.ML], [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Replicability, Machine learning, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Repeatability, Open science, Medical imaging, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing
Abstract: International audience; Reproducibility is a cornerstone of science, as the replication of findings is the process through which they become knowledge. It is widely considered that many fields of science are undergoing a reproducibility crisis. This has led to the publications of various guidelines in order to improve research reproducibility. This didactic chapter intends at being an introduction to reproducibility for researchers in the field of machine learning for medical imaging. We first distinguish between different types of reproducibility. For each of them, we aim at defining it, at describing the requirements to achieve it and at discussing its utility. The chapter ends with a discussion on the benefits of reproducibility and with a plea for a non-dogmatic approach to this concept and its implementation in research practice.
Published: 2023

26. L’esprit predictif : introduction à la théorie du cerveau bayésien

Author: BOTTEMANNE, Hugo, Longuet, Y., GAULD, C., Service de Psychiatrie Adulte [CHU Pitié-Salpêtière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de médecine [CHU Pitié Salpétrière], Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sciences, Normes, Démocratie [Paris] (SND), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Université Grenoble Alpes (UGA)
Subjects: Psychiatry and Mental health, Arts and Humanities (miscellaneous), [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.PSYC]Cognitive science/Psychology, [SHS.PHIL]Humanities and Social Sciences/Philosophy, [SHS.PSY]Humanities and Social Sciences/Psychology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2022
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27. High SARS-CoV-2 seroprevalence in HIV patients originating from sub-Saharan Africa in the Ile-de-France area

Author: Basma ABDI, Aude Laetitia NDOADOUMGUE, Siham DJEBARA, Karen ZAFILAZA, Romain PALICH, Stéphane MAROT, Luminata SCHNEIDER, Marc WIRDEN, Sophie SEANG, Yasmine DUDOIT, Elisa TEYSSOU, Roland TUBIANA, Cathia SOULIE, Marc Antoine VALANTIN, Christine KATLAMA, Vincent CALVEZ, Lambert ASSOUMOU, Anne-Geneviève MARCELIN, Valérie POURCHER, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], and ABDI, BASMA
Subjects: [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Microbiology (medical), [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, seroprevalence, SARS-CoV-2, COVID-19, HIV, humoral immune response, Infectious Diseases, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, risk factors, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: International audience; Objectives: We studied the kinetics of SARS-CoV-2 antibodies and identified the associated risk factors with the presence of these antibodies.Methods: In this longitudinal cohort study, we included all PLWHIV. Samples were tested for IgG targeting the nucleocapsid (N) and all positive samples were tested for IgG targeting the spike (S) and IgA targeting S.Results: 1,901 PLWHIV were included: 64.4% male, median age: 53 years (44-60). At inclusion, 254 (13.4%, 95% CI 11.9, 15.0) had positive IgG anti-N. Levels of IgG anti-N, IgG anti-S and IgA anti-S were 3.95 (standard error: 0.16), 199.4 BAU/mL (21.7) and 3.14 (0.21), respectively. Over one year, levels of IgG anti-N and anti-S decreased significantly (-2.83 p
Published: 2022
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28. Treatment times, functional outcome, and hemorrhage rates after switching to tenecteplase for stroke thrombolysis: Insights from the TETRIS registry

Author: Gaspard Gerschenfeld, Jean-Sébastien Liegey, François-Xavier Laborne, Marion Yger, Victoire Lyon, Thomas Checkouri, Bertille Tricard-Dessagne, Gaultier Marnat, Frédéric Clarençon, Nicolas Chausson, Guillaume Turc, Igor Sibon, Sonia Alamowitch, Stéphane Olindo, Service d'Urgences Cérébro-Vasculaires [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Infrastructure de recherche clinique en psychiatrie adulte [ICM Paris] (iCRIN psychiatrie), 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)-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)-Département Médico-Universitaire Neurosciences [Sorbonne Université] (DMU Neurosciences), CHU Charles Foix [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 Tenon [AP-HP], 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)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Tenon [AP-HP], CHU Bordeaux [Bordeaux], Centre Hospitalier Sud Francilien, Sorbonne Université (SU), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), GHU Paris Psychiatrie et Neurosciences, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de neurologie [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, and Gerschenfeld, Gaspard
Subjects: thrombolysis, Ischemic stroke, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, tenecteplase, process times, Original Research Articles, Neurology (clinical), acute stroke therapy, Cardiology and Cardiovascular Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Introduction: The encouraging efficacy and safety data on intravenous thrombolysis with tenecteplase in ischemic stroke and its practical advantages motivated our centers to switch from alteplase to tenecteplase. We report its impact on treatment times and clinical outcomes. Methods: We retrospectively analyzed clinical and procedural data of patients treated with alteplase or tenecteplase in a comprehensive (CSC) and a primary stroke center (PSC), which transitioned respectively in 2019 and 2018. Tenecteplase enabled in-imaging thrombolysis in the CSC. The main outcomes were the imaging-to-thrombolysis and thrombolysis-to-puncture times. We assessed the association of tenecteplase with 3-month functional independence and parenchymal hemorrhage (PH) with multivariable logistic models. Results: We included 795 patients, 387 (48.7%) received alteplase and 408 (51.3%) tenecteplase. Both groups (tenecteplase vs alteplase) were similar in terms of age (75 vs 76 years), baseline NIHSS score (7 vs 7.5) and proportion of patients treated with mechanical thrombectomy (24.1% vs 27.5%). Tenecteplase patients had shorter imaging-to-thrombolysis times (27 vs 36 min, p a 1.68, 95% CI 1.15–2.48, p a 0.68, 95% CI 0.41–1.12, p = 0.13). Conclusion: Switch from alteplase to tenecteplase reduced process times and may improve functional outcome, with similar safety profile.
Published: 2022
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29. Bleeding and thrombotic events in patients with severe COVID-19 supported with extracorporeal membrane oxygenation: a nationwide cohort study

Author: Mansour, Alexandre, Flecher, Erwan, Schmidt, Matthieu, Rozec, Bertrand, Gouin-Thibault, Isabelle, Esvan, Maxime, Fougerou, Claire, Levy, Bruno, Porto, Alizée, Ross, James, Para, Marylou, Manganiello, Sabrina, Lebreton, Guillaume, Vincentelli, André, Nesseler, Nicolas, Pierrot, Marc, Chocron, Sidney, Flicoteaux, Guillaume, Mauriat, Philippe, Ouattara, Alexandre, Roze, Hadrien, Huet, Olivier, Fischer, Marc-Olivier, Alessandri, Claire, Bellaïche, Raphel, Constant, Ophélie, de Roux, Quentin, Ly, André, Meffert, Arnaud, Merle, Jean-Claude, Mongardon, Nicolas, Picard, Lucile, Skripkina, Elena, Folliguet, Thierry, Fiore, Antonio, D’ostrevy, Nicolas, Morgan, Marie-Catherine, Guinot, Pierre-Grégoire, Nguyen, Maxime, Gaide-Chevronnay, Lucie, Terzi, Nicolas, Colin, Gwenhaël, Fabre, Olivier, Astaneh, Arash, Issard, Justin, Fadel, Elie, Fabre, Dominique, Girault, Antoine, Guihaire, Julien, Ion, Iolande, Menager, Jean Baptiste, Mitilian, Delphine, Mercier, Olaf, Stephan, François, Thes, Jacques, Jouan, Jerôme, Duburcq, Thibault, Loobuyck, Valentin, Moussa, Mouhammed, Mugnier, Agnes, Rousse, Natacha, Desebbe, Olivier, Fellahi, Jean-Luc, Henaine, Roland, Pozzi, Matteo, Richard, Jean-Christophe, Riad, Zakaria, Guervilly, Christophe, Hraiech, Sami, Papazian, Laurent, Castanier, Matthias, Chanavaz, Charles, Cadoz, Cyril, Gette, Sebastien, Louis, Guillaume, Portocarrero, Erick, Gaudard, Philippe, Brini, Kais, Bischoff, Nicolas, Kimmoun, Antoine, Mattei, Mathieu, Perez, Pierre, Bourdiol, Alexandre, Hourmant, Yannick, Mahé, Pierre-Joachim, Jaquet, Pierre, Lortat-Jacob, Brice, Mordant, Pierre, Nataf, Patrick, Patrier, Juliette, Provenchère, Sophie, Roué, Morgan, Sonneville, Romain, Tran-Dinh, Alexy, Wicky, Paul-Henri, Al Zreibi, Charles, Cholley, Bernard, Guyonvarch, Yannis, Hamada, Sophie, Harrois, Anatole, Matiello, Jordi, Kerforne, Thomas, Lacroix, Corentin, Brechot, Nicolas, Combes, Alain, Chommeloux, Juliette, Constantin, Jean Michel, D’alessandro, Cosimo, Demondion, Pierre, Demoule, Alexandre, Dres, Martin, Fadel, Guillaume, Fartoukh, Muriel, Hekimian, Guillaume, Juvin, Charles, Leprince, Pascal, Levy, David, Luyt, Charles Edouard, Pineton de Chambrun, Marc, Schoell, Thibaut, Fillâtre, Pierre, Massart, Nicolas, Nicolas, Roxane, Jonas, Maud, Vidal, Charles, Allou, Nicolas, Muccio, Salvatore, Di Perna, Dario, Ruggieri, Vito-Giovanni, Mourvillier, Bruno, Anselmi, Amedeo, Bounader, Karl, Launey, Yoann, Lebouvier, Thomas, Parasido, Alessandro, Reizine, Florian, Seguin, Philippe, Besnier, Emmanuel, Carpentier, Dorothée, Clavier, Thomas, Falcoz, Pierre-Emmanuel, Olland, Anne, Villard, Marion, Bounes, Fanny, Labaste, François, Minville, Vincent, Guillon, Antoine, Fedun, Yannick, CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), 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), Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Réanimation Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital de la Timone [CHU - APHM] (TIMONE), University of California [Davis] (UC Davis), University of California (UC), 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, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Lille, 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), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD), 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), 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), 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), and This work was supported by a grant from the university hospital of Rennes (Appel à projets CFTR2) and by a grant from the French society of thoracic and cardio-vascular surgery (Société française de chirurgie thoracique et cardio-vasculaire, Bourse Marc Laskar).
Subjects: Anticoagulation, [SDV]Life Sciences [q-bio], Bleeding, COVID-19, Thrombosis, ECMO, Critical Care and Intensive Care Medicine
Abstract: International audience; Purpose: To describe bleeding and thrombotic events and their risk factors in patients receiving extracorporeal membrane oxygenation (ECMO) for severe coronavirus disease 2019 (COVID-19) and to evaluate their impact on in-hospital mortality.Methods: The ECMOSARS registry included COVID-19 patients supported by ECMO in France. We analyzed all patients included up to March 31, 2022 without missing data regarding bleeding and thrombotic events. The association of bleeding and thrombotic events with in-hospital mortality and pre-ECMO variables was assessed using multivariable logistic regression models.Results: Among 620 patients supported by ECMO, 29% had only bleeding events, 16% only thrombotic events and 20% both bleeding and thrombosis. Cannulation site (18% of patients), ear nose and throat (12%), pulmonary bleeding (9%) and intracranial hemorrhage (8%) were the most frequent bleeding types. Device-related thrombosis and pulmonary embolism/thrombosis accounted for most of thrombotic events. In-hospital mortality was 55.7%. Bleeding events were associated with in-hospital mortality (adjusted odds ratio (adjOR) = 2.91[1.94-4.4]) but not thrombotic events (adjOR = 1.02[0.68-1.53]). Intracranial hemorrhage was strongly associated with in-hospital mortality (adjOR = 13.5[4.4-41.5]). Ventilation duration before ECMO ≥ 7 days and length of ECMO support were associated with bleeding. Thrombosis-associated factors were fibrinogen ≥ 6 g/L and length of ECMO support.Conclusions: In a nationwide cohort of COVID-19 patients supported by ECMO, bleeding incidence was high and associated with mortality. Intracranial hemorrhage incidence was higher than reported for non-COVID patients and carried the highest risk of death. Thrombotic events were less frequent and not associated with mortality. Length of ECMO support was associated with a higher risk of both bleeding and thrombosis, supporting the development of strategies to minimize ECMO duration.
Published: 2022
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30. Heterogeneity of PD-MCI in Candidates to Subthalamic Deep Brain Stimulation: Associated Cortical and Subcortical Modifications

Author: Quentin, Devignes, Sami, Daoudi, Romain, Viard, Renaud, Lopes, Nacim, Betrouni, Gregory, Kuchcinski, Anne-Sophie, Rolland, Caroline, Moreau, Luc, Defebvre, Eric, Bardinet, Marie, Bonnet, Christine, Brefel-Courbon, Christine, Delmaire, Fouzia, El Mountassir, Frédérique, Fluchère, Anne, Fradet, Caroline, Giordana, Elodie, Hainque, Jean-François, Houvenaghel, Béchir, Jarraya, Hélène, Klinger, David, Maltête, Ana, Marques, Mylène, Meyer, Olivier, Rascol, Tiphaine, Rouaud, Melissa, Tir, Thomas, Wirth, Jean-Christophe, Corvol, David, Devos, Kathy, Dujardin, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, 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), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), 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)-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 Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Building large instruments for neuroimaging: from population imaging to ultra-high magnetic fields (BAOBAB), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHU Nice], Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), 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), Centre Hospitalier Universitaire [Rennes], Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hôpital Foch [Suresnes], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), 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), Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA), CHU Clermont-Ferrand, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Amiens-Picardie, Les Hôpitaux Universitaires de Strasbourg (HUS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and ANR-10-IAIHU-06
Subjects: [SCCO.NEUR]Cognitive science/Neuroscience, Deep Brain Stimulation, shape analysis, Parkinson Disease, Magnetic Resonance Imaging, Cortical thickness, Cellular and Molecular Neuroscience, Cognition, radiomics, dual syndrome hypothesis, voxel-based morphometry, Humans, Cognitive Dysfunction, Neurology (clinical)
Abstract: International audience; Background: Parkinson’s disease mild cognitive impairment (PD-MCI) is frequent and heterogenous. There is no consensus about its influence on subthalamic deep brain stimulation (STN-DBS) outcomes. Objective: To determine the prevalence of PD-MCI and its subtypes in candidates to STN-DBS. Secondarily, we sought to identify MRI structural markers associated with cognitive impairment in these subgroups. Methods: Baseline data from the French multicentric PREDISTIM cohort were used. Candidates to STN-DBS were classified according to their cognitive performance in normal cognition (PD-NC) or PD-MCI. The latter included frontostriatal (PD-FS) and posterior cortical (PD-PC) subtypes. Between-group comparisons were performed on demographical and clinical variables as well as on T1-weighted MRI sequences at the cortical and subcortical levels. Results: 320 patients were included: 167 (52%) PD-NC and 153 (48%) PD-MCI patients. The latter group included 123 (80%) PD-FS and 30 (20%) PD-PC patients. There was no between-group difference regarding demographic and clinical variables. PD-PC patients had significantly lower global efficiency than PD-FS patients and significantly worse performance on visuospatial functions, episodic memory, and language. Compared to PD-NC, PD-MCI patients had cortical thinning and radiomic-based changes in the left caudate nucleus and hippocampus. There were no significant differences between the PD-MCI subtypes. Conclusion: Among the candidates to STN-DBS, a significant proportion has PD-MCI which is associated with cortical and subcortical alterations. Some PD-MCI patients have posterior cortical deficits, a subtype known to be at higher risk of dementia.
Published: 2022
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31. Effect of bimekizumab on symptoms and impact of disease in patients with psoriatic arthritis over 3 years: results from BE ACTIVE

Author: Philip J Mease, Akihiko Asahina, Dafna D Gladman, Yoshiya Tanaka, William Tillett, Barbara Ink, Deepak Assudani, Christine de la Loge, Jason Coarse, Jason Eells, Laure Gossec, University of Washington [Seattle], Swedish Medical Center [Seattle, WA, USA], The Jikei University School of Medicine, University of Toronto, University of Occupational and Environmental Health [Kitakyushu] (UEOH), University of Bath [Bath], UCB Pharma [Slough], UCB Pharma [Brussels], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and HAL-SU, Gestionnaire
Subjects: [SDV] Life Sciences [q-bio], physical function, Rheumatology, Psoriatic arthritis, [SDV]Life Sciences [q-bio], fatigue, pain, Pharmacology (medical), bimekizumab, patient-reported outcome measures
Abstract: Objectives Evaluate effects of long-term bimekizumab treatment on patient-reported outcome (PRO) measures, symptoms and the impact of PsA on patients. Methods Patients with active PsA were enrolled into BE ACTIVE, a 48-week randomised controlled trial (NCT02969525). After Week 48, patients could enter a 104-week open-label extension (NCT03347110), receiving bimekizumab 160 mg every four weeks. PRO measures assessed included arthritis pain visual analogue scale (VAS), PsA Impact of Disease (PsAID)-9, 36-Item Short Form Survey (SF-36) and HAQ-Disability Index (HAQ-DI). Results were analysed as mean (S.E.M.) changes from baseline (CfB) from Week 0 to the end of the open-label extension (3 years) and as percentage of patients reaching patient-acceptable symptom state (PASS) for global impact (PsAID-9 total score ≤4) and normal function (HAQ-DI total score Results In 206 patients (mean age 49.3 years, 51.0% male), completion rate was high; 161 (78.2%) patients completed Week 152. Bimekizumab treatment was associated with long-term sustained improvements in pain [arthritis pain VAS CfB; Week 48: −29.9 (1.9); Week 152: −32.0 (1.9)] and fatigue [PsAID-9 fatigue CfB; −2.4 (0.2); −2.7 (0.2)]. High percentages of patients achieved acceptable symptom state (PsAID-9 PASS: 75.2%; 65.0%) and normalised function (HAQ-DI Conclusions Bimekizumab treatment was associated with long-term sustained improvements in pain and fatigue, reducing overall impact of PsA on patients. Physical function and quality of life improved up to 3 years. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT02969525, NCT03347110.
Published: 2022
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32. Should proximal ruptures of the anterior rectus femoris muscle be treated surgically?

Author: Olivier Barbier, Frédéric Khiami, Choufani Camille, Hopital d'instruction des armées Sainte-Anne [Toulon] (HIA), Service de Chirurgie Orthopédique et Traumatologique [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), Service de chirurgie orthopédique et traumatologique [CHU Pitié-Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Quadriceps muscle, medicine.medical_specialty, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Rectus femoris muscle, Tendons, Course of action, Lesion, Avulsion, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Hematoma, Tendinitis, Suture (anatomy), Tendon Injuries, medicine, Humans, Orthopedics and Sports Medicine, Fisher's exact test, Rupture, 030222 orthopedics, business.industry, 030229 sport sciences, medicine.disease, Avulsion fractures, 3. Good health, Surgery, Tendinopathy, symbols, medicine.symptom, business
Abstract: International audience; Purpose: No therapeutic consensus has been established about proximal ruptures of the rectus femoris muscle. The objective of this literature review is to determine a therapeutic course of action. Methods: We conducted a literature review on the PubMed database using the following keywords (in French and English, respectively): "quadriceps/quadriceps", "droit ant erieur/rectus femoris", "proximal/ proximal", "chirurgie/surgical", "avulsion/avulsion". We collected 266 articles, 36 of them were selected, which were related to our topic: proximal rupture of the anterior rectus femoris. Patients with a proximal rupture of the rectus femoris, minor or major patient of traumatic origin were included in this study. Patients injured at another lesion level, or non-traumatic lesions of the proximal rectus femoris (tendinitis without ruptures, tumor or others) were excluded. For each patient, the indications, the type of treatment and the functional result were analyzed, with the time to recovery and the level of recovery from sports and professional activities (same sport/profession or not, same level or not) as the main criterion of judgment. Fisher exact test was used for statistical comparison. Results: The aims of conservative treatment are to be pain free for the patient, to fight hematoma and to rehabilitate the injury as quickly as possible. The surgical techniques are varied, with most consisting of either a reinsertion of the musculo-tendon stump or a resection of the scar tissue with myo-tendinoaponeurotic suture in place. The functional results are good for the majority of the treatments proposed, but the conservative treatment has a shorter recovery time (3 months vs. 4 months for the best surgical results). Highly displaced bone avulsion is the only indication for first-line surgical treatment. Conclusion: The main disadvantage of conservative treatment is the risk of residual pain beyond 3 months (10%), justifying an MRI to guide secondary surgical treatment. We propose a treatment plan for proximal rupture of the proximal rectus femoris rupture.
Published: 2022
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33. Phenotypic Heterogeneity of Fulminant COVID-19--Related Myocarditis in Adults

Author: Petra Barhoum, Marc Pineton de Chambrun, Karim Dorgham, Mathieu Kerneis, Sonia Burrel, Paul Quentric, Christophe Parizot, Juliette Chommeloux, Nicolas Bréchot, Quentin Moyon, Guillaume Lebreton, Samia Boussouar, Matthieu Schmidt, Hans Yssel, Lucie Lefevre, Makoto Miyara, Jean-Luc Charuel, Stéphane Marot, Anne-Geneviève Marcelin, Charles-Edouard Luyt, Pascal Leprince, Zahir Amoura, Gilles Montalescot, Alban Redheuil, Alain Combes, Guy Gorochov, Guillaume Hékimian, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), 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 E3M [CHU Pitié-Salpêtrière], Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Dorgham, Karim
Subjects: [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Adult, Male, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Adolescent, SARS-CoV-2, COVID-19, Stroke Volume, Middle Aged, Systemic Inflammatory Response Syndrome, Ventricular Function, Left, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Myocarditis, Young Adult, Phenotype, [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.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Cardiology and Cardiovascular Medicine, Autoantibodies, Retrospective Studies
Abstract: International audience; Background: Adults who have been infected with SARS-CoV-2 can develop a multisystem inflammatory syndrome (MIS-A), including fulminant myocarditis. Yet, several patients fail to meet MIS-A criteria, suggesting the existence of distinct phenotypes in fulminant COVID-19–related myocarditis.Objectives: This study sought to compare the characteristics and clinical outcome between patients with fulminant COVID-19–related myocarditis fulfilling MIS-A criteria (MIS-A+) or not (MIS-A−).Methods: A monocentric retrospective analysis of consecutive fulminant COVID-19–related myocarditis in a 26-bed intensive care unit (ICU).Results: Between March 2020 and June 2021, 38 patients required ICU admission (male 66%; mean age 32 ± 15 years) for suspected fulminant COVID-19–related myocarditis. In-ICU treatment for organ failure included dobutamine 79%, norepinephrine 60%, mechanical ventilation 50%, venoarterial extracorporeal membrane oxygenation 42%, and renal replacement therapy 29%. In-hospital mortality was 13%. Twenty-five patients (66%) met the MIS-A criteria. MIS-A− patients compared with MIS-A+ patients were characterized by a shorter delay between COVID-19 symptoms onset and myocarditis, a lower left ventricular ejection fraction, and a higher rate of in-ICU organ failure, and were more likely to require mechanical circulatory support with venoarterial extracorporeal membrane oxygenation (92% vs 16%; P < 0.0001). In-hospital mortality was higher in MIS-A− patients (31% vs 4%). MIS-A+ had higher circulating levels of interleukin (IL)-22, IL-17, and tumor necrosis factor-α (TNF-α), whereas MIS-A− had higher interferon-α2 (IFN-α2) and IL-8 levels. RNA polymerase III autoantibodies were present in 7 of 13 MIS-A− patients (54%) but in none of the MIS-A+ patients.Conclusion: MIS-A+ and MIS-A− fulminant COVID-19–related myocarditis patients have 2 distinct phenotypes with different clinical presentations, prognosis, and immunological profiles. Differentiating these 2 phenotypes is relevant for patients’ management and further understanding of their pathophysiology
Published: 2022
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34. The scaffold-dependent function of RIPK1 in experimental non-alcoholic steatohepatitis

Author: Valeria Pistorio, Juliette Tokgozoglu, Vlad Ratziu, Jérémie Gautheron, University of Naples Federico II, Centre de Recherche Saint-Antoine (CRSA), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Non-alcoholic Fatty Liver Disease, Receptor-Interacting Protein Serine-Threonine Kinases, [SDV]Life Sciences [q-bio], Drug Discovery, Humans, Molecular Medicine, ComputingMilieux_MISCELLANEOUS, Genetics (clinical)
Abstract: International audience; No abstract available
Published: 2022
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35. Trajectory Pattern of Cognitive Decline in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy

Author: Sandrine Brice, Sonia Reyes, Aude Jabouley, Carla Machado, Christina Rogan, Nathalie Gastellier, Nassira Alili, Stephanie Guey, Eric Jouvent, Dominique Hervé, Sophie Tezenas du Montcel, Hugues Chabriat, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical)
Abstract: Background and ObjectivesThe course and pattern of cognitive decline in ischemic cerebral small vessel disease remain poorly characterized. We analyzed the trajectory pattern of cognitive decline from age 25 to 75 years in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).MethodsWe applied latent process mixed models to data obtained from patients with CADASIL who were repeatedly scored during their follow-up using 16 selected clinical scales or cognitive tests.ResultsThe modeled evolutions of these scores obtained from 1,243 observations in 265 patients recruited at the French National Referral Centre (50.1 years on average and 45.3% men) showed wide and heterogeneous variations in amplitude along the age-related progression of the disease. Although the Backward Digit Span remained essentially stable, a linear deterioration of scores obtained using the Symbol Digit Numbers or Number of Errors of Trail Making Test B was detected from 25 to 75 years. By contrast, the largest score changes were observed at midlife using the Digit Cancellation Task. All other tests related to executive functions, memory performances, or global cognitive efficiency showed a rate of change accelerating especially at the advanced stage of the disease. Male gender and the presence of gait disorders or of some disability at baseline were found to predict earlier or large changes of 4 scores (Index of Sensitivity to Cueing, Delayed Total Recall, Initiation/Perseveration, and Barthel Index) in a subgroup of individuals distinct from the rest of the sample.DiscussionCognitive alterations develop heterogeneously during the progression of CADASIL and vary largely according to the stage of the disease. These results suggest that not only the target population and study duration but also the stage of disease progression should be considered in preparing future clinical trials aimed at reducing cognitive decline in any such condition.
Published: 2022
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36. Nicotine patches in patients on mechanical ventilation for severe COVID-19: a randomized, double-blind, placebo-controlled, multicentre trial

Author: Labro, Guylaine, Tubach, Florence, Belin, Lisa, Dubost, Jean-Louis, Osman, David, Muller, Grégoire, Quenot, Jean-Pierre, da Silva, Daniel, Zarka, Jonathan, Turpin, Matthieu, Mayaux, Julien, Lamer, Christian, Doyen, Denis, Chevrel, Guillaume, Plantefeve, Gaétan, Demeret, Sophie, Piton, Gaël, Manzon, Cyril, Ochin, Evelina, Gaillard, Raphael, Dautzenberg, Bertrand, Baldacini, Mathieu, Lebbah, Said, Miyara, Makoto, Pineton de Chambrun, Marc, Amoura, Zahir, Combes, Alain, Palmyre, Jessica, Gimeno, Linda, Kone, Assitan, Vialette, Cedric, Slimi, Ouramdane, Chommeloux, Juliette, Lefevre, Lucie, Schmidt, Matthieu, Hekimian, Guillaume, Luyt, Charles-Edouard, Stiel, Laure, Dureau, Anne-Florence, Khaldoun, Kuteifan, Eid, Hanna, Baldacini, Matthieu, Zyberfajn, Cecile, Manson, Julien, Charrier, Nathanael, Balabanian, Angelique, Contou, Damien, Pajot, Olivier, Fraisse, Megan, Desaint, Paul, Sarfati, Florence, Fartoukh, Muriel, Voirot, Guillaume, Elabbabi, Alexandre, Djibre, Michel, Desnos, Cyrielle, Garcon, Pierre, van Vong, Ly, Issad, Andrea, Pillot, Bertrand, Reither, Delphine, Rouge, Patrick, Foliot, Pascale, Bendjamar, Lynda, Pointurier, Valentin, Winiszewski, Hadrien, Capellier, Gilles, Navellou, Jean-Christophe, Tapponnier, Romain, Panicucci, Emilie, Morand, Lucas, Dellamonica, Jean, Saccheri, Clement, Weiss, Nicolas, Marois, Clemence, Le Guennec, Loic, Rohaut, Benjamin, Ensenat, Luis, Billiou, Cecilia, Aroca, Maria, Baron, Marie, Demoule, Alexandre, Beurton, Alexandra, Bureau, Come, Decavele, Maxens, Dres, Martin, Bayle, Frederique, Le, Quoc Viet, Liron, Lionel, Putegnat, Jean-Baptiste, Salord, Francois, Andreu, Pascal, Slimani, Hakim, Roudeau, Baptiste, Labruyere, Marie, Jacquier, Marine, Anguel, Nadia, Ayed, Soufia, Durand, Edgard, Guerin, Laurent, Lai, Christopher, Aboab, Jerome, Alviset, Sophie, Laine, Laurent, Azzi, Mathilde, Issoufaly, Tazime, Tric, Laurent, Knani, Lyes, Boumezrag, Chahrazad Bey, Viault, Nicolas, Barbier, Francois, Boulain, Thierry, Kamel, Toufik, Nay, Mai-Anh, Tollec, Sophie, Nguyen, an Hung, Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Département de santé publique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier René Dubos - 6, avenue de l’Ile de France 95303 CERGY-PONTOISE, Service de Pneumologie et Réanimation Respiratoire [AP-HP Hôpital Bicêtre] (DHU TORINO), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Centre de Référence de l'Hypertension Pulmonaire Sévère, Centre Hospitalier Régional d'Orléans (CHRO), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), réanimation et soins continus [CH Saint-Denis], Centre Hospitalier de Saint-Denis [Ile-de-France], Grand Hôpital de l'Est Francilien (GHEF), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département Médico-Universitaire APPROCHES, Sorbonne Université (SU), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut Mutualiste de Montsouris (IMM), Hôpital l'Archet, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Sud Francilien, Centre Hospitalier Victor Dupouy, REanimation et Soins intensifs du Patient en Insuffisance Respiratoire aigüE [CHU Pitié-Salpêtrière] (GRC RESPIRE), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Réanimation, Médipole Lyon Villeurbanne. Service de réanimation. 158 rue Léon Blum. 69100 VILLEURBANNE, France, Service de médecine intensive-réanimation Hôpital Simone Veil, Eaubonne, France, GHU Paris Psychiatrie et Neurosciences, Université Paris Cité (UPCité), Service de Pneumologie - R3S [CHU Pitié-Salpêtrière] (SPMIR-R3S), Institut Arthur Vernes, Unité de Recherche Clinique des hôpitaux Pitié-Salpêtrière – Charles Foix [CHU Pitié Salpêtrière] (URC PSL-CFX), CHU Charles Foix [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)-Direction de la Recherche Clinique et de l'Innovation [AP-HP] (DRCI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], 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), Service de Réanimation Médicale [CHU Pitié-Salpétrière], and TUBACH, Florence
Subjects: Adult, Male, Nicotine, [SDV]Life Sciences [q-bio], Acute respiratory failure, Critical Care and Intensive Care Medicine, MESH: Nicotine, Nicotinic receptor, Double-Blind Method, MESH: COVID-19, Humans, MESH: SARS-CoV-2, MESH: Double-Blind Method, MESH: Respiration, Artificial, MESH: Treatment Outcome, MESH: Humans, SARS-CoV-2, COVID-19, MESH: Adult, Respiration, Artificial, Ventilation, MESH: Male, [SDV] Life Sciences [q-bio], Intensive Care Units, Treatment Outcome, Artificial, MESH: Intensive Care Units, Female, Randomized trial, MESH: Female
Abstract: Epidemiologic studies have documented lower rates of active smokers compared to former or non-smokers in symptomatic patients affected by coronavirus disease 2019 (COVID-19). We assessed the efficacy and safety of nicotine administered by a transdermal patch in critically ill patients with COVID-19 pneumonia.In this multicentre, double-blind, placebo-controlled trial conducted in 18 intensive care units in France, we randomly assigned adult patients (non-smokers, non-vapers or who had quit smoking/vaping for at least 12 months) with proven COVID-19 pneumonia receiving invasive mechanical ventilation for up to 72 h to receive transdermal patches containing either nicotine at a daily dose of 14 mg or placebo until 48 h following successful weaning from mechanical ventilation or for a maximum of 30 days, followed by 3-week dose tapering by 3.5 mg per week. Randomization was stratified by centre, non- or former smoker status and Sequential Organ Function Assessment score ( or ≥ 7). The primary outcome was day-28 mortality. Main prespecified secondary outcomes included 60-day mortality, time to successful extubation, days alive and free from mechanical ventilation, renal replacement therapy, vasopressor support or organ failure at day 28.Between November 6th 2020, and April 2nd 2021, 220 patients were randomized from 18 active recruiting centers. After excluding 2 patients who withdrew consent, 218 patients (152 [70%] men) were included in the analysis: 106 patients to the nicotine group and 112 to the placebo group. Day-28 mortality did not differ between the two groups (30 [28%] of 106 patients in the nicotine group vs 31 [28%] of 112 patients in the placebo group; odds ratio 1.03 [95% confidence interval, CI 0.57-1.87]; p = 0.46). The median number of day-28 ventilator-free days was 0 (IQR 0-14) in the nicotine group and 0 (0-13) in the placebo group (with a difference estimate between the medians of 0 [95% CI -3-7]). Adverse events likely related to nicotine were rare (3%) and similar between the two groups.In patients having developed severe COVID-19 pneumonia requiring invasive mechanical ventilation, transdermal nicotine did not significantly reduce day-28 mortality. There is no indication to use nicotine in this situation.
Published: 2022
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37. Impact of Left Ventricular Ejection Fraction on Procedural and Long-Term Outcomes of Bifurcation Percutaneous Coronary Intervention

Author: Guglielmo Gallone, Jeehoon Kang, Francesco Bruno, Jung-Kyu Han, Ovidio De Filippo, Han-Mo Yang, Mattia Doronzo, Kyung-Woo Park, Gianluca Mittone, Hyun-Jae Kang, Radoslaw Parma, Hyeon-Cheol Gwon, Enrico Cerrato, Woo Jung Chun, Grzegorz Smolka, Seung-Ho Hur, Gerard Helft, Seung Hwan Han, Saverio Muscoli, Young Bin Song, Filippo Figini, Ki Hong Choi, Giacomo Boccuzzi, Soon-Jun Hong, Daniela Trabattoni, Chang-Wook Nam, Massimo Giammaria, Hyo-Soo Kim, Federico Conrotto, Javier Escaned, Carlo Di Mario, Fabrizio D'Ascenzo, Bon-Kwon Koo, Gaetano Maria de Ferrari, Università degli studi di Torino = University of Turin (UNITO), Seoul National University Hospital, Medical University of Silesia (SUM), Samsung Medical Center Sungkyunkwan University School of Medicine, Institute Division of Hematology/Oncology, Ospedale di Rivoli [Rivoli, Italy] (OR), Keimyung University, 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), Gachon University Gil Medical Center [Incheon, Republic of Korea], University of Rome 'Tor Vergeta', Università degli Studi di Roma Tor Vergata [Roma], Clinica Pederzoli [Peschiera del Garda, Italy] (CP), Ospedale S.Giovanni Bosco, Korea University [Seoul], Monzino Cardiology Center [Milan, Italy] (M2C), Maria Vittoria Hospital [Turin], Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano = University of Milan (UNIMI)-Università degli Studi di Milano = University of Milan (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Careggi University Hospital [Florence, Italie], and Lesnik, Philippe
Subjects: [SDV] Life Sciences [q-bio], Ventricular Dysfunction, Left, Percutaneous Coronary Intervention, Treatment Outcome, [SDV]Life Sciences [q-bio], Humans, Drug-Eluting Stents, Stroke Volume, Coronary Artery Disease, Registries, Cardiology and Cardiovascular Medicine, Ventricular Function, Left, Retrospective Studies
Abstract: International audience; The association of left ventricular ejection fraction (LVEF) with procedural and long-term outcomes after state-of-the-art percutaneous coronary intervention (PCI) of bifurcation lesions remains unsettled. A total of 5,333 patients who underwent contemporary coronary bifurcation PCI were included in the intercontinental retrospective combined insights from the unified RAIN (veRy thin stents for patients with left mAIn or bifurcatioN in real life) and COBIS (COronary BIfurcation Stenting) III bifurcation registries. Of 5,003 patients (93.8%) with known baseline LVEF, 244 (4.9%) had LVEF
Published: 2022
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38. Clonotypic IgH Response against Systemic Viral infection in Pronephros and Spleen of a Teleost Fish

Author: Rosario Castro, Susana Magadán, Luc Jouneau, Vanessa Mhana, Hang-Phuong Pham, Encarnita Mariotti-Ferrandiz, Adrien Six, François Huetz, Pierre Boudinot, Virologie et Immunologie Moléculaires (VIM (UR 0892)), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Vigo [ Pontevedra], Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and ANR-16-CE20-0002,Fish-RNAvax,Vaccins ARN éco-compatibles pour l'induction de réponses immunitaires protectrices chez le poisson d'élevage(2016)
Subjects: [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, MESH: Spleen, fish disease, Immunology, MESH: Novirhabdoviruse, MESH: Hemorrhagic Septicemia, Viral, Pronephros, Novirhabdovirus, Fish Diseases, viral hemorrhagic septicemia, MESH: Oncorhynchus mykiss, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, MESH: Fish Diseasess, Virus Diseases, MESH: Pronephros, Oncorhynchus mykiss, virus infection, Hemorrhagic Septicemia, Viral, Animals, Immunology and Allergy, animal, genetics, MESH: Animals, MESH: Virus Diseas, Spleen
Abstract: Upon infection, B lymphocytes develop clonal responses. In teleost fish, which lack lymph nodes, the kinetics and location of B cell responses remain poorly characterized. Fish pronephros is the site of B cell differentiation and the main niche for persistence of plasma cells. In this study, we undertook the analysis of the rainbow trout IgHμ repertoire in this critical tissue for humoral adaptive immunity after primary immunization and boost with a rhabdovirus, the viral hemorrhagic septicemia virus (VHSV). We used a barcoded 5′ RACE-cDNA sequencing approach to characterize modifications of the IgHμ repertoire, including VH usage in expressed V(D)J rearrangements, clonal diversity, and clonotype sharing between individual fish and treatments. In the pronephros, our approach quantified the clonotype frequency across the whole IgH repertoire (i.e., with all VH), measuring the frequency of Ag-responding clonotypes. Viral infection led to extensive modifications of the pronephros B cell repertoire, implicating several VH subgroups after primary infection. In contrast, only modest changes in repertoire persisted 5 mo later, including VHSV-specific public expansions. The IgM public response implicating IgHV1-18 and JH5, previously described in spleen, was confirmed in pronephros in all infected fish, strongly correlated to the response. However, the distribution of top clonotypes showed that pronephros and spleen B cells constitute distinct compartments with different IgH repertoires. Unexpectedly, after boost, the frequency of anti-VHSV clonotypes decreased both in pronephros and spleen, raising questions about B cell circulation. A better monitoring of B cell response kinetics in lymphoid tissues will be an essential step to understand B memory and plasmocyte formation mechanisms in fish.
Published: 2022
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39. Role of insulin resistance on fertility – Focus on polycystic ovary syndrome

Author: Camille Vatier, Sophie Christin-Maitre, Corinne Vigouroux, Centre National de Référence des Pathologies Rares de l'Insulino-Sécrétion et de l'Insulino-Sensibilité [CHu Saint-Antoine] (PRISIS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de référence des maladies endocriniennes rares de la croissance et du développement [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Service d'Endocrinologie, diabétologie et endocrinologie de la reproduction [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN)
Subjects: Inulinorésistance, Metabolic Syndrome, Infertilité, Endocrinology, Diabetes and Metabolism, polycystic ovaries, Ovaires polykystiques, General Medicine, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Fertility, Endocrinology, Adipokines, Infertility, Humans, Insulin, Female, Obesity, Insulin Resistance, Polycystic Ovary Syndrome
Abstract: International audience; Several lines of evidence show that gonadal functions and insulin sensitivity display multifaceted relationships, which extend far beyond the well-known association between polycystic ovary syndrome (PCOS), obesity, and metabolic syndrome. In this brief review, we will summarize the main findings showing the pathophysiological role of insulin resistance in impairing reproductive functions. Extreme phenotypes of severe insulin resistance, due to primary defects in insulin receptor or to lipodystrophy syndromes, provide unique opportunities for the modeling of interactions between insulin signaling and ovarian endocrine functions. In addition, recent studies further suggest that common forms of dysfunctional adiposity, as well as altered production of adipokines, could underlie important pathophysiological links between metabolic syndrome and infertility.; De multiples relations existent entre les fonctions gonadiques et la sensibilité à l’insuline, allant bien au-delà de l’association bien connue entre le syndrome des ovaires polykystiques (SOPK), l’obésité et le syndrome métabolique. Dans cette revue, nous résumerons les principales découvertes montrant le rôle physiopathologique de l’insulino-résistance dans l’altération des fonctions reproductives. Les phénotypes extrêmes d’insulino-résistance sévère, dus à des altérations du récepteur de l’insuline ou à des syndromes lipodystrophiques, offrent des opportunités uniques pour la modélisation des interactions entre la signalisation de l’insuline et les fonctions ovariennes endocrines. En outre, des études récentes suggèrent que les formes communes de dysfonction adipocytaire et/ou d’altération de la production d’adipokines, pourraient être à l’origine de liens physiopathologiques importants entre le syndrome métabolique et l’infertilité.
Published: 2022
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40. Comparison of 8 versus 15 days of antibiotic therapy for Pseudomonas aeruginosa ventilator-associated pneumonia in adults: a randomized, controlled, open-label trial

Author: Adrien, Bouglé, Sophie, Tuffet, Laura, Federici, Marc, Leone, Antoine, Monsel, Thomas, Dessalle, Julien, Amour, Claire, Dahyot-Fizelier, François, Barbier, Charles-Edouard, Luyt, Olivier, Langeron, Bernard, Cholley, Julien, Pottecher, Tarik, Hissem, Jean-Yves, Lefrant, Benoit, Veber, Matthieu, Legrand, Alexandre, Demoule, Pierre, Kalfon, Jean-Michel, Constantin, Alexandra, Rousseau, Tabassome, Simon, Arnaud, Foucrier, Nora, Soussi, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Sud Francilien, Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre d'investigation clinique Biothérapie [CHU Pitié-Salpêtrière] (CIC-BTi), 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), Pharmacologie des anti-infectieux et antibiorésistance (PHAR2), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Régional d'Orléans (CHRO), 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), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), CHU Strasbourg, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Initial MAnagement and prevention of acute orGan failures IN critically ill patiEnts (IMAGINE), Université de Montpellier (UM), CHU Rouen, Normandie Université (NU), Hôpital Lariboisière-Fernand-Widal [APHP], Hôpital Louis Pasteur [Chartres], CHU Clermont-Ferrand, Centre de Ressources Biologiques APHP-SU (PASS-CRB-APHP-SU), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), 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), and Hôpital Beaujon [AP-HP]
Subjects: Adult, MESH: Humans, Survival, Pneumonia, Ventilator-Associated, MESH: Adult, MESH: Pneumonia, Ventilator-Associated, Antibiotic therapy, Critical Care and Intensive Care Medicine, Respiration, Artificial, Anti-Bacterial Agents, Ventilator-associated pneumonia, Intensive Care Units, Recurrence, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Anti-Bacterial Agents, MESH: Intensive Cate Units, MESH: Pseudomonas aeruginosa, Pseudomonas aeruginosa, Humans, MESH: Respiration, Artificial
Abstract: International audience; Purpose: Duration of antibiotic therapy for ventilator-associated pneumonia (VAP) due to non-fermenting Gram-negative bacilli (NF-GNB), including Pseudomonas aeruginosa (PA) remains uncertain. We aimed to assess the non-inferiority of a short duration of antibiotics (8 days) vs. prolonged antibiotic therapy (15 days) in VAP due to PA (PA-VAP).Methods: We conducted a nationwide, randomized, open-labeled, multicenter, non-inferiority trial to evaluate optimal duration of antibiotic treatment in PA-VAP. Eligible patients were adults with diagnosis of PA-VAP and randomly assigned in 1:1 ratio to receive a short-duration treatment (8 days) or a long-duration treatment (15 days). A pre-specified analysis was used to assess a composite endpoint combining mortality and PA-VAP recurrence rate during hospitalization in the intensive care unit (ICU) within 90 days.Results: The study was stopped after 24 months due to slow inclusion rate. In intention-to-treat population (n = 186), the percentage of patients who reached the composite endpoint was 25.5% (N = 25/98) in the 15-day group versus 35.2% (N = 31/88) in the 8-day group (difference 9.7%, 90% confidence interval (CI) -1.9%-21.2%). The percentage of recurrence of PA-VAP during the ICU stay was 9.2% in the 15-day group versus 17% in the 8-day group. The two groups had similar median days of mechanical ventilation, of ICU stay, number of extra pulmonary infections and acquisition of multidrug-resistant (MDR) pathogens during ICU stay.Conclusions: Our study failed to show the non-inferiority of a short duration of antibiotics in the treatment of PA-VAP, compared to a long duration. The short duration strategy may be associated to an increase of PA-VAP recurrence. However, the lack of power limits the interpretation of this study.
Published: 2022
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41. Therapeutic indications and metabolic effects of metreleptin in patients with lipodystrophy syndromes: Real‐life experience from a national reference network

Author: Héléna Mosbah, Marie‐Christine Vantyghem, Estelle Nobécourt, Fabrizio Andreelli, Francoise Archambeaud, Elise Bismuth, Claire Briet, Maryse Cartigny, Benjamin Chevalier, Bruno Donadille, Anne Daguenel, Mathilde Fichet, Jean‐François Gautier, Sonja Janmaat, Isabelle Jéru, Carole Legagneur, Lysiane Leguier, Julie Maitre, Elise Mongeois, Christine Poitou, Eric Renard, Yves Reznik, Anne Spiteri, Florence Travert, Bruno Vergès, Jamila Zammouri, Corinne Vigouroux, Camille Vatier, Recherche translationnelle sur le diabète - U 1190 (RTD), 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), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Centre de Recherche Saint-Antoine (CRSA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: Adult, Leptin, Adolescent, Lipodystrophy, Endocrinology, Diabetes and Metabolism, Syndrome, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Middle Aged, Young Adult, Endocrinology, Lipodystrophy, Congenital Generalized, Internal Medicine, Humans, Retrospective Studies
Abstract: International audience; Aims: To describe baseline characteristics and follow-up data in patients with lipodystrophy syndromestreated with metreleptin in a national reference network, in a real-life setting.Patients and Methods: Clinical and metabolic data from patients receiving metreleptin in France wereretrospectively collected, at baseline, one year and at the latest follow-up during treatment.Results: Forty-seven patients with lipodystrophy including generalized lipodystrophy (GLD, n=28) andpartial lipodystrophy (PLD, n=19) received metreleptin over the last decade. At baseline, age was 29.3[16.6-47.6] (years, median [interquartile range]); BMI 23.8 kg/m2 [21.2-25.7]; serum leptin 3.2 [1.0-4.9] ng/mL); 94% of patients had diabetes (66% insulin-treated), 53% hypertension, and 87%dyslipidemia. Metreleptin therapy, administered during 31.7 [14.2-76.0] months, was ongoing in 77%of patients at the latest follow-up. In patients with GLD, HbA1c (%) and fasting triglycerides (mmol/L)significantly decreased from baseline to one year-metreleptin treatment, from 8.4 [6.5-9.9] to 6.8 [5.6-7.4], and 3.6 [1.7-8.5] to 2.2 [1.1-3.7] respectively (p
Published: 2022
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42. Iron deficiency screening is a key issue in chronic inflammatory diseases: A call to action

Author: Patrice Cacoub, Gabriel Choukroun, Alain Cohen‐Solal, Elisabeth Luporsi, Laurent Peyrin‐Biroulet, Katell Peoc'h, Valérie Andrieu, Sigismond Lasocki, Hervé Puy, Jean‐Noël Trochu, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), 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), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), 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)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Hôpital de Mercy, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Beaujon [AP-HP], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université d'Angers (UA), Hôpital Louis Mourier - AP-HP [Colombes], Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, and Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)
Subjects: Iron, Anemia, iron deficiency, Hepcidins, transferrin saturation, Internal Medicine, cancer, Humans, Anemia, Iron-Deficiency, Hepcidins/therapeutic use, Transferrins/therapeutic use, Iron/therapeutic use, serum ferritin, Iron Deficiencies, chronic inflammatory disease, chronic heart failure, Iron-Deficiency/diagnosis/etiology, Chronic Disease, Ferritins, Quality of Life, Transferrins, Cytokines, bowel inflammatory disease, Biomarkers, chronic kidney disease, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Iron deficiency is frequent in patients with chronic inflammatory conditions (e.g., chronic heart failure, chronic kidney disease, cancers, and bowel inflammatory diseases). Indeed, high concentrations of inflammatory cytokines increase hepcidin concentrations that lead to the sequestration of iron in cells of the reticuloendothelial system (functional iron deficiency). Iron parameters are often assessed only in the context of anemia, but iron deficiency, even without anemia, is present in about half of patients with inflammatory conditions. Iron deficiency worsens underlying chronic diseases and is an independent factor of morbidity and mortality. In daily practice, the most effective biomarkers of iron status are serum ferritin, which reflects iron storage, and transferrin saturation, which reflects the transport of iron. Serum ferritin is increased in an inflammatory context, and there is still no consensus on the threshold to be used in chronic inflammatory conditions. Nevertheless, recent recommendations of international guidelines agreed to define iron deficiency by serum ferritin
Published: 2022
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43. Cerebrovascular Ischemic Events in Patients With Takayasu Arteritis

Author: Adrien, Mirouse, Sandrine, Deltour, Delphine, Leclercq, Pierre-Alexandre, Squara, Clara, Pouchelon, Cloé, Comarmond, Jean-Emmanuel, Kahn, Ygal, Benhamou, Tristan, Mirault, Arsène, Mekinian, Marc, Lambert, Laurent, Chiche, Fabien, Koskas, Philippe, Cluzel, Alban, Redheuil, Patrice, Cacoub, Lucie, Biard, David, Saadoun, CACOUB, Patrice, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [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], 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), Hopital Saint-Louis [AP-HP] (AP-HP), Épidémiologie et statistiques cliniques pour les évaluations tumorales, respiratoires et de réanimation (ECSTRRA), Centre of Research in Epidemiology and StatisticS (CRESS), Hôpital Lariboisière-Fernand-Widal [APHP], Hôpital Ambroise Paré [AP-HP], CHU Rouen, Normandie Université (NU), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Saint-Antoine [AP-HP], and CHU Lille
Subjects: Male, Advanced and Specialized Nursing, [SDV.IMM] Life Sciences [q-bio]/Immunology, Aspirin, Constriction, Pathologic, Takayasu Arteritis, vasculitis, United States, Stroke, transient, Ischemic Attack, Transient, middle aged, arteritis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Humans, Female, cardiovascular diseases, Neurology (clinical), ischemic attack, Cardiology and Cardiovascular Medicine
Abstract: Background: Takayasu arteritis (TA) is a large vessel vasculitis that may complicate with cerebrovascular ischemic events. The objective was to describe clinical and vascular features of TA patients with cerebrovascular ischemic events and to identify risk factors for these events. Methods: We analyzed the prevalence and type of stroke/transient ischemic attack (TIA), factors associated with cerebrovascular ischemic events, and stroke-free survival in a large cohort fulfilling the American College of Rheumatology or Ishikawa criteria of TA. Results: Among 320 patients with TA (median age at diagnosis, 36 [25–47] years; 261 [86%] women), 63 (20%) had a stroke (n=41; 65%) or TIA (n=22; 35%). Ischemic event localized in the carotid territory for 55 (87%) patients and the vertebral artery territory in 8 (13%) patients. Multiple stenosis were observed in 33 (52%) patients with a median number of stenosis of 2 (minimum, 0 to maximum, 11), and aneurysms were observed in 10 (16%) patients. A history of stroke or TIA before TA diagnosis (hazard ratio [HR], 4.50 [2.45–8.17]; P P =0.05), myocardial infarction history (HR, 0.21 [0.05–0.89]; P =0.039), thoracic aorta involvement (HR, 2.05 [1.30–3.75]; P =0.023), time from first symptoms to diagnosis >1 year (HR, 2.22 [1.30–3.80]; P =0.005), and aspirin treatment (HR, 1.82 [1.04–3.19]; P =0.035) were associated with cerebrovascular ischemic event. In multivariate analysis, time from first symptoms to TA diagnosis >1 year (HR, 2.16 [1.27–3.70]; P =0.007) was independently associated with cerebrovascular ischemic events in patients with TA. The HR for cerebrovascular ischemic event in patients who already experienced a stroke/TIA was 5.11 (2.91–8.99; P Conclusions: Carotid stroke/TIA is frequent in TA. We identified factors associated with cerebrovascular ischemic events.
Published: 2022
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44. Intensive chemotherapy followed by autologous stem cell transplantation in primary central nervous system lymphomas (PCNSLs). Therapeutic outcomes in real life—experience of the French Network

Author: Schenone, Laurence, Houillier, Caroline, Tanguy, Marie Laure, Choquet, Sylvain, Agbetiafa, Kossi, Ghesquières, Hervé, Damaj, Gandhi, Schmitt, Anna, Bouabdallah, Krimo, Ahle, Guido, Gressin, Remy, Cornillon, Jérôme, Houot, Roch, Marolleau, Jean-Pierre, Fornecker, Luc-Matthieu, Chinot, Olivier, Peyrade, Frédéric, Bouabdallah, Reda, Moluçon-Chabrot, Cécile, Gyan, Emmanuel, Chauchet, Adrien, Casasnovas, Olivier, Oberic, Lucie, Delwail, Vincent, Abraham, Julie, Roland, Virginie, Waultier-Rascalou, Agathe, Willems, Lise, Morschhauser, Franck, Fabbro, Michel, Ursu, Renata, Thieblemont, Catherine, Jardin, Fabrice, Tempescul, Adrian, Malaise, Denis, Touitou, Valérie, Nichelli, Lucia, Le Garff-Tavernier, Magali, Plessier, Aurélie, Bourget, Philippe, Bonmati, Caroline, Wantz-Mézières, Sophie, Giordan, Quentin, Dorvaux, Véronique, Charron, Cyril, Jabeur, Waliyde, Hoang-Xuan, Khê, Taillandier, Luc, Soussain, Carole, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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), Institut Gustave Roussy (IGR), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département d'hématologie, Institut Curie, Site Saint-Cloud, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Bergonié [Bordeaux], UNICANCER, CHU Bordeaux [Bordeaux], Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Centre Hospitalier Universitaire [Grenoble] (CHU), Institut de Cancérologie Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-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 ), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Strasbourg, Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Dupuytren [CHU Limoges], Centre Hospitalier Saint Jean de Perpignan, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut du Cancer de Montpellier (ICM), Hopital Saint-Louis [AP-HP] (AP-HP), NF-kappaB, Différenciation et Cancer (OncokappaB (URP_7324)), Université Paris Cité (UPCité), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Département d'Oncologie Chirurgicale [Institut Curie], Institut Curie [Paris], Laboratoire d'Imagerie Translationnelle en Oncologie (LITO ), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Beaujon [AP-HP], CHU Necker - Enfants Malades [AP-HP], Biology, genetics and statistics (BIGS), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Élie Cartan de Lorraine (IECL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut Élie Cartan de Lorraine (IECL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Hôpital de Mercy, Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Hôpital Ambroise Paré [AP-HP], Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de Recherche en Automatique de Nancy (CRAN), Institut Curie - Saint Cloud (ICSC), Immunité et cancer (U932), and We thank the clinicians involved in the French National 'Lymphome Oculo-Cérébral' LOC network, part of the network for rare cancers of the central nervous system, 'RENOCLIP-LOC Network', approved by the French National Institute of Cancer (INCa).
Subjects: Transplantation, Hematology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; We analysed the therapeutic outcomes of all consecutive patients with primary central nervous system lymphoma (PCNSL) registered in the prospective French database for PCNSL and treated with intensive chemotherapy (IC) followed by autologous stem cell transplantation (IC-ASCT) between 2011 and November 2019 (271 patients recruited, 266 analysed). In addition, treatment-related complications of thiotepa-based IC-ASCT were analysed from the source files of 85 patients from 3 centers. Patients had received IC-ASCT either in first-line treatment (n\,=\,147) or at relapse (n\,=\,119). The median age at IC-ASCT was 57 years (range: 22-74). IC consisted of thiotepa-BCNU (n\,=\,64), thiotepa-busulfan (n\,=\,24), BCNU-etoposide-cytarabine-melphalan (BEAM, n\,=\,36) and thiotepa-busulfan-cyclophosphamide (n\,=\,142). In multivariate analysis, BEAM and ASCT beyond the first relapse were adverse prognostic factors for relapse risk. The risk of treatment-related mortality was higher for ASCT performed beyond the first relapse and seemed higher for thiotepa-busulfan-cyclophosphamide. Thiotepa-BCNU tends to result in a higher relapse rate than thiotepa-busulfan-cyclophosphamide and thiotepa-busulfan. This study confirms the role of IC-ASCT in first-line treatment and at first-relapse PCNSL (5-year overall survival rates of 80 and 50%, respectively). The benefit/risk ratio of thiotepa-busulfan/thiotepa-busulfan-cyclophosphamide-ASCT could be improved by considering ASCT earlier in the course of the disease and dose adjustment of the IC.
Published: 2022
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45. Development and validation of a self-administered questionnaire measuring essential knowledge in patients with rheumatoid arthritis

Author: Malory Rodère, Bruno Pereira, Martin Soubrier, Françoise Fayet, Muriel Piperno, Béatrice Pallot-Prades, Sophie Pouplin, Guy Baudens, Jean-David Cohen, Pascal Coquerelle, Laurent Grange, Christelle Sordet, Sonia Tropé, Laure Gossec, Catherine Beauvais, Service de Rhumatologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, CHU Clermont-Ferrand, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de Rhumatologie [Saint-Etienne], CHU Saint-Etienne-Hôpital de Bellevue, Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier de Béthune (CH Béthune), GHT de l'Artois, CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Les Hôpitaux Universitaires de Strasbourg (HUS), Association Nationale de Défense contre l'Arthrite Rhumatoide (ANDAR), Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Sorbonne Université (SU), and Gestionnaire, Hal Sorbonne Université
Subjects: Male, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SHS.EDU]Humanities and Social Sciences/Education, [SHS.EDU] Humanities and Social Sciences/Education, Immunology, Reproducibility of Results, Patient education, Patient therapeutic education, Knowledge questionnaire, Arthritis, Rheumatoid, Self Care, Cross-Sectional Studies, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Rheumatology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Surveys and Questionnaires, Humans, Immunology and Allergy, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Educational needs, Rheumatoid arthritis
Abstract: International audience; To develop and validate a questionnaire assessing patient knowledge in rheumatoid arthritis (RA). Knowledge considered essential for patients with RA was identified through a series of Delphi rounds among rheumatologists, health professionals (HPs), patients, and then reformulated to construct the knowledge questionnaire. Cross-sectional multicenter validation was performed in 12 rheumatology departments to assess internal validity (Kuder\textendash Richardson coefficient), external validity, acceptability, reproducibility (Lin's concordance correlation coefficient) and sensitivity to change (difference in total score before and after patient education sessions). Associations between patient variables and knowledge levels were evaluated. RAKE (RA Knowledge questionnairE) is a self-administered 45-item questionnaire scored 0\textendash 100, with a 32-item short-form survey assessing knowledge of disease, comorbidity, pharmacological treatments, non-pharmacological treatments, self-care and adaptative skills. Of 130 patients included in the validation study, 108 were women. Acceptability was good with\
Published: 2022
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46. Efficacy of Caffeine in <scp>ADCY5</scp> ‐Related Dyskinesia: A Retrospective Study

Author: Aurélie Méneret, Shekeeb S. Mohammad, Laura Cif, Diane Doummar, Claudio DeGusmao, Mathieu Anheim, Magalie Barth, Philippe Damier, Nathalie Demonceau, Jennifer Friedman, Cécile Gallea, Domitille Gras, Juliana Gurgel‐Giannetti, Emily A. Innes, Ján Necpál, Florence Riant, Sandrine Sagnes, Catherine Sarret, Yury Seliverstov, Vijayashankar Paramanandam, Kuldeep Shetty, Christine Tranchant, Mohamed Doulazmi, Marie Vidailhet, Tamara Pringsheim, Emmanuel Roze, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), 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), University of California [San Diego] (UC San Diego), University of California (UC), AP-HP Hôpital universitaire Robert-Debré [Paris], Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Observatoire National Français des patients atteints de DMFSH (FSHD registry - France), Institut de Biologie Paris Seine (IBPS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Dyskinesias, Movement Disorders, Neurology, Caffeine, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Humans, Neurology (clinical), Child, Adenylyl Cyclases, Retrospective Studies
Abstract: ADCY5-related dyskinesia is characterized by early-onset movement disorders. There is currently no validated treatment, but anecdotal clinical reports and biological hypotheses suggest efficacy of caffeine.The aim is to obtain further insight into the efficacy and safety of caffeine in patients with ADCY5-related dyskinesia.A retrospective study was conducted worldwide in 30 patients with a proven ADCY5 mutation who had tried or were taking caffeine for dyskinesia. Disease characteristics and treatment responses were assessed through a questionnaire.Caffeine was overall well tolerated, even in children, and 87% of patients reported a clear improvement. Caffeine reduced the frequency and duration of paroxysmal movement disorders but also improved baseline movement disorders and some other motor and nonmotor features, with consistent quality-of-life improvement. Three patients reported worsening.Our findings suggest that caffeine should be considered as a first-line therapeutic option in ADCY5-related dyskinesia. © 2022 International Parkinson and Movement Disorder Society.
Published: 2022
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47. Mise à jour des croyances et congruence à l'humeur dans le trouble dépressif

Author: BOTTEMANNE, Hugo, Frileux, S., Guesdon, A., Fossati, P., Service de Psychiatrie Adulte [CHU Pitié-Salpêtière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de médecine [CHU Pitié Salpétrière], Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sciences, Normes, Démocratie [Paris] (SND), and Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Psychiatry and Mental health, Arts and Humanities (miscellaneous), [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.PSYC]Cognitive science/Psychology, [SHS.PHIL]Humanities and Social Sciences/Philosophy, [SHS.PSY]Humanities and Social Sciences/Psychology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2022
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48. Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis

Author: Lin Lei, Alix Bruneau, Haquima El Mourabit, Justine Guégan, Trine Folseraas, Sara Lemoinne, Tom Hemming Karlsen, Bénédicte Hoareau, Romain Morichon, Ester Gonzalez‐Sanchez, Claire Goumard, Vlad Ratziu, Pierre Charbord, Jérémie Gautheron, Frank Tacke, Thierry Jaffredo, Axelle Cadoret, Chantal Housset, Centre de Recherche Saint-Antoine (CRSA), 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), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], 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), Plateforme iCONICS [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Oslo University Hospital [Oslo], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Cytométrie Pitié-Salpêtrière (PASS-CYPS), 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), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Cadoret, Axelle
Subjects: Single-cell RNA-sequencing, Liver Cirrhosis, Hepatology, Liver Diseases, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Mesenchymal Stem Cells, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Fibroblasts, Ligands, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Mice, Cirrhosis, Liver, Culture Media, Conditioned, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Hepatic Stellate Cells, Humans, Animals, RNA, Perivascular, Myofibroblasts, In Situ Hybridization, Fluorescence, Cells, Cultured
Abstract: International audience; Background and Aims: In liver fibrosis, myofibroblasts derive from HSCs and as yet undefined mesenchymal cells. We aimed to identify portal mesenchymal progenitors of myofibroblasts.Approach and Results: Portal mesenchymal cells were isolated from mouse bilio-vascular tree and analyzed by single-cell RNA-sequencing. Thereby, we uncovered the landscape of portal mesenchymal cells in homeostatic mouse liver. Trajectory analysis enabled inferring a small cell population further defined by surface markers used to isolate it. This population consisted of portal fibroblasts with mesenchymal stem cell features (PMSCs), i.e., high clonogenicity and trilineage differentiation potential, that generated proliferative myofibroblasts, contrasting with nonproliferative HSC-derived myofibroblasts (-MF). Using bulk RNA-sequencing, we built oligogene signatures of the two cell populations that remained discriminant across myofibroblastic differentiation. SLIT2, a prototypical gene of PMSC/PMSC-MF signature, mediated profibrotic and angiogenic effects of these cells, which conditioned medium promoted HSC survival and endothelial cell tubulogenesis. Using PMSC/PMSC-MF 7-gene signature and slit guidance ligand 2 fluorescent in situ hybridization, we showed that PMSCs display a perivascular portal distribution in homeostatic liver and largely expand with fibrosis progression, contributing to the myofibroblast populations that form fibrotic septa, preferentially along neovessels, in murine and human liver disorders, irrespective of etiology. We also unraveled a 6-gene expression signature of HSCs/HSC-MFs that did not vary in these disorders, consistent with their low proliferation rate.Conclusions: PMSCs form a small reservoir of expansive myofibroblasts, which, in interaction with neovessels and HSC-MFs that mainly arise through differentiation from a preexisting pool, underlie the formation of fibrotic septa in all types of liver diseases
Published: 2022
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49. Antithrombotic therapies for neurointerventional surgery: a 2021 French comprehensive national survey

Author: Jildaz, Caroff, Laurent, Aubert, Cécile, Lavenu-Bombled, Samy, Figueiredo, Kamelia, Habchi, Jonathan, Cortese, Francois, Eugene, Julien, Ognard, Florence, Tahon, Géraud, Forestier, Heloise, Ifergan, François, Zhu, Jean-Francois, Hak, Anthony, Reyre, Morgane, Laubacher, Abdoulaye, Traore, Jean Philippe, Desilles, Imad, Derraz, Ricardo, Moreno, Marc, Bintner, Guillaume, Charbonnier, Anthony, Le Bras, Louis, Veunac, Florent, Gariel, Hocine, Redjem, Jacques, Sedat, Guillaume, Tessier, Victor, Dumas, Maxime, Gauberti, Cyril, Chivot, Arturo, Consoli, Nicolas, Bricout, Titien, Tuilier, Alexis, Guedon, Raoul, Pop, Pierre, Thouant, Guillaume, Bellanger, Riccardo, Zannoni, Sebastien, Soize, Johann Sebastian, Richter, Olivier, Heck, Cristian, Mihalea, Julien, Burel, Jean-Baptiste, Girot, Eimad, Shotar, Sebastian, Gazzola, Gregoire, Boulouis, Basile, Kerleroux, Laurent, Spelle, Service de Neuroradiologie [CHU de Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de Neuroradiologie [Rennes], CHU Pontchaillou [Rennes], CHRU Brest - Service d'Imagerie médicale (CHU - Brest - HM), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Optimisation Continue des Actions Thérapeutiques par l'Intégration d'Informations Multimodales, Université de Brest (UBO)-Télécom Bretagne-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Privé Clairval [Marseille], CHU Limoges, Service de neuroradiologie [Tours], Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hospices Civils de Lyon (HCL), Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Fondation Ophtalmologique Adolphe de Rothschild [Paris], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Clermont-Ferrand, Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Service de Neuroradiologie Interventionnelle [CHU Besançon], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Le CHCB, Centre Hospitalier de la Côte Basque, CHU de Bordeaux Pellegrin [Bordeaux], Clinique des Cèdres, Centre Hospitalier Universitaire de Nice (CHU Nice), Département de Neuroradiologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Amiens-Picardie, Service Neuroradiologie diagnostique et interventionnelle [Hôpital Foch], Hôpital Foch [Suresnes], CHU Lille, CHU Henri Mondor, Hôpital Lariboisière-Fernand-Widal [APHP], CHU Strasbourg, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Toulouse [Toulouse], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre hospitalier de Pau, Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Rouen, Normandie Université (NU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Saint Anne Military Teaching Hospital [Toulon, France], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and Centre Hospitalier Saint-Anne (GHU Paris)
Subjects: Surgery, Neurology (clinical), General Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: BackgroundNeurointerventionists lack guidelines for the use of antithrombotic therapies in their clinical practice; consequently, there is likely to be significant heterogeneity in antithrombotic use between centers. Through a nationwide survey, we aimed to obtain an exhaustive cross-sectional overview of antithrombotic use in neurointerventional procedures in France.MethodsIn April 2021, French neurointerventional surgery centers were invited to participate in a nationwide 51-question survey disseminated through an active trainee-led research collaborative network (the JENI-RC).ResultsAll 40 centers answered the survey. Fifty-one percent of centers reported using ticagrelor and 43% used clopidogrel as premedication before intracranial stenting. For flow diversion treatment, dual antiplatelet therapy was maintained for 3 or 6 months in 39% and 53% of centers, respectively, and aspirin was prescribed for 12 months or more than 12 months in 63% and 26% of centers, respectively. For unruptured aneurysms, the most common heparin bolus dose was 50 IU/kg (59%), and only 35% of centers monitored heparin activity for dose adjustment. Tirofiban was used in 64% of centers to treat thromboembolic complications. Fifteen percent of these comprehensive stroke centers reported using tenecteplase to treat acute ischemic strokes. Cangrelor appeared as an emergent drug in specific indications.ConclusionThis nationwide survey highlights the important heterogeneity in clinical practices across centers. There is a pressing need for trials and guidelines to further evaluate and harmonize antithrombotic regimens in the neurointerventional field.
Published: 2022
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50. The European MAPPYACTS Trial: Precision Medicine Program in Pediatric and Adolescent Patients with Recurrent Malignancies

Author: Pablo Berlanga, Gaelle Pierron, Ludovic Lacroix, Mathieu Chicard, Tiphaine Adam de Beaumais, Antonin Marchais, Anne C. Harttrampf, Yasmine Iddir, Alicia Larive, Aroa Soriano Fernandez, Imene Hezam, Cecile Chevassus, Virginie Bernard, Sophie Cotteret, Jean-Yves Scoazec, Arnaud Gauthier, Samuel Abbou, Nadege Corradini, Nicolas André, Isabelle Aerts, Estelle Thebaud, Michela Casanova, Cormac Owens, Raquel Hladun-Alvaro, Stefan Michiels, Olivier Delattre, Gilles Vassal, Gudrun Schleiermacher, Birgit Geoerger, Institut Català de la Salut, [Berlanga P] Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France. [Pierron G] Unité de Génétique Somatique, Service de Génétique, Hospital Group, Institut Curie, Paris, France. [Lacroix L] Department of Pathology and Laboratory Medicine, Translational Research Laboratory and Biobank, AMMICA, INSERM US23/CNRS UMS3655, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France. [Chicard M] INSERM U830, Laboratoire de Génétique et Biologie des Cancers, Research Center, PSL Research University, Institut Curie, Paris, France. [Adam de Beaumais T] Clinical Research Direction, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France. [Marchais A] INSERM U1015, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France. [Soriano Fernandez A] Grup de Recerca Translacional en Càncer en la Infància i l’Adolescència, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Hladun-Alvaro R] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei d’Oncologia i Hematologia Pediàtriques, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Institut Gustave Roussy (IGR), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Curie [Paris], Department of Medical Oncology, Département de médecine oncologique [Gustave Roussy], Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme de Bioinformatique [Gustave Roussy], Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunologie anti-tumorale et immunothérapie des cancers (ITIC), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, 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), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre de Recherche et de Documentation sur l'Océanie (CREDO), École des hautes études en sciences sociales (EHESS)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique [Châtenay-Malabry] (LabEx LERMIT), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de biologie et pathologie médicales [Gustave Roussy], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Prédicteurs moléculaires et nouvelles cibles en oncologie (PMNCO), Centre Léon Bérard [Lyon], Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Biologie Cellulaire et Cancer, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Nantes (CHU Nantes), Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), Oncostat (U1018 (Équipe 2)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Immunologie des tumeurs et immunothérapie (UMR 1015), Vectorologie et thérapeutiques anti-cancéreuses [Villejuif] (UMR 8203), and Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS)
Subjects: neoplasias::procesos neoplásicos::recurrencia neoplásica local [ENFERMEDADES], Pediatria, Adolescent, [SDV]Life Sciences [q-bio], Carcinoma, High-Throughput Nucleotide Sequencing, Neoplasms [DISEASES], neoplasias [ENFERMEDADES], Càncer - Recaiguda, terapéutica::medicina de precisión [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Oncology, Mutation, Biomarkers, Tumor, Neoplasms::Neoplastic Processes::Neoplasm Recurrence, Local [DISEASES], Humans, Prospective Studies, Medicina personalitzada, Neoplasm Recurrence, Local, Precision Medicine, Child, Therapeutics::Precision Medicine [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Cell-Free Nucleic Acids
Abstract: Abstract MAPPYACTS (NCT02613962) is an international prospective precision medicine trial aiming to define tumor molecular profiles in pediatric patients with recurrent/refractory malignancies in order to suggest the most adapted salvage treatment. From February 2016 to July 2020, 787 patients were included in France, Italy, Ireland, and Spain. At least one genetic alteration leading to a targeted treatment suggestion was identified in 436 patients (69%) with successful sequencing; 10% of these alterations were considered “ready for routine use.” Of 356 patients with follow-up beyond 12 months, 107 (30%) received one or more matched targeted therapies—56% of them within early clinical trials—mainly in the AcSé-ESMART platform trial (NCT02813135). Overall, matched treatment resulted in a 17% objective response rate, and of those patients with ready for routine use alterations, it was 38%. In patients with extracerebral tumors, 76% of actionable alterations detected in tumor tissue were also identified in circulating cell-free DNA (cfDNA). Significance: MAPPYACTS underlines the feasibility of molecular profiling at cancer recurrence in children on a multicenter, international level and demonstrates benefit for patients with selected key drivers. The use of cfDNA deserves validation in prospective studies. Our study highlights the need for innovative therapeutic proof-of-concept trials that address the underlying cancer complexity. This article is highlighted in the In This Issue feature, p. 1171
Published: 2022
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