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1. Brief Report:First-line Pembrolizumab in Metastatic Non-Small Cell Lung Cancer Habouring MET Exon 14 Skipping Mutation and PD-L1 ≥50% (GFPC 01-20 Study)

Author: Florian Guisier, Renaud Descourt, Helene Babey, Eric Huchot, Lionel Falchero, Remi Veillon, Alexis B. Cortot, Claire Tissot, Christos Chouaid, Chantal Decroisette, Université de Rouen Normandie [UNIROUEN], Centre d'Investigation Clinique [CHU Rouen] [CIC Rouen], Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes [LITIS], CHU Rouen, Hôpital Morvan - CHRU de Brest [CHU - BREST ], CHU Sud Saint Pierre [Ile de la Réunion], Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER], Institut de Cancérologie Lucien Neuwirth, CHI Créteil, Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Hôpital Morvan - CHRU de Brest (CHU - BREST ), L'Hôpital Nord-Ouest [Villefranche sur Saône], Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], CHU Lille, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), 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), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Pulmonary and Respiratory Medicine, MET exon 14 skipping mutation, Cancer Research, Oncology, biomarker, [SDV.CAN]Life Sciences [q-bio]/Cancer, oncogenic addiction, non-small cell lung cancer
Abstract: International audience; No abstract available
Published: 2022
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2. Sicca syndrome in systemic sclerosis: a narrative review on a neglected issue

Author: François Zimmermann, François Robin, Leila Caillault, Claire Cazalets, Francisco Llamas-Gutierrez, Ronan Garlantézec, Sandrine Jousse-Joulin, Elisabeth Diot, Sami Eric Mensi, Nicolas Belhomme, Patrick Jégo, Guillaume Coiffier, Alain Lescoat, CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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 ), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Inserm UMR 1227 Immunothérapies et Pathologies Lymphocytaires B, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and Centre hospitalier Rene Pleven de Dinan
Subjects: Rheumatology, [SDV]Life Sciences [q-bio], salivar gland biopsy, salivar gland echography, Systemic sclerosis, Pharmacology (medical), Sjogren syndrome, Sicca syndrome
Abstract: SSc is an auto-immune disease characterized by life-threatening manifestations such as lung fibrosis or pulmonary arterial hypertension. Symptoms with a detrimental impact on quality of life are also reported and sicca syndrome (xerostomia, xeropthalmia) is present in up to 80% of patients with SSc. Sicca syndrome can occur in the absence of overlap with Sjögren’s disease and recent studies highlight that fibrosis of minor and major salivary glands, directly linked to the pathogenesis of SSc, could be a major contributor of xerostomia in SSc. This narrative review provides an overview of the clinical presentation, diagnostic strategies, management and future perspectives on sicca syndrome in patients with SSc.
Published: 2022
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3. Discoidin Domain Receptor 2 orchestrates melanoma resistance combining phenotype switching and proliferation

Author: Margaux Sala, Nathalie Allain, Mélanie Moreau, Arnaud Jabouille, Elodie Henriet, Aya Abou-Hammoud, Arnaud Uguen, Sylvaine Di-Tommaso, Cyril Dourthe, Anne-Aurélie Raymond, Jean-William Dupuy, Emilie Gerard, Nathalie Dugot-Senant, Benoit Rousseau, Jean-Phillipe Merlio, Anne Pham-Ledart, Béatrice Vergier, Sophie Tartare-Deckert, Violaine Moreau, Frédéric Saltel, BoRdeaux Institute in onCology (Inserm U1312 - BRIC), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Johns Hopkins University (JHU), Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Hôpital Morvan - CHRU de Brest (CHU - BREST ), TBM-Core [Bordeaux] (CNRS UMS 3427 - INSERM US 005), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), CHU Bordeaux [Bordeaux], Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), and TARTARE-DECKERT, Sophie
Subjects: Proto-Oncogene Proteins B-raf, MESH: Proto-Oncogene Proteins B-raf, Cancer Research, MESH: Cell Line, Tumor, MESH: Humans, MESH: Melanoma, [SDV]Life Sciences [q-bio], MESH: Phenotype, MESH: Drug Resistance, Neoplasm, [SDV] Life Sciences [q-bio], Discoidin Domain Receptor 2, Phenotype, Drug Resistance, Neoplasm, Cell Line, Tumor, MESH: Cell Proliferation, MESH: Discoidin Domain Receptor 2, Genetics, Humans, MESH: Protein Kinase Inhibitors, Melanoma, Protein Kinase Inhibitors, Molecular Biology, Cell Proliferation
Abstract: International audience; Combined therapy with anti-BRAF plus anti-MEK is currently used as first-line treatment of patients with metastatic melanomas harboring the somatic BRAF V600E mutation. However, the main issue with targeted therapy is the acquisition of tumor cell resistance. In a majority of resistant melanoma cells, the resistant process consists in epithelial-to-mesenchymal transition (EMT). This process called phenotype switching makes melanoma cells more invasive. Its signature is characterized by MITF low, AXL high, and actin cytoskeleton reorganization through RhoA activation. In parallel of this phenotype switching phase, the resistant cells exhibit an anarchic cell proliferation due to hyper-activation of the MAP kinase pathway. We show that a majority of human melanoma overexpress discoidin domain receptor 2 (DDR2) after treatment. The same result was found in resistant cell lines presenting phenotype switching compared to the corresponding sensitive cell lines. We demonstrate that DDR2 inhibition induces a decrease in AXL expression and reduces stress fiber formation in resistant melanoma cell lines. In this phenotype switching context, we report that DDR2 control cell and tumor proliferation through the MAP kinase pathway in resistant cells in vitro and in vivo. Therefore, inhibition of DDR2 could be a new and promising strategy for countering this resistance mechanism.
Published: 2022
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4. Invasive bone and joint infections from the French Scedosporiosis/lomentosporiosis Observational Study (SOS) cohort: no mortality with long-term antifungal treatment and surgery

Author: Damien Blez, Didier Bronnimann, Blandine Rammaert, Valérie Zeller, Laurence Delhaes, Laurent Hustache, Frédéric Grenouillet, Nicolas Traversier, Julie Bonhomme, Taieb Chouaki, Thomas Perpoint, Florence Persat, Marie Elisabeth Bougnoux, Sophie Bayle, Luc Quaesaet, Gilles Nevez, David Boutoille, Florent Morio, Laurence Pougnet, Viviane Queyrel-Moranne, B́eate Heym, Romain Guillemain, Éric Dannaoui, Antoine Roux, Dea Garcia-Hermoso, Fanny Lanternier, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], 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), Groupe Hospitalier Diaconesses Croix Saint-Simon, INSERM U1045, IHU-LIRYC, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Amiens-Picardie, Hospices Civils de Lyon (HCL), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre Hospitalier Henri Duffaut (Avignon), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Univ - UFR Pharmacie), 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 d'Instruction des Armées 'Clermont-Tonnerre' (HIA), Hôpital Pasteur [Nice] (CHU), 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), and Hôpital Foch [Suresnes]
Subjects: Infectious Diseases, arthritis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, osteomyelitis, Lomentospora, bone infections, Scedosporium, General Medicine, scedosporiosis
Abstract: Little is known about localized osteoarticular Scedosporiosis (LOS). Most data come from case reports and small case series. Here we present an ancillary study of the nationwide French Scedosporiosis Observational Study (SOS), describing 15 consecutive cases of LOS diagnosed between January 2005 and March 2017. Adult patients diagnosed with LOS defined by osteoarticular involvement without distant foci reported in SOS were included. Fifteen LOS were analyzed. Seven patients had underlying disease. Fourteen patients had prior trauma as potential inoculation. Clinical presentation was arthritis (n = 8), osteitis (n = 5), and thoracic wall infection (n = 2). The most common clinical manifestation was pain (n = 9), followed by localized swelling (n = 7), cutaneous fistulization (n = 7), and fever (n = 5). The species involved were Scedosporium apiospermum (n = 8), S. boydii (n = 3), S. dehoogii (n = 1), and Lomentospora prolificans (n = 3). The species distribution was unremarkable except for S. boydii, which was associated with healthcare-related inoculations. Management was based on medical and surgical treatment for 13 patients. Fourteen patients received antifungal treatment for a median duration of 7 months. No patients died during follow-up. LOS exclusively occurred in the context of inoculation or systemic predisposing factors. It has a non-specific clinical presentation and is associated with an overall good clinical outcome, provided there is a prolonged course of antifungal therapy and adequate surgical management.
Published: 2023
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5. A Phase 1–2 Study of Rovalpituzumab Tesirine in Combination With Nivolumab Plus or Minus Ipilimumab in Patients With Previously Treated Extensive-Stage SCLC

Author: John Wrangle, Ticiana Leal, Gilles Robinet, Neal Ready, David Maag, Jyoti Malhotra, Melissa Lynne Johnson, Satwant Lally, Petros Nikolinakos, Jyoti D. Patel, Daniel Morgensztern, Benjamin Besse, Vincent Blot, Giuseppe Curigliano, Ricardo Valenzuela, Laurent Greillier, Jonathan M. Lehman, Rutgers cancer institute of New Jersey [Newark, NJ], University Cancer and Blood Center (UCBC), University of Wisconsin-Madison, Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Feinberg School of Medicine, Northwestern University [Evanston], Medical University of South Carolina [Charleston] (MUSC), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sarah Cannon Research Institute [Nashville, Tennessee], Duke University Medical Center, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Abbvie Inc. [North Chicago], Institut Gustave Roussy (IGR), Université Paris-Saclay, and Département de médecine oncologique [Gustave Roussy]
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Immunoconjugates, Lung Neoplasms, Combination therapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Ipilimumab, Antibodies, Monoclonal, Humanized, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Gastroenterology, MESH: Benzodiazepinones, MESH: Ipilimumab, 03 medical and health sciences, Clinical trials, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, MESH: Immunoconjugates, medicine, Humans, Antibody-drug conjugates, Adverse effect, Benzodiazepinones, MESH: Humans, business.industry, Rovalpituzumab tesirine, respiratory tract diseases, MESH: Lung Neoplasms, MESH: Antineoplastic Combined Chemotherapy Protocols, Nivolumab, 030104 developmental biology, Oncology, Tolerability, MESH: Antibodies, Monoclonal, Humanized, Response Evaluation Criteria in Solid Tumors, 030220 oncology & carcinogenesis, Cohort, Small-molecule agents, MESH: Nivolumab, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunotherapy, Lung cancer, business, medicine.drug
Abstract: Introduction This open-label, phase 1–2 study evaluated the safety and efficacy of rovalpituzumab tesirine (Rova-T), an antibody-drug conjugate targeting DLL3, plus immune checkpoint inhibitors nivolumab plus or minus ipilimumab in previously treated extensive-stage SCLC (ES SCLC). Methods Patients with histologically or cytologically confirmed, previously treated (two or more lines of therapy) ES SCLC were enrolled into two cohorts. Cohort 1 received 0.3 mg/kg Rova-T (once every 6 wk for two cycles) plus 360 mg nivolumab (two 3-wk cycles beginning on week 4). Cohort 2 received the same dosage of Rova-T as cohort 1 plus 1 mg/kg nivolumab (four 3-wk cycles) and 1 mg/kg ipilimumab (beginning week 4). Both cohorts received 480 mg nivolumab every 4 weeks starting at week 10. Key objectives were to evaluate safety and tolerability and efficacy (per Response Evaluation Criteria in Solid Tumors version 1.1). The response-related results are based on centrally read data. Results A total of 42 patients received therapy: cohort 1, n = 30; cohort 2, n = 12. Overall, 43% received two or more previous lines of therapy. All patients experienced one or more treatment-emergent adverse event (TEAE); 41 patients reported AEs considered related to the study drug by the investigator. The most frequent TEAE was pleural effusion (n = 20, 48%); most common grade greater than or equal to 3 was anemia (n = 9, 21%). Three grade 5 TEAEs considered related to the study drug were reported (cohort 1): pneumonitis (n = 2), acute kidney injury (n = 1). The objective response rate was 30% (12 of 40): cohort 1, 27.6% (8 of 29); cohort 2, 36.4% (4 of 11); all partial responses. Conclusions Despite encouraging antitumor activity in previously treated ES SCLC, combination therapy with Rova-T and nivolumab plus or minus ipilimumab was not well tolerated at the dose levels and administration schedules evaluated.
Published: 2021
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6. Effect of Tocilizumab on Disease Activity in Patients With Active Polymyalgia Rheumatica Receiving Glucocorticoid Therapy

Author: Devauchelle-Pensec, Valérie, Carvajal-Alegria, Guillermo, Dernis, Emmanuelle, Richez, Christophe, Truchetet, Marie-Elise, Wendling, Daniel, Toussirot, Eric, Perdriger, Aleth, Gottenberg, Jacques-Eric, Felten, Renaud, Fautrel, Bruno Jean, Chiche, Laurent, Hilliquin, Pascal, Le Henaff, Catherine, Dervieux, Benjamin, Direz, Guillaume, Chary-Valckenaere, Isabelle, Cornec, Divi, Guellec, Dewi, Marhadour, Thierry, Nowak, Emmanuel, Saraux, Alain, Inserm UMR 1227 Immunothérapies et Pathologies Lymphocytaires B, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Pontchaillou [Rennes], Université de Rennes (UR), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, and The funders of this study were the French National Program for Clinical Research and the study sponsor (ie, the Brest University Hospital). Roche-Chugai Pharmaceutical provided an unconditional grant for the study and donated the tocilizumab used for the study.
Subjects: MESH: Aged, MESH: Humans, MESH: Administration, Intravenous, [SDV]Life Sciences [q-bio], MESH: Giant Cell Arteritis, MESH: Interleukin-6, MESH: Male, MESH: Drug Tapering, MESH: Polymyalgia Rheumatica, MESH: Antibodies, Monoclonal, Humanized, MESH: Anti-Inflammatory Agents, MESH: Administration, Oral, MESH: C-Reactive Protein, MESH: Double-Blind Method, MESH: Glucocorticoids, MESH: Prednisone, MESH: Female
Abstract: International audience; Importance: Few treatments are available for patients with glucocorticoid-dependent polymyalgia rheumatica. IL-6 antagonists may reduce disease activity in patients with active glucocorticoid-dependent polymyalgia rheumatica.Objective: To compare the efficacy of tocilizumab vs placebo in patients with glucocorticoid-dependent polymyalgia rheumatica.Design, setting, and participants: This double-blind, parallel-group, placebo-controlled randomized clinical trial enrolled 101 patients with polymyalgia rheumatica at 17 hospitals in France from February 2017 to October 2019. Final follow-up occurred in November 2020. Inclusion criteria were persistent disease activity (polymyalgia rheumatica activity score computed using the C-reactive protein level [CRP PMR-AS] >10) and prednisone dose greater than or equal to 10 mg per day.Interventions: Patients were randomly assigned to receive intravenous tocilizumab (8 mg/kg; n = 51) or placebo (n = 50) every 4 weeks for 24 weeks, combined with predefined standardized tapering of oral prednisone.Main outcomes and measures: The primary efficacy end point was CRP PMR-AS less than 10 (range, 0-100; higher values indicate greater activity; no minimal clinically important difference defined) combined with either prednisone dose less than or equal to 5 mg per day or a decrease in prednisone dose greater than or equal to 10 mg from baseline at week 24. There were 11 secondary outcomes assessed at week 24 included in this report, including disease activity (measured by CRP PMR-AS) and the proportion of patients no longer taking prednisone.Results: Of the 101 randomized patients (mean age, 67.2 years; 68 [67.3%] women), 100 (99%) received at least 1 infusion and 100 completed the trial. The primary end point was achieved in 67.3% of patients in the tocilizumab group and 31.4% of patients in the placebo group (adjusted difference, 36.0% [95% CI, 19.4%-52.6%]; adjusted relative risk, 2.3 [95% CI, 1.5-3.6]; P < .001). Of 11 reported secondary end points at 24 weeks, 7 showed significant differences favoring tocilizumab, including mean CRP PMR-AS score (7.5 [95% CI, 5.4-9.6] vs 14.9 [95% CI, 11.4-18.4]; adjusted difference, -7.5 [95% CI, -11.2 to -3.8]; P < .001) and the percentage of patients no longer receiving prednisone (49.0% vs 19.6%; adjusted difference, 29.3% [95% CI, 18.9%-39.7%]; adjusted relative risk, 2.5 [95% CI, 1.8-3.5]; P < .001). The most frequent adverse events were infections, experienced by 23 patients (46.9%) in the tocilizumab group and 20 (39.2%) in the placebo group.Conclusions and relevance: Among patients with active polymyalgia rheumatica despite prednisone therapy, tocilizumab, compared with placebo, resulted in a significantly greater percentage of patients with a CRP PMR-AS less than 10 with reduced prednisone requirements at week 24. Further research is needed to confirm efficacy and to determine the balance of potential benefits and harms.
Published: 2022
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7. Absence of Mortality Differences Between the First and Second COVID-19 Waves in Kidney Transplant Recipients

Author: Bastien Berger, Marc Hazzan, Nassim Kamar, Hélène Francois, Marie Matignon, Clarisse Greze, Philippe Gatault, Luc Frimat, Pierre F. Westeel, Valentin Goutaudier, Renaud Snanoudj, Charlotte Colosio, Antoine Sicard, Dominique Bertrand, Christiane Mousson, Jamal Bamoulid, Antoine Thierry, Dany Anglicheau, Lionel Couzi, Jonathan M. Chemouny, Agnes Duveau, Valerie Moal, Yannick Le Meur, Gilles Blancho, Jérôme Tourret, Paolo Malvezzi, Christophe Mariat, Jean-Philippe Rerolle, Nicolas Bouvier, Sophie Caillard, Olivier Thaunat, Hospices Civils de Lyon (HCL), 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), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Inserm UMR 1227 Immunothérapies et Pathologies Lymphocytaires B, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), OT is supported by the Etablissement Français du Sang and the Fondation pour la Recherche Médicale (PME20180639518)., 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 ), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and 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)
Subjects: Transplantation, Nephrology, [SDV]Life Sciences [q-bio], SARS-CoV2
Abstract: International audience; Introduction - SARS-CoV-2 pandemic evolved in 2 consecutive waves during 2020. Improvements in the management of COVID-19 led to a reduction in mortality rates among hospitalized patients during the second wave. Whether this progress benefited kidney transplant recipients (KTRs), a population particularly vulnerable to severe COVID-19, remained unclear. Methods - In France, 957 KTRs were hospitalized for COVID-19 in 2020 and their data were prospectively collected into the French Solid Organ Transplant (SOT) COVID registry. The presentation, management, and outcomes of the 359 KTRs diagnosed during the first wave were compared to those of the 598 of the second wave. Results - Baseline comorbidities were similar between KTRs of the 2 waves. Maintenance immunosuppression was reduced in most patients but withdrawal of antimetabolite (73.7% vs. 58.4%, < 0.001) or calcineurin inhibitor (32.1% vs. 16.6%, < 0.001) was less frequent during the second wave. Hydroxychloroquine and azithromycin that were commonly used during the first wave (21.7% and 30.9%, respectively) but were almost abandoned during the second wave. In contrast, the use of high dose corticosteroids doubled (19.5% vs. 41.6%, < 0.001). Despite these changing trends in COVID-19 management, 60-day mortality was not statistically different between the 2 waves (25.3% vs. 23.9%; Log Rank, = 0.48) and COVID-19 hospitalization period was not associated with death due to COVID-19 in multivariate analysis (Hazard ratio 0.89, 95% confidence interval 0.67-1.17, = 0.4). Conclusion - We conclude that changing of therapeutic trends during 2020 did not reduce COVID-19 related mortality among KTRs. Our data indirectly support the importance of vaccination and neutralizing monoclonal anti-SARS-CoV-2 antibodies to protect KTRS from severe COVID-19.
Published: 2022
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8. Comparison of scoring systems evaluating suitability for intensive chemotherapy in adults with acute myeloid leukemia-a Grand Ouest Against Leukemia (GOAL) study

Author: Christophe Desprez, Jérémie Riou, Pierre Peterlin, Tony Marchand, Marie-Anne Couturier, Alban Villate, Jean-Baptiste Mear, Patrice Chevalier, Gaelle Guillerm, Emmanuel Gyan, Aline Schmidt-Tanguy, Roland B. Walter, Mathilde Hunault-Berger, Corentin Orvain, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA), CHU Pontchaillou [Rennes], 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), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-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), and Fred Hutchinson Cancer Research Center [Seattle] (FHCRC)
Subjects: Adult, Cancer Research, Leukemia, Myeloid, Acute, Oncology, [SDV]Life Sciences [q-bio], Antineoplastic Combined Chemotherapy Protocols, Humans, Hematology, Induction Chemotherapy, Goals, Proportional Hazards Models
Abstract: International audience; Several scoring systems have been developed to assess suitability of individual patients for intensive acute myeloid leukemia (AML) therapy. We sought to compare the performance of these scores in a cohort of 428 consecutive adults with AML who received conventional induction chemotherapy in five academic centers in France. All scoring systems identified a subset of patients with increased 28 and 56-day mortality although the prediction accuracy was overall limited with C-statistics of ranging from 0.61 to 0.71 Overall survival (OS) prediction was more limited and restricted to scoring systems that include AML-related parameters. The outcome of 104 patients (24%) considered unsuitable for intensive chemotherapy based on criteria used in recent randomized trials was similar to that of the other 324 patients (28-day mortality, odds ratio [OR] = 1.88, P = 0.2; 56-day mortality, OR = 1.71, P = 0.21; event-free survival, hazard ratio [HR] = 1.08, P = 0.6; OS, HR = 1.25, P = 0.14) with low discrimination (C-statistic: 0.57, 0.56, 0.50, and 0.52 for 28-day, 56-day mortality, EFS, and OS, respectively). Together, our findings indicate that the accuracy of currently available approaches to identify patients at increased risk of early mortality and shortened survival after intensive AML therapy is relatively limited. Caution regarding the use of available scoring systems should be warranted in clinical decision-making.
Published: 2022
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9. Are Gadolinium-Enhanced MR Sequences Needed in Simultaneous 18F-FDG-PET/MRI for Tumor Delineation in Head and Neck Cancer?

Author: E. Chambenois, Didier Dormont, Aurélie Kas, S. Bergeret, Nadya Pyatigorskaya, R. De Laroche, G. Herve, C. Bertolus, M. Amor-Sahli, Alain Giron, G. Bera, Colliot, Olivier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Morvan - CHRU de Brest (CHU - BREST ), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = 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 National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Laboratoire d'Imagerie Biomédicale [Paris] (LIB)
Subjects: [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Gadolinium, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, chemistry.chemical_element, MESH: Magnetic Resonance Imaging, 030218 nuclear medicine & medical imaging, 18f fdg pet, 03 medical and health sciences, [INFO.INFO-CV] Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], 0302 clinical medicine, Text mining, MESH: Fluorodeoxyglucose F18, MESH: Contrast Media, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Radiology, Nuclear Medicine and imaging, Head and neck, [SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing, MESH: Aged, MESH: Humans, MESH: Middle Aged, business.industry, Head and neck cancer, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], MESH: Adult, MESH: Retrospective Studies, medicine.disease, Mr imaging, MESH: Male, MESH: Positron-Emission Tomography, MESH: Sensitivity and Specificity, 3. Good health, MESH: Head and Neck Neoplasms, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, [INFO.INFO-TI] Computer Science [cs]/Image Processing [eess.IV], chemistry, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Neurology (clinical), MESH: Gadolinium, business, Nuclear medicine, MESH: Female, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, MESH: Radiopharmaceuticals, 030217 neurology & neurosurgery
Abstract: International audience; PET/MRI with 18F-FDG has demonstrated the advantages of simultaneous PET and MR imaging in head and neck cancer imaging, MRI allowing excellent soft-tissue contrast, while PET provides metabolic information. The aim of this study was to evaluate the added value of gadolinium contrast-enhanced sequences in the tumor delineation of head and neck cancers on 18F-FDG-PET/MR imaging.
Published: 2020
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10. Brigatinib for Pretreated, ALK-Positive, Advanced Non-Small-Cell Lung Cancers: Long-Term Follow-Up and Focus on Post-Brigatinib Lorlatinib Efficacy in the Multicenter, Real-World BrigALK2 Study

Author: Renaud Descourt, Maurice Pérol, Gaëlle Rousseau-Bussac, David Planchard, Bertrand Mennecier, Marie Wislez, Jacques Cadranel, Alexis Benjamin Cortot, Florian Guisier, Loïck Galland, Pascal Do, Roland Schott, Éric Dansin, Jennifer Arrondeau, Jean-Bernard Auliac, Margaux Geier, Christos Chouaïd, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Centre Régional de Lutte Contre le Cancer Lyon Rhône-Alpes (CLB), Centre Hospitalier Intercommunal de Créteil (CHIC), Institut Gustave Roussy (IGR), CHU Strasbourg, Cancer Research and Personalized Medicine - CARPEM [Paris], 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)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [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 (UPCité), Groupe de recherche clinique Biomarqueurs Théranostiques des Cancers Bronchiques Non à Petites Cellules (GRC 4 - Theranoscan), Sorbonne Université (SU), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Georges-François-Leclerc, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Institut de Cancérologie de Strasbourg Europe (ICANS), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Hôpital Cochin [AP-HP], Service de Pneumologie [CHI Créteil], CHI Créteil, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), and 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)
Subjects: Cancer Research, brigatinib, Oncology, lorlatinib, ALK rearrangment, NSCLC, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: Brigatinib is a next-generation ALK inhibitor (ALKi) that shows efficacy in ALK inhibitor naïve and post-crizotinib ALK+ advanced NSCLCs (aNSCLCs). The efficacy of brigatinib was retrospectively assessed in patients with aNSCLCs included in the brigatinib French Early-Access Program (1 August 2016–21 January 2019). The primary endpoint was investigator-assessed progression-free survival (invPFS) and the primary analysis was updated in 2021 with a longer follow-up, focused on post-brigatinib lorlatinib efficacy. Sixty-six centers included 183 patients: median age 60 ± 12.7 years; 78.3% never/former smokers; median of 3 ± 1 previous lines and 2 ± 0.5 ALKis; 37.1% ECOG PS 2 and 55.6% >3 metastatic sites. The median follow-up from brigatinib initiation was 40.4 months (95% CI 38.4–42.4). InvPFS was 7.4 months (95% CI 5.9–9.6), median duration of treatment (mDOT) was 7.3 months (95% CI 5.8–9.4) and median overall survival (mOS) was 20.3 months (95% CI 15.6–27.6). The median DOT and OS from brigatinib initiation tend to decrease with the number of ALK inhibitors used in previous lines of therapy. Based on the data collected, 92 (50.3%) patients received ≥1 agent(s) post-brigatinib and 68 (73.9%) of them received lorlatinib, with 51 (75%) immediately receiving it post-brigatinib, 12 (17.6%) receiving it after one and 5 (7.4%) after ≥2 subsequent treatments. The median follow-up was 29.9 (95% CI 25.7–33.1) months. Lorlatinib mDOT was 5.3 (95% CI 3.6–7.6) months with a median OS from lorlatinib initiation of 14.1 (95% CI 10.3–19.2) months. The results of the brigALK2 study confirm the efficacy of brigatinib in a population of heavily pretreated ALK+ aNSCLC patients and provide new data on the activity of lorlatinib after brigatinib.
Published: 2022
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11. Chilblains during lockdown are associated with household exposure to SARS-CoV-2. A multicentre case-control study

Author: Alexis Toubel, Catherine Droitcourt, Ludovic Martin, Florence Poizeau, Laurent Misery, Yannick Le Corre, Pierre Tattevin, Valérie Gissot, Emmanuel Oger, C. Laurent, Alain Dupuy, Vincent Thibault, Mahtab Samimi, Hélène Aubert, Emilie Brenaut, Estel Chambrelan, Sébastien Barbarot, Christopher Heslan, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Physiopathologie des Adaptations Nutritionnelles (PhAN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Morvan - CHRU de Brest (CHU - BREST ), CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), 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 ), This work was supported by a grant from the Programme Hospitalier de Recherche Clinique Interrégional (Ministry of Health) GRICI Grand-Ouest., Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Jonchère, Laurent
Subjects: Microbiology (medical), Referral, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], chilblains, Serology, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Environmental health, Pandemic, Healthy volunteers, medicine, Humans, 030212 general & internal medicine, Chilblains, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Pandemics, Pernio, business.industry, SARS-CoV-2, Case-control study, COVID-19, General Medicine, Acralmanifestations, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Case-Control Studies, Communicable Disease Control, Original Article, Perniosis, business
Abstract: International audience; OBJECTIVES: During the COVID-19 pandemic, numerous cases of chilblains have been reported. However, in most cases, RT-PCR or serology did not confirm SARS-CoV-2 infection. Hypotheses have been raised about an interferon-mediated immunological response to SARS-CoV-2, leading to effective clearance of the SARS-CoV-2 without the involvement of humoral immunity. Our objective was to explore the association between chilblains and exposure to SARS-CoV-2. METHODS: In this multicentre case-control study, cases were the 102 individuals referred to 5 referral hospitals for chilblains occurring during the first lockdown (March to May 2020). Controls were recruited from healthy volunteers’ files held by the same hospitals. All members of their households were included, resulting in 77 case households (262 individuals) and 74 control households (230 individuals). Household exposure to SARS-CoV-2 during the first lockdown was categorized as high, intermediate or low, using a pre-established algorithm based on individual data on symptoms, high-risk contacts, activities outside the home and RT-PCR testing. Participants were offered a SARS-CoV-2 serological test. RESULTS: After adjustment for age, the association between chilblains and viral exposure was estimated at OR=3.3, 95%CI (1.4-7.3) for an intermediate household exposure, and 6.9 (2.5-19.5) for a high household exposure to SARS-CoV-2. Out of 57 case households tested, 6 (11%) had positive serology for SARS-CoV-2, whereas all control households tested (n=50) were seronegative (p=0.03). The effect of potential misclassification on exposure has been assessed in a bias analysis. CONCLUSIONS: This case-control study demonstrates the association between chilblains occurring during the lockdown and household exposure to SARS-CoV-2. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04455308.
Published: 2022
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12. Pooled Fecal Allogenic Microbiotherapy for Refractory Gastrointestinal Acute Graft-Versus-Host Disease: Results from the Early Access Program in France

Author: Florent Malard, Michael Loschi, Thomas Cluzeau, Faezeh Legrand, Jean-Baptiste Mear, Faustine Lhomme, Sarah Guenounou, Anne Huynh, Cecile Borel, Deborah Desmier, Niels Moya, Amandine Charbonnier, Delphine Lebon, Hélène Labussière-Wallet, Corentin Orvain, Sylvain Chantepie, Claude-Eric Bulabois, Vincent Camus, Marie-Anne Couturier, Jérôme Cornillon, Patrice Chevallier, Clémence Mediavilla, Patrice Ceballos, David Beauvais, Marion Bruelle, Emilie Plantamura, Mohamad Mohty, DESSAIVRE, Louise, Service d'hématologie clinique et de thérapie cellulaire [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), 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), Centre Hospitalier Universitaire de Nice (CHU Nice), Université Côte d'Azur (UCA), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU Pontchaillou [Rennes], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Laboratoire d'Hématologie [CHU Amiens], CHU Amiens-Picardie, Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Grenoble, Université Grenoble Alpes (UGA), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Institut de Cancérologie Lucien Neuwirth, CHU Saint-Etienne, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Lille, MaaT Pharma [Lyon], CEREST-TC [CHU Saint-Antoine], and Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP]
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Immunology, Cell Biology, Hematology, Biochemistry, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Introduction Acute graft-versus-host disease (aGvHD) is a major source of mortality following allogeneic hematopoietic cell transplantation (allo-HCT). Standard 1st line therapy for the treatment of aGvHD involves corticosteroids (CS). However, more than 50% of patients are refractory to CS (SR-aGvHD) and the associated mortality rate is of up to 80%. Recently, Ruxolitinib has been approved as 2nd line treatment for SR-aGvHD. However, patients with severe gastrointestinal (GI) aGvHD seem less likely to respond to Ruxolitinib and have poor outcomes with limited therapeutic options.In this context, fecal microbiotherapy has shown promising results in several pilot studies in patients with refractory GI-aGvHD. Here we report clinical outcomes from 81 patients diagnosed with SR or dependent (SD) GI-aGvHD treated with the pooled allogeneic microbiotherapy MaaT013 as part of the Early Access Program (EAP) in France.Methods 81 patients with SR/SD GI-aGvHD (Classical n=62, late onset n=12, overlap syndrome n=7) were treated with MaaT013 as part of an EAP in France. These patients had failed 1 to 6 prior systemic GvHD treatment lines (median 2; 66/81 received Ruxolitinib). Most patients had grade III-IV aGvHD (11% grade II, 51% grade III, 38% grade IV).For each patient, a total of 3 MaaT013 administrations were planned every 7 +/- 2 days. Each dose comprised 30g of feces in 150 mL of diluent, from 4 to 8 healthy donors, administered by enema (except for 1 patient by nasogastric tube).Treatment response was calculated among all treated patients based on aGvHD staging and grading at day 28 (D28) at the time of the EAP request.Results At D28, the GI-overall response rate (ORR) was 56%: 30 complete response (CR, 37%), 11 very good response rate (VGPR, 14%), 4 partial response (PR, 5%). The GI-ORR was higher in patients with lower grade aGvHD (89% in grade II, 66% in grade III, 32% in grade IV) and higher in SD versus SR patients (92% versus 49%). Including skin and liver symptoms (n=78), response rate was 49%, including 24 CR, 11 VGPR and 3 PR and inversely correlated with aGvHD initial grade (88% in grade II, 55% in grade III, 30% in grade IV).Overall survival (OS) was 51% at 6 months (M6) and 39% at M12. The median follow-up among surviving patients was 355 days (range, 53-731). OS was significantly higher in patients achieving at least GI-PR at D28 (Responder, R; n=45) compared to patients in treatment failure (Non-responder, NR; n=35): 69% versus 28% at M6, 59% versus 14% at M12, respectively. Median survival duration in R was 451 days versus 32 days in NR.Interestingly, aGvHD response was improved in the subgroup of 31 patients previously treated with Ruxolitinib as 2nd line and MaaT013 as 3rd line (65% D28 GI-ORR, OS M6 55% and 49% M12 and 74% versus 15% at M6 and 74% versus 0% at M12 for R and NR respectively).MaaT013 displayed a good overall safety profile in the EAP population: 20 pharmacovigilance cases were reported in 18 patients: sepsis in 11 patients, C. difficile colitis in 2, E. coli osteoarthritis in 1, G. silvicola in stools from 1, P. aeruginosa sinusitis in 1, appearance of air bubbles in the mesorectum in 1, respiratory distress in 1. No pathogen transmission was reported. In 2 patients, non-pathogenic commensal bacteria isolated following infectious events were detected in the administered MaaT013 batch. Causality could not be formally excluded in these cases.The overall incidence of bacteremia (14%) remains low, compared to an incidence of 31% to 74% in bloodstream infections reported in patients with GI-aGvHD. This suggests that fecal microbiotherapy may have a protective effect on bacterial translocation, but this needs to be confirmed in further clinical trials.47 deaths have been reported; the cause of which was GvHD in 21 patients, severe infection in 13, relapse of underlying malignancy in 6, COVID-19 in 3, hemorrhage during surgery in 1, neurological complications post allo-HCT in 1, and cardiac arrest in 2 patients. No causality link with MaaT013 administration has been identified.Conclusion Overall, EAP clinical data showed that MaaT013 was safe and effective for the treatment of SR/SD-GI-aGvHD especially in patients having previously received ruxolitinib. Interestingly, GI-response to aGvHD correlates with increased OS, suggesting a strong favorable benefit-risk profile for MaaT013. A Phase 3 trial is currently ongoing to confirm these results in ruxolitinib-refractory patients (NCT04769895).
Published: 2022
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13. SEMA6B variants cause intellectual disability and alter dendritic spine density and axon guidance

Author: Amélie Cordovado, Martina Schaettin, Médéric Jeanne, Veranika Panasenkava, Anne-Sophie Denommé-Pichon, Boris Keren, Cyril Mignot, Martine Doco-Fenzy, Lance Rodan, Keri Ramsey, Vinodh Narayanan, Julie R Jones, Eloise J Prijoles, Wendy G Mitchell, Jillian R Ozmore, Kali Juliette, Erin Torti, Elizabeth A Normand, Leslie Granger, Andrea K Petersen, Margaret G Au, Juliann P Matheny, Chanika Phornphutkul, Mary-Kathryn Chambers, Joaquín-Alejandro Fernández-Ramos, Eduardo López-Laso, Michael C Kruer, Somayeh Bakhtiari, Marcella Zollino, Manuela Morleo, Giuseppe Marangi, Davide Mei, Tiziana Pisano, Renzo Guerrini, Raymond J Louie, Anna Childers, David B Everman, Betrand Isidor, Séverine Audebert-Bellanger, Sylvie Odent, Dominique Bonneau, Brigitte Gilbert-Dussardier, Richard Redon, Stéphane Bézieau, Frédéric Laumonnier, Esther T Stoeckli, Annick Toutain, Marie-Laure Vuillaume, Jonchère, Laurent, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universität Zürich [Zürich] = University of Zurich (UZH), FHU TRANSLAD (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hémostase et Remodelage Vasculaire Post-Ischémie (HERVI - EA 3801), Université de Reims Champagne-Ardenne (URCA), Boston Children's Hospital, Harvard Medical School [Boston] (HMS), The Translational Genomics Research Institute (TGen), The Greenwood Genetic Center, Keck School of Medicine [Los Angeles], University of Southern California (USC), Dartmouth Hitchcock Medical Center [Lebanon], Gillette Children's Specialty Healthcare [St Paul], GeneDx [Gaithersburg, MD, USA], Randall Children's Hospital [Portland], University of Kentucky (UK), Warren Alpert Medical School of Brown University, Rhode Island Hospital [Providence, RI, États-Unis], Instituto Maimonides de Investigación Biomédica de Cordoba (IMIBIC), Universidad de Córdoba = University of Córdoba [Córdoba]-Hospital Universitario Reina Sofía, Barrow Neurological Institute, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Telethon Institute of Genetics and Medicine = Istituto Telethon di Genetica e Medicina (TIGEM), Università degli Studi di Firenze = University of Florence (UniFI), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], 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), 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), Funding for HUGODIMS (Western France exome-based trio approach project to identifygenes involved in intellectual disability) was supported by a grant from the French Ministryof Health and from the Health Regional Agency from Poitou-Charentes [HUGODIMS, 2013,RC14_0107]. [A.C.] is a research student recipient of a grant from the University of Tours., Cordovado, Amélie, Schaettin, Martina, Jeanne, Médéric, Panasenkava, Veranika, Denommé-Pichon, Anne-Sophie, Keren, Bori, Mignot, Cyril, Doco-Fenzy, Martine, Rodan, Lance, Ramsey, Keri, Narayanan, Vinodh, Jones, Julie R, Prijoles, Eloise J, Mitchell, Wendy G, Ozmore, Jillian R, Juliette, Kali, Torti, Erin, Normand, Elizabeth A, Granger, Leslie, Petersen, Andrea K, Au, Margaret G, Matheny, Juliann P, Phornphutkul, Chanika, Chambers, Mary-Kathryn, Fernández-Ramos, Joaquín-Alejandro, López-Laso, Eduardo, Kruer, Michael C, Bakhtiari, Somayeh, Zollino, Marcella, Morleo, Manuela, Marangi, Giuseppe, Mei, Davide, Pisano, Tiziana, Guerrini, Renzo, Louie, Raymond J, Childers, Anna, Everman, David B, Isidor, Betrand, Audebert-Bellanger, Séverine, Odent, Sylvie, Bonneau, Dominique, Gilbert-Dussardier, Brigitte, Redon, Richard, Bézieau, Stéphane, Laumonnier, Frédéric, Stoeckli, Esther T, Toutain, Annick, and Vuillaume, Marie-Laure
Subjects: [SDV.GEN]Life Sciences [q-bio]/Genetics, Epilepsy, Dendritic Spines, [SDV]Life Sciences [q-bio], Intellectual disability, Chick Embryo, Semaphorins, [SDV.GEN] Life Sciences [q-bio]/Genetics, General Medicine, Settore MED/03 - GENETICA MEDICA, Axon Guidance, [SDV] Life Sciences [q-bio], HEK293 Cells, SEMA6B, Intellectual Disability, Genetics, Animals, Humans, Original Article, Molecular Biology, Genetics (clinical)
Abstract: Intellectual disability (ID) is a neurodevelopmental disorder frequently caused by monogenic defects. In this study, we collected 14 SEMA6B heterozygous variants in 16 unrelated patients referred for ID to different centers. Whereas, until now, SEMA6B variants have mainly been reported in patients with progressive myoclonic epilepsy, our study indicates that the clinical spectrum is wider and also includes non-syndromic ID without epilepsy or myoclonus. To assess the pathogenicity of these variants, selected mutated forms of Sema6b were overexpressed in Human Embryonic Kidney 293T (HEK293T) cells and in primary neuronal cultures. shRNAs targeting Sema6b were also used in neuronal cultures to measure the impact of the decreased Sema6b expression on morphogenesis and synaptogenesis. The overexpression of some variants leads to a subcellular mislocalization of SEMA6B protein in HEK293T cells and to a reduced spine density owing to loss of mature spines in neuronal cultures. Sema6b knockdown also impairs spine density and spine maturation. In addition, we conducted in vivo rescue experiments in chicken embryos with the selected mutated forms of Sema6b expressed in commissural neurons after knockdown of endogenous SEMA6B. We observed that expression of these variants in commissural neurons fails to rescue the normal axon pathway. In conclusion, identification of SEMA6B variants in patients presenting with an overlapping phenotype with ID and functional studies highlight the important role of SEMA6B in neuronal development, notably in spine formation and maturation and in axon guidance. This study adds SEMA6B to the list of ID-related genes.
Published: 2022
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14. Should prenatal chromosomal microarray analysis be offered for isolated fetal growth restriction? A French multicenter study

Author: Jérôme Massardier, Valérie Goua, Aline Receveur, Pascale Kleinfinger, Isabelle Monier, Véronique Houfflin-Debarge, Florent Fuchs, Anne-Hélène Saliou, Guillaume Benoist, Marion Groussolles, Anne-Sylvie Valat, Alexandra Benachi, Sophie Degre, Jennifer Zeitlin, Vanina Castaigne, Jean-Marie Jouannic, Hanane Bouchghoul, Vassilis Tsatsaris, Eve Mousty, Thierry Rousseau, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Saclay, Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Intercommunal de Créteil (CHIC), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Hôpital Bicêtre, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CH Lens, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CH Le Havre, Hospices Civils de Lyon (HCL), Hôpital Cochin [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Laboratoire CERBA [Saint Ouen l'Aumône], and Fuchs, Florent
Subjects: Adult, Prenatal diagnosis, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Andrology, fetal growth restriction, 03 medical and health sciences, 0302 clinical medicine, chromosomal microarray, Pregnancy, medicine, Humans, 030212 general & internal medicine, Copy-number variation, Retrospective Studies, Fetus, Fetal Growth Retardation, 030219 obstetrics & reproductive medicine, prenatal diagnosis, Microarray analysis techniques, business.industry, Obstetrics and Gynecology, Karyotype, General Medicine, Microarray Analysis, medicine.disease, Confidence interval, karyotype, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, embryonic structures, Female, France, Trisomy, business, copy number variants
Abstract: International audience; Background: Compared with standard karyotype, chromosomal microarray analysis improves the detection of genetic anomalies and is thus recommended in many prenatal indications. However, evidence is still lacking on the clinical utility of chromosomal microarray analysis in cases of isolated fetal growth restriction.Objective: This study aimed to estimate the proportion of copy number variants detected by chromosomal microarray analysis and the incremental yield of chromosomal microarray analysis compared with karyotype in the detection of genetic abnormalities in fetuses with isolated fetal growth restriction.Study design: This retrospective study included all singleton fetuses diagnosed with fetal growth restriction and no structural ultrasound anomalies and referred to 13 French fetal medicine centers over 1 year in 2016. Fetal growth restriction was defined as an estimated fetal weight of
Published: 2021
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15. A new molecular classification to drive precision treatment strategies in primary Sjögren’s syndrome

Author: Soret, Perrine, Le Dantec, Christelle, Desvaux, Emiko, Foulquier, Nathan, Chassagnol, Bastien, Hubert, Sandra, Christophe, Jamin, Barturen, Guillermo, Desachy, Guillaume, Devauchelle-Pensec, Valérie, Boudjeniba, Cheïma, Cornec, Divi, Saraux, Alain, Jousse-Joulin, Sandrine, Barbarroja, Nuria, Rodríguez-Pintó, Ignasi, de Langhe, Ellen, Beretta, Lorenzo, Chizzolini, Carlo, Kovács, László, Witte, Torsten, Bettacchioli, Eléonore, Buttgereit, Anne, Makowska, Zuzanna, Lesche, Ralf, Borghi, Maria Orietta, Martin, Javier, Courtade-Gaiani, Sophie, Xuereb, Laura, Guedj, Mickaël, Moingeon, Philippe, Alarcón-Riquelme, Marta, Laigle, Laurence, Pers, Jacques-Olivier, Vigone, Barbara, Lauwerys, Bernard, Maudoux, Anne-Lise, Vasconcelos, Carlos, Tavares, Ana, Faria, Raquel, Brandão, Mariana, Campar, Ana, Marinho, António, Farinha, Fátima, Almeida, Isabel, Gonzalez-Gay Mantecón, Miguel Angel, Blanco Alonso, Ricardo, Corrales Martínez, Alfonso, Cervera, Ricard, Espinosa, Gerard, Lories, Rik, Hunzelmann, Nicolas, Belz, Doreen, Baerlecken, Niklas, Stummvoll, Georg, Zauner, Michael, Lehner, Michaela, Collantes, Eduardo, Ortega-Castro, Rafaela, Aguirre-Zamorano, Ma Angeles, Escudero-Contreras, Alejandro, Castro-Villegas, Ma Carmen, Jiménez Gómez, Yolanda, Ortego, Norberto, Fernández Roldán, María Concepción, Raya, Enrique, Jiménez Moleón, Inmaculada, de Ramon, Enrique, Díaz Quintero, Isabel, Meroni, Pier Luigi, Gerosa, Maria, Schioppo, Tommaso, Artusi, Carolina, Zuber, Aleksandra, Wynar, Donatienne, Balog, Attila, Deák, Magdolna, Bocskai, Márta, Dulic, Sonja, Kádár, Gabriella, Hiepe, Falk, Thiel, Silvia, Rodriguez Maresca, Manuel, López-Berrio, Antonio, Aguilar-Quesada, Rocío, Navarro-Linares, Héctor, Ioannou, Yiannis, Chamberlain, Chris, Marovac, Jacqueline, Alarcón Riquelme, Marta, Gomes Anjos, Tania, Marañón, Concepción, Le Lann, Lucas, Simon, Quentin, Rouvière, Bénédicte, Varela, Nieves, Muchmore, Brian, Dufour, Aleksandra, Alvarez, Montserrat, Cremer, Jonathan, Lopez-Pedrera, Chary, Gerl, Velia, Khodadadi, Laleh, Cheng, Qingyu, de Groof, Aurélie, Ducreux, Julie, Trombetta, Elena, Li, Tianlu, Alvarez-Errico, Damiana, Kniesch, Katja, Azevedo, Nancy, Neves, Esmeralda, Rao, Sambasiva, Jouve, Pierre-Emmanuel, Institut de Recherches Internationales Servier [Suresnes] (IRIS), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre for Genomics and Oncological Reearch (GENYO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Instituto Maimonides de Investigación Biomédica de Cordoba (IMIBIC), Universidad de Córdoba = University of Córdoba [Córdoba]-Hospital Universitario Reina Sofía, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Maggiore Hospital, IRCCS Foundation, Milano, Department of Pathology and Immunology [Geneva, Switzerland], Université de Genève = University of Geneva (UNIGE), University of Szeged [Szeged], Clinic for Immunology and Rhematology, Hannover Medical School, Hanover, Germany, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Pharmaceuticals Division Bayer Pharma Aktiengesellschaft, Università degli Studi di Milano = University of Milan (UNIMI), Instituto de Parasitología y Biomedicina 'López-Neyra' (IPBLN), Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Granada = University of Granada (UGR), and Michel, Geneviève
Subjects: MESH: Databases, Protein, MESH: Inflammation, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Flow Cytometry, MESH: Cross-Sectional Studies, MESH: DNA Methylation, MESH: Computer Simulation, cell cycle, chronic lymphocytic leukemia, liquid chromatography-tandem mass spectrometry, splicing, MESH: Autoantibodies, MESH: Interferons, MESH: RNA-Seq, MESH: Cohort Studies, MESH: Databases, Genetic, MESH: Cytokines, MESH: Humans, MESH: Middle Aged, MESH: Polymorphism, Single Nucleotide, MESH: Transcriptome, MESH: Adult, MESH: Chemokines, MESH: Male, MESH: Proteome, MESH: Sjogren's Syndrome, MESH: Genome-Wide Association Study, MESH: Biomarkers, MESH: Multigene Family, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Female, MESH: Computational Biology
Abstract: International audience; Abstract There is currently no approved treatment for primary Sjögren’s syndrome, a disease that primarily affects adult women. The difficulty in developing effective therapies is -in part- because of the heterogeneity in the clinical manifestation and pathophysiology of the disease. Finding common molecular signatures among patient subgroups could improve our understanding of disease etiology, and facilitate the development of targeted therapeutics. Here, we report, in a cross-sectional cohort, a molecular classification scheme for Sjögren’s syndrome patients based on the multi-omic profiling of whole blood samples from a European cohort of over 300 patients, and a similar number of age and gender-matched healthy volunteers. Using transcriptomic, genomic, epigenetic, cytokine expression and flow cytometry data, combined with clinical parameters, we identify four groups of patients with distinct patterns of immune dysregulation. The biomarkers we identify can be used by machine learning classifiers to sort future patients into subgroups, allowing the re-evaluation of response to treatments in clinical trials.
Published: 2021
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16. Serological biomarkers for the diagnosis of Mycobacterium abscessus infections in cystic fibrosis patients

Author: Jean-Louis Herrmann, Jean-Louis Gaillard, Anne-Laure Roux, Gaëtan Christien, Jean-Philippe Bouchara, Hélène Mahoudo, Agnès Ferroni, Gerard Lina, Oana Dumitrescu, Vincent Le Moigne, Patrick Plésiat, Stéphane Canaan, Geneviève Héry-Arnaud, Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Laboratoire de Parasitologie-Mycologie (CHU d'Angers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'ingénierie des systèmes macromoléculaires (LISM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Saclay, Hôpital Ambroise Paré [AP-HP], Laboratoire de Microbiologie Clinique [AP-HP Hôpital Necker-Enfants Malades], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Infections Respiratoires Fongiques (IRF), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université de Bourgogne (UB), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de microbiologie, APHP Raymond Poincaré, This work was supported by grants from the Association Vaincre la Mucoviscidose (RF20110600446/1/3/130)., Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université d'Angers (UA)-Université de Brest (UBO)
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Mycobacterium Infections, Nontuberculous, Mycobacterium abscessus, Cystic fibrosis, Gastroenterology, Serology, 03 medical and health sciences, 0302 clinical medicine, Antigen, Internal medicine, Non-tuberculous mycobacteria, medicine, Humans, 030212 general & internal medicine, Pathogen, ComputingMilieux_MISCELLANEOUS, Serodiagnosis, biology, business.industry, Antibody titer, Nontuberculous Mycobacteria, medicine.disease, biology.organism_classification, bacterial infections and mycoses, 3. Good health, Mycobacterium abscessus Infections, 030228 respiratory system, Serological biomarkers, Pediatrics, Perinatology and Child Health, ELISA, business, Biomarkers
Abstract: International audience; Background: Culture conditions sometimes make it difficult to detect non-tuberculous mycobacteria (NTM), particularly Mycobacterium abscessus, an emerging cystic fibrosis (CF) pathogen. The diagnosis of NTM positive cases not detected by classical culture methods might benefit from the development of a serological assay.Methods: As part of a diagnostic accuracy study, a total of 173 sera CF-patients, including 33 patients with M. abscessus positive cultures, and 31 non-CF healthy controls (HC) were evaluated. Four M. abscessus antigens were used separately, comprising two surface extracts (Interphase (INP) and a TLR2 positive extract (TLR2eF)) and two recombinant proteins (rMAB_2545c and rMAB_0555 also known as the phospholipase C (rPLC)).Results: TLR2eF and rPLC were the most efficient antigens to discriminate NTM-culture positive CF-patients from NTM-culture negative CF-patients. The best clinical values were obtained for the detection of M. abscessus-culture positive CF-patients; with sensitivities for the TLR2eF and rPLC of 81.2% (95% CI:65.7-92.3%) and 87.9% (95% CI:71.9-95.6%) respectively, and specificities of 88.9% (95% CI:85.3-94.8%) and 84.8% (95% CI:80.6-91.5%) respectively. When considering as positive all sera, giving a positive response in at least one of the two tests, and, as negative, all sera negative for both tests, we obtained a sensitivity of 93.9% and a specificity of 80.7% for the detection of M. abscessus-culture positive CF-patients.Conclusion: High antibody titers against TLR2eF and rPLC were obtained in M. abscessus-culture positive CF-patients, allowing us to consider these serological markers as potential tools in the detection of CF-patients infected with M. abscessus.
Published: 2021
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17. Autosomal dominant SPG9: intrafamilial variability and onset during pregnancy

Author: Claire Guissart, M. Planes, Michel Koenig, P. Damier, Steeve Genestet, W. Camu, Lise Larrieu, Cecilia Marelli, Stéphanie Badiou, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de neurologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Centre référent Sclérose Latérale Amyotrophique [CHRU Montpellier] (SLA CHRU Montpellier), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Morvan - CHRU de Brest (CHU - BREST ), and MORNET, Dominique
Subjects: medicine.medical_specialty, Neurology, Metabolic diseases (inherited), [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Dermatology, Disease, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Variable Expression, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pregnancy, Internal medicine, Genetics, medicine, Citrulline, Spastic, Humans, 030212 general & internal medicine, Child, Arthrogryposis, Paraplegia, Spastic Paraplegia, Hereditary, business.industry, Spastic paraplegia, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, General Medicine, Aldehyde Dehydrogenase, medicine.disease, Pedigree, 3. Good health, Psychiatry and Mental health, Endocrinology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, chemistry, Biomarker (medicine), Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: International audience; INTRODUCTION: The ALDH18A1 gene, encoding delta-1-pyrroline-5-carboxylate synthase (P5CS), is responsible for an autosomal recessive disease with severe developmental delay; more recently, ALDH18A1 was found to be responsible for SPG9, an autosomal dominant (AD) spastic paraplegia.CASE REPORT: We report a three-generation family with AD SPG9, initially suspected because of low citrulline on fasting plasma amino acid chromatography (AAC). Interestingly, in two patients, the spastic paraplegia appeared during pregnancy. One subject presented a severe childhood-onset form while another subject had a mild late-onset disease.CONCLUSION: The description of this family is of particular interest: it highlights the possibility of transient or permanent aggravation of spastic paraplegia due to SPG9 during pregnancy, suggesting a direct link between neurological symptoms and amino acid defect in a period of higher requirements and the potential benefit of amino acid supplementation; it underscores the value of plasma citrulline on fasting plasma AAC as a biomarker for this disease; it shows the variable expression of the disease.
Published: 2020
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18. Tabac et travail

Author: V. Le Denmat, Jean-Dominique Dewitte, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Laboratoire d'Études et de Recherche en Sociologie (LABERS), Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Brestois des Sciences de l'Homme et de la Société (IBSHS), and Université de Brest (UBO)
Subjects: Pulmonary and Respiratory Medicine, 03 medical and health sciences, 0302 clinical medicine, [SDV]Life Sciences [q-bio], 030212 general & internal medicine, 030210 environmental & occupational health, 3. Good health
Abstract: Resume Introduction Les barometres sante realises en France depuis plus de 15 ans montrent des differences de prevalence du tabagisme en fonction du statut d’activite et des categories socioprofessionnelles. Les relations entre tabac et travail ne se limitent pas a cela. Etats des connaissances Le tabagisme des salaries est classiquement decrit comme entrainant un surcout pour les entreprises, mais le cout reel du tabagisme en entreprise est difficile a evaluer. La co-exposition au tabac et aux toxiques rencontres dans certains milieux professionnels comporte un risque accru de developper une pathologie, cancer broncho-pulmonaire et bronchopneumopathie chronique obstructive notamment. L’entreprise peut egalement etre un lieu d’exposition au tabagisme passif qui touche inegalement les salaries. En France, l’usage du tabac et celui de la cigarette electronique en entreprise sont reglementes respectivement depuis 2006 et 2016. Perspectives Les programmes de sevrage en entreprise et l’interdiction de fumer sur le lieu de travail semblent inciter au sevrage tabagique. L’aide au sevrage tabagique par les medecins du travail pourrait aller dans le meme sens. Les sujets exposes aux cancerogenes professionnels et au tabac pourraient beneficier d’un depistage par scanner faiblement dose apres une phase d’experimentation destinee a valider l’interet de ce dispositif. Conclusion Les lieux de travail peuvent etre des lieux de prevention et d’aide au sevrage tabagique.
Published: 2019
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19. First trimester serum biomarkers in pregnancies complicated with placental chronic inflammation

Author: Pascale Marcorelles, Brigitte Pan Petesch, Françoise Ledé, Marie-Pierre Moineau, C. Tremouilhac, Philippe Merviel, Karine Lacut, Emmanuelle Le Moigne, Annabelle Remoué, Maël Padelli, Claire de Moreuil, Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Laboratoire de Biochimie, Université de Brest (UBO), CHRU Brest - Laboratoire d'Anatomo-Pathologie (CHU - AnaPath), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Institut de cancérologie et d'hématologie [Brest], Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire sur les interactions Epithéliums Neurones (LIEN), CCSD, Accord Elsevier, and Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM)
Subjects: Adult, Placental growth factor, medicine.medical_specialty, Placenta Diseases, Placenta, [SDV]Life Sciences [q-bio], Intrauterine growth restriction, Inflammation, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Serum biomarkers, Humans, Medicine, 030212 general & internal medicine, Pregnancy outcomes, Retrospective Studies, 030219 obstetrics & reproductive medicine, business.industry, Obstetrics, Obstetrics and Gynecology, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Pregnancy Trimester, First, First trimester, Reproductive Medicine, Etiology, Small for gestational age, Female, medicine.symptom, business, Biomarkers
Abstract: This study aimed at determining if first trimester serum biomarkers could predict adverse pregnancy outcomes associated with villitis (VUE) and chronic intervillositis of unknown etiology (CIUE).Between January 2013 and June 2018, we selected from pathology department files placentas with VUE or CIUE associated with VUE and control placentas with available first trimester Down syndrome screening results. First trimester PAPP-A and βhCG levels were recorded. Placental growth factor (PlGF) levels were measured in patients with an available first trimester serum sample. Histological findings in placentas, course of pregnancies and newborns' characteristics were compared between cases and controls.78 cases and 75 controls were included. In cases, there were 21,8% intrauterine growth restriction (IUGR), 30,8% small for gestational age (SGA). Compared to controls, placentas from cases were smaller (425 g [IQR 370-480] vs 460 g [IQR 390-523], p = 0,03), showed more maternal vascular malperfusion features (79,5% vs 22,7%, p 0,0001) and more fetal vascular malperfusion features (33,3% vs 12%, p = 0,002). Cases had lower PlGF (29,74 pg/ml [IQR 19,74-36,17] vs 36,37 pg/ml [IQR 27,36-49,13], p = 0,007) and βhCG levels (0,74 MoM [IQR 0,53-1,12] vs 1,00 MoM [IQR 0,72-1,53], p = 0,002) than controls. These differences resulted from lower PlGF levels in VUE patients compared to CIUE associated with VUE patients and controls (28,35 vs 34,05 and 36,37 pg/ml, p = 0,01) and from lower βhCG levels in CIUE associated with VUE patients compared to VUE patients and controls (0,65 vs 0,86 and 1, p = 0,005).Low first trimester PlGF levels in cases, especially in VUE patients, suggest that reduced angiogenesis is involved in adverse pregnancy outcomes related to VUE.
Published: 2019
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20. Comprehensive Molecular Analysis of Serologically D-Negative and Weak/Partial D Phenotype in Thai Blood Donors

Author: Loann Raud, Pornlada Nuchnoi, Claude Férec, Charuporn Promwong, Yann Fichou, Jairak Thongbut, Mahidol University [Bangkok], Thai Red Cross Society, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Morvan - CHRU de Brest (CHU - BREST ), and PODEUR, Sophie
Subjects: medicine.medical_specialty, Genotype, [SDV]Life Sciences [q-bio], Population, RHD variants, 030204 cardiovascular system & hematology, Biology, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Molecular genetics, Multiplex polymerase chain reaction, medicine, Immunology and Allergy, Rh, Allele, education, Gene, Sanger sequencing, Genetics, education.field_of_study, Hematology, [SDV] Life Sciences [q-bio], Blood group, Phenotype, symbols, Rh blood group system, Research Article, 030215 immunology
Abstract: Background: Molecular genetics of the Rh system has been extensively studied in Caucasians, Black Africans, East Asians, and Indians more recently. In this work, we sought to investigate the molecular basis of variant D expression in the Thai population, which remains unknown. Materials and Methods: Blood samples from 450 Thai donors showing the variant D phenotype were collected. The RHD gene was analyzed by quantitative multiplex polymerase chain reaction of short fluorescent fragments and/or Sanger sequencing. Results: The most frequent alleles in 200 D-negative and 121 DEL samples were the whole RHD gene deletion and the Asian DEL alleles, respectively. In 129 weak/partial D samples, 36 variant alleles were identified, including eight novel alleles. RHD*06.03, which is common in variant D samples from South China, is the most prevalent variant allele, followed by the recently reported Indian RHD*01W.150 allele. Discussion: For the first time, a comprehensive overview of the nature and distribution of variant RHD alleles in Thailand is reported. It is a milestone to pave the way towards improvement of the current screening strategy to identify DEL donors accurately. The next step will be the design and implementation of a simple molecular test for screening the most frequent alleles, specifically in this population.
Published: 2019
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21. Missense Variants in the Histone Acetyltransferase Complex Component Gene TRRAP Cause Autism and Syndromic Intellectual Disability

Author: Philippe M. Campeau, Katherine Agre, Vernon R. Sutton, Kirsty McWalter, Bertrand Isidor, Øystein L. Holla, Anna Lehman, Megha Desai, Jonathan Berg, Stéphane Bézieau, Rolph Pfundt, Jennifer Tarpinian, Jennifer B. Humberson, Holly A.F. Stessman, Madeleine R. Geisheker, Emma Bedoukian, Shalini N. Jhangiani, Marine I. Murphree, Annapurna Poduri, Anne-Sophie Denommé-Pichon, Christian Gilissen, Yaping Yang, Eliane Beauregard-Lacroix, Claude Férec, Francesca Filippini, Anne Guimier, Daryl A. Scott, Stephen Sanders, Julie C. Sapp, Ralitza H. Gavrilova, Slavé Petrovski, Ann Nordgren, Sylvia Redon, Ernie M.H.F. Bongers, Shelagh Joss, Jill A. Rosenfeld, Wallid Deb, Ingrid M. Wentzensen, Usha Kini, Vandana Shashi, Mindy H. Li, Stanislas Lyonnet, Thomas Garcia, Øyvind L. Busk, Christoffer Nellåker, Amber Begtrup, Brigitte Gilbert-Dussardier, Thomas Besnard, Francois V. Bolduc, Patrick R. Blackburn, Justine Rousseau, Frédéric Bilan, Eric W. Klee, Christopher T. Gordon, Pavel N. Pichurin, Peggy Kulch, Kevin P. Lally, Laurie Robak, Arnaud Picard, Kristian Tveten, Meredith Park, Sébastien Küry, Jaya Punetha, Moira Blyth, Asbjørg Stray-Pedersen, Jacqueline Harris, Erin L. Heinzen, Nicholas Stong, Cara M. Skraban, Julie S. Cohen, Aida Telegrafi, Xenia Latypova, Zeynep Coban Akdemir, Jacob Zyskind, Caitlin Troyer, Xiang-Jiao Yang, Tuula Rinne, Leslie G. Biesecker, Jennifer E. Posey, Kyle Retterer, Jeanne Amiel, Rui Xiao, Magnus Nordenskjöld, Tammie Dewan, Jennifer A. Sullivan, Charlotte von der Lippe, Evan E. Eichler, Anna Lindstrand, Dominique Bonneau, Yuri A. Zarate, Elaine H. Zackai, Fayth M. Kalb, Daniel H. Lowenstein, Shiri Avni, Benjamin Cogné, Jennifer J. Johnston, Kerri H. Whitlock, Catherine Shain, Séverine Audebert-Bellanger, Malin Kvarnung, Oana Caluseriu, David Goldstein, Annick Toutain, Andres Hernandez-Garcia, Brina Daniels, Sophie Ehresmann, James R. Lupski, Julie McGaughran, Ashley H Ebanks, Kévin Uguen, Marine Legendre, Sylvie Odent, Richard Redon, Erica H. Gerkes, Xiaofei Song, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Sainte Justine [Montréal], Université du Québec à Montréal = University of Québec in Montréal (UQAM), University of Oxford [Oxford], GeneDx [Gaithersburg, MD, USA], Mayo Clinic [Rochester], University of California [San Francisco] (UCSF), University of California, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement Français du Sang Bretagne, EFS, Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Johns Hopkins University School of Medicine [Baltimore], Kennedy Krieger Institute [Baltimore], Chapel Allerton Hospital, University of British Columbia (UBC), University of Dundee, Rush University Medical Center [Chicago], Oxford University Hospitals NHS Trust, Queen Elizabeth University Hospital (Glasgow), Trondheim University, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), University of Virginia [Charlottesville], Texas Children's Hospital [Houston, USA], Baylor College of Medicine (BCM), Baylor University, University of Pennsylvania [Philadelphia], National Human Genome Research Institute (NHGRI), Harvard Medical School [Boston] (HMS), Karolinska University Hospital [Stockholm], Duke University Medical Center, University of Groningen [Groningen], University of Arkansas for Medical Sciences (UAMS), McGovern Medical School [Houston, Texas], The University of Texas Health Science Center at Houston (UTHealth), Phoenix Children's Hospital, Columbia University [New York], University of Southern Queensland (USQ), Telemark Hospital Trust [Skien, Norway], University of Washington [Seattle], Oslo University Hospital [Oslo], Children’s Hospital of Philadelphia (CHOP ), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Radboud University Medical Center [Nijmegen], Ann & Robert H. Lurie Children's Hospital of Chicago, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Pontchaillou [Rennes], Centre de référence Maladies Rares CLAD-Ouest [Rennes], 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 Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre hospitalier universitaire de Poitiers (CHU Poitiers), University of Alberta, Boston Children's Hospital, McGill University Health Center [Montreal] (MUHC), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Creighton University Medical School [Omaha, NE, USA], Howard Hughes Medical Institute [Boston] (HHMI), Howard Hughes Medical Institute (HHMI)-Harvard Medical School [Boston] (HMS), National Institute of Neurological Disorders and Stroke, K08 HG008986, National Human Genome Research Institute, BC Children’s Hospital Foundation, Genome British Columbia, Fonds de Recherche du Québec - Santé, Canadian Institutes of Health Research, Center for Individualized Medicine, Mayo Clinic, Health Regional Agency from Poitou-Charentes, French Ministry of Health, RC14_0107, HUGODIMS, NS053998, The Epilepsy Phenome/Genome Project, NS077303, Epi4K, Duke Genome Sequencing Clinic, NINDS R35 NS105078, National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development, HG200328 12, intramural research program of the NHGRI, Dart NeuroScience, Kids Brain Health Network, Mining for Miracles, UM1 HG006542, National Heart, Lung, and Blood Institute, CIM Investigative and Functional Genomics Program, R01MH101221, National Institute of Mental Health, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), University of Oxford, University of California [San Francisco] (UC San Francisco), University of California (UC), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), University of Virginia, University of Pennsylvania, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), CCSD, Accord Elsevier, Faculteit Medische Wetenschappen/UMCG, Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: CHROMATIN, Male, 0301 basic medicine, Autism, Sequence Homology, [SDV.GEN] Life Sciences [q-bio]/Genetics, Medical and Health Sciences, 0302 clinical medicine, SCHIZOPHRENIA, Gene expression, 2.1 Biological and endogenous factors, Missense mutation, Aetiology, Child, de novo variants, Genetics (clinical), Pediatric, Genetics & Heredity, Genetics, biology, neurodevelopmental disorders, histone acetylation, Adaptor Proteins, Nuclear Proteins, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], Syndrome, Biological Sciences, Prognosis, Phenotype, Chromatin, Mental Health, Histone, intellectual disability, Child, Preschool, Female, REGULATOR, congenital malformations, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], BRAIN-DEVELOPMENT, Adult, Adolescent, Histone acetyltransferase complex, Intellectual and Developmental Disabilities (IDD), Mutation, Missense, Deciphering Developmental Disorders study, autism spectrum disorder, KAT6B, RNAI SCREEN, Young Adult, 03 medical and health sciences, CAUSES Study, Rare Diseases, Intellectual Disability, Report, COFACTOR, medicine, RUBINSTEIN-TAYBI-SYNDROME, Humans, Amino Acid Sequence, Autistic Disorder, Preschool, Gene, Genetic Association Studies, Adaptor Proteins, Signal Transducing, [SDV.GEN]Life Sciences [q-bio]/Genetics, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Rubinstein–Taybi syndrome, Signal Transducing, Neurosciences, Infant, medicine.disease, TRRAP, Brain Disorders, SELF-RENEWAL, 030104 developmental biology, DE-NOVO MUTATIONS, Mutation, biology.protein, Missense, 030217 neurology & neurosurgery
Abstract: Contains fulltext : 202928.pdf (Publisher’s version ) (Open Access) Acetylation of the lysine residues in histones and other DNA-binding proteins plays a major role in regulation of eukaryotic gene expression. This process is controlled by histone acetyltransferases (HATs/KATs) found in multiprotein complexes that are recruited to chromatin by the scaffolding subunit transformation/transcription domain-associated protein (TRRAP). TRRAP is evolutionarily conserved and is among the top five genes intolerant to missense variation. Through an international collaboration, 17 distinct de novo or apparently de novo variants were identified in TRRAP in 24 individuals. A strong genotype-phenotype correlation was observed with two distinct clinical spectra. The first is a complex, multi-systemic syndrome associated with various malformations of the brain, heart, kidneys, and genitourinary system and characterized by a wide range of intellectual functioning; a number of affected individuals have intellectual disability (ID) and markedly impaired basic life functions. Individuals with this phenotype had missense variants clustering around the c.3127G>A p.(Ala1043Thr) variant identified in five individuals. The second spectrum manifested with autism spectrum disorder (ASD) and/or ID and epilepsy. Facial dysmorphism was seen in both groups and included upslanted palpebral fissures, epicanthus, telecanthus, a wide nasal bridge and ridge, a broad and smooth philtrum, and a thin upper lip. RNA sequencing analysis of skin fibroblasts derived from affected individuals skin fibroblasts showed significant changes in the expression of several genes implicated in neuronal function and ion transport. Thus, we describe here the clinical spectrum associated with TRRAP pathogenic missense variants, and we suggest a genotype-phenotype correlation useful for clinical evaluation of the pathogenicity of the variants.
Published: 2019
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22. First-line pembrolizumab with or without platinum doublet chemotherapy in non-small-cell lung cancer patients with PD-L1 expression ≥50%

Author: Gilles Robinet, Christos Chouaid, Radj Gervais, Roland Schott, Florian Guisier, Chantal Decroisette, Jean-Bernard Auliac, Olivier Bylicki, Charles Ricordel, Laurent Greillier, Maurice Pérol, Benjamin Besse, Renaud Descourt, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Service de Pneumologie [CHI Créteil], CHI Créteil, IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Léon Bérard [Lyon], Institut Gustave Roussy (IGR), Université Paris-Saclay, Département de médecine oncologique [Gustave Roussy], Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Hôpital d'Instruction des Armées Sainte Anne, Service de Santé des Armées, CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Paul Strauss, CRLCC Paul Strauss, Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], and Hôpital Charles Nicolle [Rouen]-CHU Rouen
Subjects: Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Lung Neoplasms, First line, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pembrolizumab, Antibodies, Monoclonal, Humanized, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, B7-H1 Antigen, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Carcinoma, Non-Small-Cell Lung, PD-L1, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Multicenter Studies as Topic, Medicine, Prospective Studies, 030212 general & internal medicine, Lung cancer, Lung, Response Evaluation Criteria in Solid Tumors, Randomized Controlled Trials as Topic, Chemotherapy, biology, business.industry, General Medicine, Middle Aged, medicine.disease, Progression-Free Survival, Clinical trial, Clinical Trials, Phase III as Topic, 030220 oncology & carcinogenesis, Disease Progression, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Pd l1 expression, business, Follow-Up Studies
Abstract: Pembrolizumab plus chemotherapy is currently used in the first-line treatment of advanced non-small-cell lung cancer withoutLay abstract Non-small-cell lung cancer (NSCLC) is the most frequent type of lung cancer. Most NSCLC patients are diagnosed with advanced disease and only 10–15% of them are alive after 5 years. In the absence of specific tumor mutations, the currently recommended treatment is a combination of chemotherapy and immunotherapy with the monoclonal antibody pembrolizumab. The goal of immunotherapy is to prevent cancer from evading the immune system by interacting with molecules expressed at the surface of tumor cells (PD-L1) or immune cells (PD-1). A study comparing chemotherapy plus pembrolizumab versus pembrolizumab alone has never been performed in patients with a high level of PD-L1 expression on tumor cells. Therefore we designed the PERSEE study to compare these treatments in advanced-stage NSCLC patients with PD-L1 expression on ≥50% of tumor cells.
Published: 2021
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23. Knowledge and Opinions of French Dental Students Toward Occlusal and Proximal Restorative Thresholds

Author: Gasqui, Marie-Agnès, Laforest, Laurent, Le Clerc, Justine, Ceinos, Romain, Chemla, Florence, Chevalier, Valérie, Colon, Pierre, Fioretti, Florence, Gevrey, Alexis, Kérourédan, Olivia, Maret, Delphine, Mocquot, Caroline, Özcan, Canan, Pelissier, Bruno, Perez, Fabienne, Terrer, Elodie, Turpin, Yann-Loïg, Arbab-Chirani, Reza, Doméjean, Sophie, Seux, Dominique, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Université de Rennes 1 - UFR d'Odontologie (UR1 Odontologie), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université Côte d'Azur - Faculté de Chirurgie Dentaire (UCA Faculté Odontologie), Université Côte d'Azur (UCA), Hôpital Saint-Roch [Nice], Aix-Marseille Université - Faculté des sciences médicales et paramédicales (AMU SMPM), Aix Marseille Université (AMU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Bretagne Occidentale - UFR Odontologie (UBO UFR Odontologie), Université de Brest (UBO), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Université Claude Bernard Lyon 1 - Faculté des sciences et technologies (UCBL FST), Université de Lyon-Université de Lyon, Université de Strasbourg (UNISTRA), Faculté d'odontologie [Nancy], Université de Lorraine (UL), Université de Bordeaux (UB), Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Centre d'anthropologie et de génomique de Toulouse (CAGT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université de Reims Champagne-Ardenne (URCA), Faculté d'odontologie [Montpellier], Université de Montpellier (UM), Regenerative Medicine and Skeleton research lab (RMeS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Nantes - UFR Odontologie, Université de Nantes (UN), Service des Maladies Infectieuses et Tropicales [CHU Hôpital Nord - Marseille] (M.I.T), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Centre de Recherche en Odontologie Clinique (CROC), Université Clermont Auvergne (UCA), CHU Clermont-Ferrand, Eschevins, Caroline, Université de Rennes (UR), Laboratoire de Bioingénierie et NanoSciences (LBN), Regenerative Medicine and Skeleton (RMeS), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université de Rennes - UFR d'Odontologie (UR Odontologie), Université Claude Bernard Lyon 1 - Faculté des sciences (UCBL FS), Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and Université de Nantes - UFR Odontologie (UFR Odonto)
Subjects: minimal intervention, MESH: Humans, MESH: Dentin, MESH: Dental Restoration, Permanent, Students, Dental, dental students, MESH: Dental Caries, Dental Caries, dental education, MESH: Cross-Sectional Studies, Cross-Sectional Studies, carious lesions, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Dentin, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, restorative threshold, MESH: Students, Dental, Dental Restoration, Permanent
Abstract: To investigate the practices, knowledge and opinions of French dental students (FDSs) in various domains of minimal intervention (MI) in cariology.A cross-sectional, questionnaire-based study was conducted in spring 2018 among all fifth-year French dental students (FDSs) from the 16 French dental schools. The present article focuses on restorative management. Statistical analyses (descriptive, chi-squared) were performed.The response rate was 84.5%. Overall, 97.4% of respondents would have operatively intervened for proximal and 83% for occlusal carious lesions, respectively, while non-or micro-invasive intervention would have been possible. Interestingly, 15% would completely open the occlusal fissures. For both occlusal and proximal lesions requiring a restoration, composite resin was indicated by over 95% of the respondents. In a clinical case, 51.6% of FDSs who rightly diagnosed an enamel carious lesion would operatively intervene. When FDSs could not diagnose the type of carious lesions, a high proportion of invasive actions were also reported (40%). FDSs who read scientific articles were more likely to consider the high importance of not filling sound teeth unnecessarily (p = 0.033).FDSs do not have sufficient awareness of MI guidelines regarding occlusal and proximal restorative thresholds. Efforts are required in dental schools to teach FDSs to postpone invasive/restorative strategies to later stages of carious progression. There is a need to strengthen prevention techniques and non-invasive options in the teaching of MI in cariology.
Published: 2021
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24. Synthetic alkyl-ether-lipid promotes TRPV2 channel trafficking trough PI3K/Akt-girdin axis in cancer cells and increases mammary tumour volume

Author: Audrey Gambade, Marie Potier-Cartereau, Yann Fourbon, Philippe Bougnoux, Romain Félix, Sana Kouba, David Ternant, François Carreaux, Maxime Guéguinou, Ana Bouchet, Paul-Alain Jaffrès, Thomas Harnois, Christophe Vandier, Olivier Mignen, Aurélie Chantôme, Christophe Arnoult, Jean-Pierre Haelters, Thibauld Oullier, Séverine Marionneau-Lambot, Aubin Penna, Günther Weber, Gaëlle Simon, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), Institut de Recherche en Santé de l'Université de Nantes (IRS-UN), The Enteric Nervous System in gut and brain disorders [U1235] (TENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Brest (UBO), Chimie, Electrochimie Moléculaires et Chimie Analytique (CEMCA), Université de Brest (UBO)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Brestois Santé Agro Matière (IBSAM), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Inserm UMR 1227 Immunothérapies et Pathologies Lymphocytaires B, Hôpital Morvan - CHRU de Brest (CHU - BREST ), INCa, Ligue Nationale Contre le Cancer, Region Centre Val de Loire (LIPIDS project of ARD2020-Biomédicaments), INSERM, Cancéropôle Grand Ouest, the association 'CANCEN' and Tours Hospital oncology association 'ACORT'. M. Guéguinou, Y. Fourbon and A. Gambade held fellowships from the 'Region Centre', 'Ministère de l'Enseignement Supérieur et de la Recherche'., Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours, and Université de Poitiers-Université de Tours-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Physiology, [SDV]Life Sciences [q-bio], Metastasis, 03 medical and health sciences, Transient receptor potential channel, chemistry.chemical_compound, 0302 clinical medicine, medicine, [CHIM]Chemical Sciences, Molecular Biology, Protein kinase B, PI3K/AKT/mTOR pathway, Constitutive Ca2+ entry, Chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Breast cancer cell migration, Cancer, Cell migration, Cell Biology, medicine.disease, 3. Good health, Cell biology, TRPV2, 030104 developmental biology, Cancer cell, lipids (amino acids, peptides, and proteins), Alkyl-ether-lipid, 030217 neurology & neurosurgery, Edelfosine
Abstract: International audience; The Transient Receptor Potential Vanilloid type 2 (TRPV2) channel is highly selective for Ca2+ and can be activated by lipids, such as LysoPhosphatidylCholine (LPC). LPC analogues, such as the synthetic alkyl-ether-lipid edelfosine or the endogenous alkyl-ether-lipid Platelet Activating Factor (PAF), modulates ion channels in cancer cells. This opens the way to develop alkyl-ether-lipids for the modulation of TRPV2 in cancer. Here, we investigated the role of 2-Acetamido-2-Deoxy-l-O-Hexadecyl-rac-Glycero-3-PhosphatidylCholine (AD-HGPC), a new alkyl-ether-lipid (LPC analogue), on TRPV2 trafficking and its impact on Ca2+ -dependent cell migration. The effect of AD-HGPC on the TRPV2 channel and tumour process was further investigated using calcium imaging and an in vivo mouse model. Using molecular and pharmacological approaches, we dissected the mechanism implicated in alkyl-ether-lipids sensitive TRPV2 trafficking. We found that TRPV2 promotes constitutive Ca2+ entry, leading to migration of highly metastatic breast cancer cell lines through the PI3K/Akt-Girdin axis. AD-HGPC addresses the functional TRPV2 channel in the plasma membrane through Golgi stimulation and PI3K/Akt/Rac-dependent cytoskeletal reorganization, leading to constitutive Ca2+ entry and breast cancer cell migration (without affecting the development of metastasis), in a mouse model. We describe, for the first time, the biological role of a new alkyl-ether-lipid on TRPV2 channel trafficking in breast cancer cells and highlight the potential modulation of TRPV2 by alkyl-ether-lipids as a novel avenue for research in the treatment of metastatic cancer.
Published: 2021
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25. Severe phenotype in patients with large deletions of NF1

Author: Laurence, Pacot, Dominique, Vidaud, Audrey, Sabbagh, Ingrid, Laurendeau, Audrey, Briand-Suleau, Audrey, Coustier, Théodora, Maillard, Cécile, Barbance, Fanny, Morice-Picard, Sabine, Sigaudy, Olga O, Glazunova, Lena, Damaj, Valérie, Layet, Chloé, Quelin, Brigitte, Gilbert-Dussardier, Frédérique, Audic, Hélène, Dollfus, Anne-Marie, Guerrot, James, Lespinasse, Sophie, Julia, Marie-Christine, Vantyghem, Magali, Drouard, Marilyn, Lackmy, Bruno, Leheup, Yves, Alembik, Alexia, Lemaire, Patrick, Nitschké, Florence, Petit, Anne, Dieux Coeslier, Eugénie, Mutez, Alain, Taieb, Mélanie, Fradin, Yline, Capri, Hala, Nasser, Lyse, Ruaud, Benjamin, Dauriat, Sylvie, Bourthoumieu, David, Geneviève, Séverine, Audebert-Bellanger, Mathilde, Nizon, Radka, Stoeva, Geoffroy, Hickman, Gaël, Nicolas, Juliette, Mazereeuw-Hautier, Arnaud, Jannic, Salah, Ferkal, Béatrice, Parfait, Michel, Vidaud, Members Of The Nf France Network, Pierre, Wolkenstein, Eric, Pasmant, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Cancer Research and Personalized Medicine - CARPEM [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-CHU Necker - Enfants Malades [AP-HP], GHU AP-HP Centre Université de Paris, Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université de Paris (UP), Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Pontchaillou [Rennes], Groupe Hospitalier du Havre, Centre de référence Maladies Rares CLAD-Ouest [Rennes], Hôpital Sud [CHU Rennes], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Laboratoire de Génétique Médicale (LGM), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), Centre Hospitalier Métropole Savoie [Chambéry], CHU Toulouse [Toulouse], Hôpital Purpan [Toulouse], 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), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, CHU Pointe-à-Pitre/Abymes [Guadeloupe], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital de Hautepierre [Strasbourg], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CHU Lille, Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Bordeaux [Bordeaux], Hôpital Robert Debré, Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), CHU Limoges, Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Le Mans (CH Le Mans), Hopital Saint-Louis [AP-HP] (AP-HP), Université de Rouen Normandie (UNIROUEN), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Centre d'Investigation Clinique Henri Mondor (CIC Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), This work was supported by grants by Association Neurofibromatoses et Recklinghausen Fondation CAP NF, Ligue Française Contre les Neurofibromatoses, INSERM (Nf1GeneModif project), and Ministère de l’Enseignement Supérieur et de la Recherche., Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), 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)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 261), Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Lille Neurosciences & Cognition - U 1172 (LilNCog), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Admin, Oskar
Subjects: Genotype-phenotype correlation, congenital, hereditary, and neonatal diseases and abnormalities, cardiovascular abnormalities, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, dysmorphism, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, skeletal abnormalities, neurofibromatosis type 1, Article, [SDV.CAN] Life Sciences [q-bio]/Cancer, MPNSTs, learning disabilities, Neurofi-bromas, neoplasms, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, NF1 deletion, genotype–phenotype correlation, eye diseases, nervous system diseases, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, NF1, neurofibromas, NFs, malignant peripheral nerve sheath tumors, tumor predisposition
Abstract: Simple Summary Neurofibromatosis type 1 (NF1) is a genetic disorder caused by pathogenic variants in the NF1 tumor suppressor gene. In 5–10% of NF1 patients, a large heterozygous deletion of the whole NF1 gene is identified, leading to the commonly called “NF1 microdeletion syndrome”. NF1-deleted patients were previously reported to develop a particularly severe form of the disease with frequent cognitive impairment and an increased risk of benign and malignant tumors. Here, we performed a comprehensive clinical assessment of the largest NF1-deleted cohort to date, including 126 NF1 patients with a deletion of the NF1 gene. This work provides new insights into the specific phenotype associated with NF1 deletions and may contribute to improve the follow-up care of NF1 patients. Abstract Complete deletion of the NF1 gene is identified in 5–10% of patients with neurofibromatosis type 1 (NF1). Several studies have previously described particularly severe forms of the disease in NF1 patients with deletion of the NF1 locus, but comprehensive descriptions of large cohorts are still missing to fully characterize this contiguous gene syndrome. NF1-deleted patients were enrolled and phenotypically characterized with a standardized questionnaire between 2005 and 2020 from a large French NF1 cohort. Statistical analyses for main NF1-associated symptoms were performed versus an NF1 reference population. A deletion of the NF1 gene was detected in 4% (139/3479) of molecularly confirmed NF1 index cases. The median age of the group at clinical investigations was 21 years old. A comprehensive clinical assessment showed that 93% (116/126) of NF1-deleted patients fulfilled the NIH criteria for NF1. More than half had café-au-lait spots, skinfold freckling, Lisch nodules, neurofibromas, neurological abnormalities, and cognitive impairment or learning disabilities. Comparison with previously described “classic” NF1 cohorts showed a significantly higher proportion of symptomatic spinal neurofibromas, dysmorphism, learning disabilities, malignancies, and skeletal and cardiovascular abnormalities in the NF1-deleted group. We described the largest NF1-deleted cohort to date and clarified the more severe phenotype observed in these patients.
Published: 2021
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26. Brief Report on the Efficacy of Nivolumab in Patients With Previously Treated Advanced Large-Cell Neuroendocrine Cancer of the Lung

Author: Agar, Camille, Geier, Margaux, Léveiller, Guillaume, Lamy, Régine, Bizec, Jean-Louis, Tiercin, Marie, Bernier, Cyril, Robinet, Gilles, Léna, Hervé, Ricordel, Charles, Corre, Romain, CHU Pontchaillou [Rennes], Hôpital Morvan - CHRU de Brest (CHU - BREST ), Centre Hospitalier Yves le Foll, Groupe Hospitalier Bretagne Sud (GHBS), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), CH de Saint-Malo [Broussais], Centre hospitalier Rene Pleven de Dinan, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Centre Hospitalier Intercommunal de Cornouaille (CHIC), Roche, Merck Sharp and Dohme, Bristol-Myers Squibb, AstraZeneca, Jonchère, Laurent, Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Immune checkpoint inhibitors, Large-cell neuroendocrine cancer, Nivolumab, [SDV.CAN] Life Sciences [q-bio]/Cancer, Brief Report, [SDV.CAN]Life Sciences [q-bio]/Cancer, Lung cancer
Abstract: International audience; INTRODUCTION: The optimal management of large cell neuroendocrine cancer of the lung (LCNEC) is unclear, and data regarding anti-programmed cell death protein 1 (PD-1) antibodies are scarce. This study reports the clinical efficacy of a PD-1 inhibitor in patients with advanced LCNEC. METHODS: All patients with stage III to IV LCNEC treated with at least one previous cycle of chemotherapy between January 1, 2015 and December 31, 2018 were reviewed retrospectively. Patients were divided into two groups depending on their exposure to nivolumab as second-line treatment or beyond. The primary objective was to assess nivolumab’s efficacy. RESULTS: A total of 51 patients with advanced LCNEC from eight centers were analyzed, including 17 who received nivolumab. The PD-1 inhibitor was used as second-line treatment in 77% of cases, with a median number of eight doses (range: 1-62). After nivolumab treatment, the median overall survival was 12.1 months (95% confidence interval [CI]: 7.10-14.20). The objective response rate was 29.4% (95% CI: 10.3-56.0), and median progression-free survival was 3.9 months (95% CI: 1.68-7.17). The programmed death-ligand 1 status was unknown. There was no difference in the efficacy of first-line chemotherapy; the objective response rate was 23.5% (n = four of 17) in the nivolumab group versus 32.4% (n = 11 of 34) in the conventional treatment group, and progression-free survival was 3.5 months (95% CI: 1.7-4.4) versus 2.1 months (95% CI: 1.4-4.2), respectively. CONCLUSIONS: In a real-world setting, nivolumab seems to be an effective second-line treatment in patients with advanced LCNEC. Large prospective studies in this setting are still required.
Published: 2021
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27. Molecular classification and prognosis in younger adults with acute myeloid leukemia and intermediate-risk cytogenetics treated or not by gemtuzumab ozogamycin: Final results of the GOELAMS/FILO acute myeloid leukemia 2006-intermediate-risk trial

Author: Norbert Ifrah, Hacene Zerazhi, Pierre-Yves Dumas, Norbert Vey, Isabelle Luquet, Denis Caillot, Marie-Christine Béné, Célestine Simand, Marie-Pierre Ledoux, Véronique Dorvaux, Yosr Hicheri, Anne Banos, Maria Pilar Gallego Hernanz, Chantal Himberlin, Odile Blanchet, Eric Delabesse, Catherine Humbrecht, Pascal Turlure, Arnaud Pigneux, Eric Jourdan, Jacques Delaunay, Didier Bouscary, Emmanuelle Tavernier, Christian Recher, Gaelle Guillerm, Mathilde Hunault-Berger, Romain Guieze, Martin Carre, Anne Bouvier, Jean-Pierre Marolleau, Claude Eric Bulabois, Pascale Cornillet-Lefebvre, Mario Ojeda-Uribe, Marc Bernard, Magda Alexis, Jean-François Hamel, Etienne Daguindau, Pierre Peterlin, Gabrielle Roth Guepin, Emmanuel Gyan, Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), 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)-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), 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 ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital privé du Confluent [Nantes], 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Bordeaux, Service d'Hématologie Clinique et Thérapie Cellulaire, F-33000 Bordeaux, France., Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Cancérologie de Strasbourg Europe (ICANS), Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire [Grenoble] (CHU), Service d'Hématologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne (UCA), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Reims (CHU Reims), Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] (FHU GOAL), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service des maladies du sang [Angers], CHU Pontchaillou [Rennes], Département d'Hématologie [CHU Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier de la Côte Basque (CHCB), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional d'Orléans (CHRO), 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), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre Hospitalier Henri Duffaut (Avignon), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Ressources Biologiques [CHU Angers], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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], Service d'Hématologie Biologique [Hôpital Robert Debré, Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Oncology, Adult, Male, Risk, medicine.medical_specialty, NPM1, Adolescent, medicine.medical_treatment, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, Phases of clinical research, Gene mutation, Disease-Free Survival, Cytogenetics, Young Adult, Internal medicine, hemic and lymphatic diseases, CEBPA, Medicine, Cluster Analysis, Humans, Chemotherapy, business.industry, Gene Expression Regulation, Leukemic, Gene Expression Profiling, Remission Induction, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Hematology, General Medicine, Middle Aged, Prognosis, Gemtuzumab, Transplantation, Leukemia, Myeloid, Acute, Karyotyping, Cytogenetic Analysis, Mutation, Female, business
Abstract: International audience; In this randomized phase 3 study, the FILO group tested whether the addition of 6 mg/m(2) of gemtuzumab ozogamycin (GO) to standard chemotherapy could improve outcome of younger patients with de novo acute myeloid leukemia (AML) and intermediate-risk cytogenetics. GO arm was prematurely closed after 254 inclusions because of toxicity. A similar complete remission rate was observed in both arms. Neither event-free survival nor overall survival were improved by GO in younger AML patients (
Published: 2021
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28. Inherited human Apollo deficiency causes severe bone marrow failure and developmental defects

Author: Laëtitia Kermasson, Dmitri Churikov, Aya Awad, Riham Smoom, Elodie Lainey, Fabien Touzot, Séverine Audebert-Bellanger, Sophie Haro, Lauréline Roger, Emilia Costa, Maload Mouf, Adriana Bottero, Matias Oleastro, Chrystelle Abdo, Jean-Pierre de Villartay, Vincent Géli, Yehuda Tzfati, Isabelle Callebaut, Silvia Danielian, Gabriela Soares, Caroline Kannengiesser, Patrick Revy, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Alexander Silberman Institute of Life Science, The Hebrew University of Jerusalem (HUJ), Hôpital Robert Debré, CHU Sainte Justine [Montréal], Hôpital Morvan - CHRU de Brest (CHU - BREST ), Muséum national d'Histoire naturelle (MNHN), Centro Hospitalar Universitário do Porto, Hospital Nacional de Pediatría Prof. Dr Juan P. Garrahan [Buenos Aires], Hospital Nacional de Pediatría J.P. Garrahan, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Institut de recherche pour le développement [IRD] : UR206-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), 'Juan Pedro Garrahan' National Hospital of Pediatrics, Buenos Aires, Centro de Genética Jacinto Magalhães [Porto], Hospital de São João [Porto], AP-HP - Hôpital Bichat - Claude Bernard [Paris], and ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018)
Subjects: Fetal Growth Retardation, [SDV]Life Sciences [q-bio], Intellectual Disability, Immunology, Mutation, Microcephaly, Humans, Cell Biology, Hematology, Telomere, Biochemistry, Dyskeratosis Congenita
Abstract: Inherited bone marrow failure syndromes (IBMFSs) are a group of disorders typified by impaired production of 1 or several blood cell types. The telomere biology disorders dyskeratosis congenita (DC) and its severe variant, Høyeraal-Hreidarsson (HH) syndrome, are rare IBMFSs characterized by bone marrow failure, developmental defects, and various premature aging complications associated with critically short telomeres. We identified biallelic variants in the gene encoding the 5′-to-3′ DNA exonuclease Apollo/SNM1B in 3 unrelated patients presenting with a DC/HH phenotype consisting of early-onset hypocellular bone marrow failure, B and NK lymphopenia, developmental anomalies, microcephaly, and/or intrauterine growth retardation. All 3 patients carry a homozygous or compound heterozygous (in combination with a null allele) missense variant affecting the same residue L142 (L142F or L142S) located in the catalytic domain of Apollo. Apollo-deficient cells from patients exhibited spontaneous chromosome instability and impaired DNA repair that was complemented by CRISPR/Cas9-mediated gene correction. Furthermore, patients’ cells showed signs of telomere fragility that were not associated with global reduction of telomere length. Unlike patients’ cells, human Apollo KO HT1080 cell lines showed strong telomere dysfunction accompanied by excessive telomere shortening, suggesting that the L142S and L142F Apollo variants are hypomorphic. Collectively, these findings define human Apollo as a genome caretaker and identify biallelic Apollo variants as a genetic cause of a hitherto unrecognized severe IBMFS that combines clinical hallmarks of DC/HH with normal telomere length.
Published: 2021
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29. A new molecular classification to drive precision treatment strategies in primary Sjögren's syndrome

Author: Soret, Perrine, Le Dantec, Christelle, Desvaux, Emiko, Foulquier, Nathan, Chassagnol, Bastien, Hubert, Sandra, Jamin, Christophe, Barturen, Guillermo, Desachy, Guillaume, Devauchelle-Pensec, Valérie, Boudjeniba, Cheïma, Cornec, Divi, Saraux, Alain, Jousse-Joulin, Sandrine, Barbarroja, Nuria, Rodríguez-Pintó, Ignasi, De Langhe, Ellen, Beretta, Lorenzo, Chizzolini, Carlo, Kovács, László, Witte, Torsten, Bettacchioli, Eléonore, Buttgereit, Anne, Makowska, Zuzanna, Lesche, Ralf, Borghi, Maria Orietta, Martin, Javier, Courtade-Gaiani, Sophie, Xuereb, Laura, Guedj, Mickaël, Moingeon, Philippe, Alarcón-Riquelme, Marta, Laigle, Laurence, Pers, Jacques-Olivier, Vigone, Barbara, Lauwerys, Bernard, Maudoux, Anne-Lise, Vasconcelos, Carlos, Tavares, Ana, Faria, Raquel, Brandão, Mariana, Campar, Ana, Marinho, António, Farinha, Fátima, Almeida, Isabel, Gonzalez-Gay Mantecón, Miguel Angel, Blanco Alonso, Ricardo, Corrales Martínez, Alfonso, Cervera, Ricard, Espinosa, Gerard, Lories, Rik, Hunzelmann, Nicolas, Belz, Doreen, Baerlecken, Niklas, Stummvoll, Georg, Zauner, Michael, Lehner, Michaela, Collantes, Eduardo, Ortega-Castro, Rafaela, Aguirre-Zamorano, Ma Angeles, Escudero-Contreras, Alejandro, Castro-Villegas, Ma Carmen, Jiménez Gómez, Yolanda, Ortego, Norberto, Fernández Roldán, María Concepción, Raya, Enrique, Jiménez Moleón, Inmaculada, de Ramon, Enrique, Díaz Quintero, Isabel, Meroni, Pier Luigi, Gerosa, Maria, Schioppo, Tommaso, Artusi, Carolina, Zuber, Aleksandra, Wynar, Donatienne, Balog, Attila, Deák, Magdolna, Bocskai, Márta, Dulic, Sonja, Kádár, Gabriella, Hiepe, Falk, Thiel, Silvia, Rodriguez Maresca, Manuel, López-Berrio, Antonio, Aguilar-Quesada, Rocío, Navarro-Linares, Héctor, Ioannou, Yiannis, Chamberlain, Chris, Marovac, Jacqueline, Alarcón Riquelme, Marta, Gomes Anjos, Tania, Marañón, Concepción, Le Lann, Lucas, Simon, Quentin, Rouvière, Bénédicte, Varela, Nieves, Muchmore, Brian, Dufour, Aleksandra, Alvarez, Montserrat, Cremer, Jonathan, Lopez-Pedrera, Chary, Gerl, Velia, Khodadadi, Laleh, Cheng, Qingyu, De Groof, Aurélie, Ducreux, Julie, Trombetta, Elena, Li, Tianlu, Alvarez-Errico, Damiana, Kniesch, Katja, Azevedo, Nancy, Neves, Esmeralda, Rao, Sambasiva, Jouve, Pierre-Emmanuel, Agence Nationale de la Recherche (France), European Commission, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Cluj-Napoca Unit-The Net-Work of International Francophone Clinical Epidemiology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca Unit-The Net-Work of International Francophone Clinical Epidemiology, Iuliu Hatieganu University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania., Iuliu Hatieganu University of Medicine & Pharmacy, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), University of South Florida [Tampa] (USF), Cluj-Napoca Unit-The Net-Work of International Francophone Clinical Epidemiology, Iuliu Hatieganu University of Medicine and Pharmacy, 400000 Cluj-Napoca, Romania., Institut de Recherches Internationales Servier [Suresnes] (IRIS), Centre for Genomics and Oncological Reearch (GENYO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Instituto Maimonides de Investigación Biomédica de Cordoba (IMIBIC), Universidad de Córdoba [Cordoba]-Hospital Universitario Reina Sofía, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University Hospitals Leuven and Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium, Maggiore Hospital, IRCCS Foundation, Milano, Department of Pathology and Immunology [Geneva, Switzerland], University of Geneva [Switzerland], University of Szeged [Szeged], Clinic for Immunology and Rhematology, Hannover Medical School, Hanover, Germany, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Pharmaceuticals Division Bayer Pharma Aktiengesellschaft, Università degli Studi di Milano [Milano] (UNIMI), Instituto de Parasitología y Biomedicina 'López-Neyra' (IPBLN), Consejo Superior de Investigaciones Científicas (CSIC), Centre for Genomics and Oncological Research (GENYO) Pfizer, University of Granada, and Università degli Studi di Milano and IRCCS Maggiore Policlinico Hospital, Mangiagalli and Regina Elena Foundation
Subjects: Male, Oncology, MESH: Inflammation, MESH: Flow Cytometry, Disease, DISEASE, 0302 clinical medicine, Molecular classification, Databases, Genetic, MESH: Interferons, Databases, Protein, MESH: Cytokines, MESH: Middle Aged, Molecular medicine, Malalties autoimmunitàries, MESH: Polymorphism, Single Nucleotide, ASSOCIATION, Flow Cytometry, Pathophysiology, 3. Good health, Multigene Family, Marcadors bioquímics, Cohort, Cytokines, Science & Technology - Other Topics, Epigenetics, cell cycle, MESH: Computational Biology, medicine.medical_specialty, Science, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, splicing, MESH: Cross-Sectional Studies, Rheumatology, MESH: Computer Simulation, Humans, Computer Simulation, RITUXIMAB, SIGNATURES, Autoantibodies, Science & Technology, MESH: Humans, MESH: Transcriptome, Computational Biology, MESH: Adult, DNA Methylation, Immune dysregulation, Epigenètica, Clinical trial, CLINICAL PHENOTYPES, Cross-Sectional Studies, 030104 developmental biology, MESH: Sjogren's Syndrome, MESH: Genome-Wide Association Study, chronic lymphocytic leukemia, MESH: Multigene Family, MESH: Female, Biomarkers, RESPONSES, 0301 basic medicine, Proteome, Autoimmune diseases, General Physics and Astronomy, medicine.disease_cause, Cohort Studies, Clinical trials, MESH: DNA Methylation, MESH: Autoantibodies, RNA-Seq, liquid chromatography-tandem mass spectrometry, MESH: Cohort Studies, MESH: Databases, Genetic, Multidisciplinary, Biochemical markers, Middle Aged, MESH: Chemokines, Multidisciplinary Sciences, MESH: Proteome, Sjogren's Syndrome, Assaigs clinics, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Chemokines, HYDROXYCHLOROQUINE, Adult, INTERFERON, MESH: Databases, Protein, MEDLINE, Polymorphism, Single Nucleotide, MECHANISMS, Internal medicine, cell cycle, chronic lymphocytic leukemia, liquid chromatography-tandem mass spectrometry, splicing, medicine, MESH: RNA-Seq, Inflammation, 030203 arthritis & rheumatology, business.industry, General Chemistry, EFFICACY, MESH: Male, MESH: Biomarkers, Interferons, Transcriptome, business, Assaigs clínics, Genome-Wide Association Study
Abstract: There is currently no approved treatment for primary Sjögren’s syndrome, a disease that primarily affects adult women. The difficulty in developing effective therapies is -in part- because of the heterogeneity in the clinical manifestation and pathophysiology of the disease. Finding common molecular signatures among patient subgroups could improve our understanding of disease etiology, and facilitate the development of targeted therapeutics. Here, we report, in a cross-sectional cohort, a molecular classification scheme for Sjögren’s syndrome patients based on the multi-omic profiling of whole blood samples from a European cohort of over 300 patients, and a similar number of age and gender-matched healthy volunteers. Using transcriptomic, genomic, epigenetic, cytokine expression and flow cytometry data, combined with clinical parameters, we identify four groups of patients with distinct patterns of immune dysregulation. The biomarkers we identify can be used by machine learning classifiers to sort future patients into subgroups, allowing the re-evaluation of response to treatments in clinical trials., Sjögren’s syndrome, a disease that primarily affects women, is poorly understood. Here, the authors combine data from a large cohort of patients and healthy controls to identify biomarkers that distinguish patient subgroups to improve our understanding of the disease and facilitate drug development.
Published: 2021
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30. Une approche pour regrouper des sujets atteints de cancers, sur la base des similarités des répartitions cellulaires au sein de leurs biopsies

Author: El Ouahidi, Yassine, Feller, Matis, Talagas, Matthieu, Pasdeloup, Bastien, Pasdeloup, Bastien, IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT), Laboratoire sur les interactions Epithéliums Neurones (LIEN), Université de Brest (UBO), CHRU de Brest - Département de dermatologie, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Département Logique des Usages, Sciences sociales et Sciences de l'Information (IMT Atlantique - LUSSI), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Equipe DECIDE (Lab-STICC_DECIDE), Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance (Lab-STICC), École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), and Institut Mines-Télécom [Paris] (IMT)-École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique)
Subjects: histogrammes, [INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG], distance de Wasserstein, [SDV.CAN] Life Sciences [q-bio]/Cancer, analyse de survie, [SDV.CAN]Life Sciences [q-bio]/Cancer, [INFO.INFO-LG] Computer Science [cs]/Machine Learning [cs.LG], Cancer, clustering
Abstract: Extended version in English: https://arxiv.org/abs/2007.00135, In this paper, we introduce a novel and interpretable methodology to cluster subjects suffering from cancer, based on features extracted from their biopsies. Contrary to existing approaches, we propose here to capture complex patterns in the repartitions of their cells using histograms, and compare subjects on the basis of these repartitions. We describe here our complete workflow, including creation of the database, cells segmentation and phenotyping, computation of complex features, choice of a distance function between features, clustering between subjects using that distance, and survival analysis of obtained clusters. We illustrate our approach on a database of hematoxylin and eosin (H&E)-stained tissues of subjects suffering from Stage I lung adenocarcinoma, where our results match existing knowledge in prognosis estimation with high confidence., Nous présentons une méthodologie interprétable pour regrouper des sujets souffrant de cancer, basée sur des attributs extraits d'images numériques de leurs biopsies. Nous proposons d'analyser des répartitions cellulaires à l'aide d'histogrammes, et de comparer les sujets via ceux-ci. Nous décrivons ici la méthodologie pour définir ces histogrammes et les exploiter à des fins de clustering. Nous illustrons notre approche sur une base de données de tissus colorés à l'hématoxyline et à l'éosine de sujets atteints d'un adénocarcinome pulmonaire de stade I, où nos résultats coincident avec les connaissances existantes en matière d'estimation du pronostic de survie, avec une confiance statistique élevée.
Published: 2021

31. Techniques d’inhalation chez l’enfant

Author: P. Cros and Hôpital Morvan - CHRU de Brest (CHU - BREST )
Subjects: 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, [SDV]Life Sciences [q-bio], 030212 general & internal medicine, 3. Good health
Abstract: Resume Les medicaments inhales representent une part essentielle des traitements administres en pneumologie. Quelle que soit l’application envisagee, la maitrise du systeme d’administration et de son utilisation joue un role majeur car elle determine la maniere dont le principe actif va se deposer dans les voies aeriennes et ainsi son efficacite. Le medecin (pneumologue, pediatre, medecin generaliste) doit donc savoir utiliser le systeme d’inhalation qu’il prescrit afin de le montrer a son patient, et ceci a chaque consultation.
Published: 2020
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32. A 60-Year-Old Woman With Recurrent Hemoptysis

Author: Margaux Geier, Gaël Picart, Lydie Khatchatourian, Francis Couturaud, Nicolas Bizien, Laura Samaison, Gilles Robinet, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), CCSD, Accord Elsevier, Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Centre Hospitalier Intercommunal de Cornouaille (CHIC), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)
Subjects: Pulmonary and Respiratory Medicine, Pediatrics, medicine.medical_specialty, [SDV]Life Sciences [q-bio], New episode, Case presentation, Critical Care and Intensive Care Medicine, Chest pain, 03 medical and health sciences, 0302 clinical medicine, medicine, Medical history, 030212 general & internal medicine, business.industry, Bacterial pneumonia, medicine.disease, respiratory tract diseases, 3. Good health, [SDV] Life Sciences [q-bio], Pneumonia, 030228 respiratory system, Sputum, General health, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract: International audience; A 60-year-old non-smoker white woman presented with a new episode of hemoptysis. She reported recurrent hemoptoic sputum in the past month. She had no relevant medical history, except presumed resolved bacterial pneumonia 1 year ago. She denied taking immunosuppressive treatment and was not exposed to lung irritants. She had not traveled recently. General health status was good. She denied fever, dyspnea, chest pain, and extra-pulmonary symptoms.
Published: 2020
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33. Salivary Glands and Periodontal Changes in a Population of Sjögren's and Sicca Syndrome Treated by Pilocarpine: A Pilot Study

Author: Valérie Devauchelle-Pensec, Sylvie Boisramé, Divi Cornec, Alain Saraux, Dewi Guellec, Sandrine Jousse-Joulin, Luc Bressollette, Thierry Marhadour, Jacques-Olivier Pers, Thibaud Depinoy, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Université de Bretagne Occidentale - UFR Odontologie (UBO UFR Odontologie), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Ultrasound Unit Department, Brest, Michel, Geneviève, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, and Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM)
Subjects: medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Population, Salivary glands, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, stomatognathic system, Oral administration, Major Salivary Gland, Internal medicine, Sicca syndrome, medicine, Immunology and Allergy, education, Original Research, Ultrasonography, 030203 arthritis & rheumatology, education.field_of_study, business.industry, Ultrasound, Pilocarpine, 030206 dentistry, Periodontium, 3. Good health, stomatognathic diseases, Sjögren’s syndrome, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, medicine.drug
Abstract: Introduction Oral administration of pilocarpine enhances salivary flow in sicca patients but its effect upstream on ultrasound (US) of salivary glands (SG) and downstream on periodontium remain unknown. Methods Sicca patients were prospectively included. Echostructural and vascularization of SG were assessed using B mode and pulsed Doppler (USPD). Vascularization of SG was measured using resistive index (RI) before and after stimulation by lemon juice. Echostructure (measure of glandular length in cm2, evaluation of parotid and submandibular glands parenchymal abnormalities) was assessed at baseline (M0) and after 3 months (M3) of treatment with pilocarpine. A dental consultation was performed at M0 and M3 to evaluate changes in unstimulated salivary flow (USSF), stimulated salivary flow (SSF), and periodontal parameters such as modified gingival index (Lobene), plaque index (Silness), bleeding index, pocket depth, and pH. Results Nineteen patients were included but only 11 received pilocarpine treatment for 3 months, as six stopped pilocarpine due to side effects and two were excluded for other causes. Among the 11 patients who completed the 3-month follow-up, five had primary Sjögren’s syndrome according to the American-European’s classification criteria. As expected, statistical differences were found concerning SSF (p = 0.018) and USSF (p = 0.027) between M0 and M3 while no statistical change in both SG echostructure and vascularization or periodontal evaluation was shown. Conclusions Pilocarpine improved SSF and USSF measurements in sicca syndrome but no ultrasonography of major salivary glands (SGUS) structural and vascular changes were detected as well as periodontal evaluation. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-020-00263-y.
Published: 2020
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34. Epidemiology of cutaneous involvement in Sjögren syndrome: Data from three French pSS populations (TEARS, ASSESS, diapSS)

Author: Raphaèle Seror, Laurent Misery, Philippe Dieudé, Eric Hachulla, Xavier Mariette, Gilles Hayem, Jacques-Eric Gottenberg, Camille Villon, Aleth Perdriger, Laure Orgeolet, Jean-Jacques Dubost, Divi Cornec, Jacques Morel, Pierre-Yves Hatron, Jean-Marie Berthelot, Vincent Goëb, Anne-Laure Fauchais, Valérie Devauchelle-Pensec, Véronique Le Guern, Sandrine Jousse-Joulin, Olivier Vittecoq, Claire Larroche, Alain Saraux, Anne-Marie Roguedas, CHRU de Brest - Département de dermatologie, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Service de dermatologie (Dermato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de rhumatologie [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Rhumatologie (Rhumato - 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), Service de Rhumatologie [CHU Gabriel-Montpied], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Médecine interne A et polyclinique médicale [CHU Limoges], CHU Limoges, Service de Rhumatologie - AMIENS (AMIENS - Rhumato), CHU Amiens-Picardie, Centre National de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Oust de France (CeRAINO), F-59000, Lille, Service de médecine interne [Avicenne], Hôpital Avicenne [AP-HP], Département de Rhumatologie (Rhumato - Ambroise Paré - PARIS), Centre Hospitalier Universitaire Ambroise Paré (CHU Ambroise Paré), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de rhumatologie [Rennes] = Rheumatology [Rennes], CHU Pontchaillou [Rennes], Unité thérapeutique d'immunologie clinique et des maladies ostéoarticulaires [Hôpital Lapeyronie, Montpellier], Hôpital Lapeyronie [Montpellier] (CHU), Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), and Centre National de Référence CERAINO, Service de Rhumatologie (Hôpital de la Cavale Blanche)
Subjects: medicine.medical_specialty, Visual analogue scale, Placebo, Severity of Illness Index, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, Dry skin, medicine, Prevalence, Humans, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Pain Measurement, 030203 arthritis & rheumatology, integumentary system, business.industry, Hypergammaglobulinemia, medicine.disease, Dermatology, eye diseases, 3. Good health, stomatognathic diseases, Sjogren's Syndrome, Cohort, Tears, [SDV.IMM]Life Sciences [q-bio]/Immunology, Rituximab, medicine.symptom, business, medicine.drug
Abstract: To determine the prevalence and significance of dermatological disorders in primary Sjögren syndrome (pSS).We used 2 pSS French cohorts (ASSESS, in which prevalence of skin disorders in 395 patients was evaluated; and diapSS, in which 76 on 139 pSS patients had an examination by a dermatologist) and baseline data of the TEARS randomized trial (110 patients with recent or active pSS treated with rituximab or placebo and evaluated for skin dryness using a visual analogue scale (VAS) out of 100).Skin manifestations included in the EULAR Sjögren syndrome disease activity index (ESSDAI) were rare in the ASSESS cohort (n=16/395, 4.1%, mainly purpuras; only 3 had high activity), but they were associated with activity in the other ESSDAI domains (peripheral neurological (P0.001), muscular (P0.01), haematological (P0.05), biological (P0.05), history of arthritis (P0.01), splenomegaly (P0.05) and higher gamma globulin levels (P0.01)). In the diapSS cohort, compared to pSS patients not receiving a dermatological consultation, the pSS patients who had a dermatological consultation had significantly more dermatological involvement outside the ESSDAI score [38.2% (29/76) versus 15.9% (10/63); P0.01]. The TEARS study showed a high prevalence of cutaneous dryness (VAS50; 48.2%) and found that patients with dry skin had higher VAS pain (P0.01) and drought (P0.01) scores.ESSDAI skin activity is rare and associated with hypergammaglobulinemia and ESSDAI activity. Systematic dermatological examination is informative for non-specific lesions. The most common skin disorder is skin dryness, which is associated with a higher pain and overall subjective dryness.
Published: 2020
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35. Long-term outcomes in patients with PET-predicted poor-responsive HER2-positive breast cancer treated with neoadjuvant bevacizumab added to trastuzumab and docetaxel: 5-year follow-up of the randomised Avataxher study

Author: Jean-Yves Pierga, Alina Berriolo-Riedinger, Thierry Petit, Laurent Arnould, David Coeffic, Abdennour Ferhat, Gilles Paintaud, Jean-Briac Prevost, Pierre-Francois Dupre, Fanny Le Du, Thomas Bachelot, Marie-Pierre Chauvet, Jean-Marc Ferrero, Gilles Thibault, Kaldoun Kerrou, Philippe Gabelle, Catherine Barbe, Julien Dupin, Bruno Coudert, Marie-Ange Mouret-Reynier, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Institut Curie [Paris], Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Paul Strauss, CRLCC Paul Strauss, Centre Eugène Marquis (CRLCC), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Centre Léon Bérard [Lyon], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Roche France, Département d'information médicale [Centre Georges-François Leclerc] (DIM), UNICANCER-UNICANCER, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université de Lille-UNICANCER
Subjects: Oncology, medicine.medical_specialty, Positron emission tomography, Early pet assessment, Bevacizumab, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 01 natural sciences, Group B, 03 medical and health sciences, Her-2 positive breast cancer, 0302 clinical medicine, Breast cancer, Trastuzumab, Internal medicine, medicine, Adjuvant therapy, 030212 general & internal medicine, 0101 mathematics, Adverse effect, Long-term follow-up, Neoadjuvant therapy, lcsh:R5-920, business.industry, 010102 general mathematics, General Medicine, medicine.disease, 3. Good health, Docetaxel, pathological complete response, Δsuvmax, Neoadjuvant, lcsh:Medicine (General), business, Research Paper, medicine.drug
Abstract: Background: The open-label, randomised Phase 2 AVATAXHER study (NCT01142778) demonstrated that early PET assessment identified HER2-positive breast cancer patients who responded poorly to neoadjuvant docetaxel plus trastuzumab. Adding neoadjuvant bevacizumab for PET-predicted poor-responders improved pathological complete response (pCR) rates (43.8% vs 24.0%). We investigated long-term study outcomes. Methods: Patients were treated in three groups. All patients initially received two cycles of standard neoadjuvant therapy with [¹⁸F]-FDG PET conducted before each cycle. Those with ≥70% change in the maximum standardised uptake value (∆SUVmax) received four further cycles of standard neoadjuvant therapy (PET responders). PET-predicted poor-responders (∆SUVmax
Published: 2020
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36. The French National Cochlear Implant Registry (EPIIC): Cochlear explantation and reimplantation

Author: Isabelle Mosnier, Stéphane Roman, A. Bozorg-Grayeli, Y. Lerosey, Valérie Franco-Vidal, K. Mezouaghi, R. Marianowski, P. Piller, N. Klopp, C. Vincent, Alexandre Karkas, Natalie Loundon, Nicolas Guevara, T. Mom, Olivier Deguine, K. Aubry, Emmanuel Lescanne, S. Roux-Vaillard, Benoit Godey, L. Tavernier, C. Eyermann, Cécile Parietti-Winkler, R Hermann, F. Merklen, M. Labrousse, Sébastien Schmerber, Eric Truy, S. Moreau, J.-P. Lebreton, N. Noël-Petroff, E. Radafy, A. Coudert, C. Poncet, Philippe Bordure, Equipe IFTIM [ImViA - EA7535], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Imagerie et Vision Artificielle [Dijon] (ImViA), Université de Bourgogne (UB)-Université de Bourgogne (UB), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille, Inserm, CHU Lille, Hôpital Edouard Herriot [CHU - HCL], Service d'Oto-rhino-laryngologie (ORL) et chirurgie cervico-faciale [CHU Limoges], Centre hospitalier universitaire de Nantes [CHU Nantes], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand [CHU Dijon], Centre Hospitalier Universitaire de Toulouse [CHU Toulouse], CHU Strasbourg, CHU Bordeaux [Bordeaux], CHU Pontchaillou [Rennes], Hôpital Pasteur [Nice] [CHU], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] [CHU ST-E], CHU Amiens-Picardie, Centre Hospitalier Universitaire de Reims [CHU Reims], Centre hospitalier universitaire de Poitiers [CHU Poitiers], CHU Rouen, CHU Trousseau [Tours], CHU Necker - Enfants Malades [AP-HP], Hôpital Morvan - CHRU de Brest [CHU - BREST ], Service ORL [Hôpital Gui de Chauliac] [CHRU de Montpellier], Centre Hospitalier Universitaire de La Réunion [CHU La Réunion], CHU Gabriel Montpied [Clermont-Ferrand], CHU Caen, CHU Pitié-Salpêtrière [AP-HP], Hôpital Robert Debré Paris, Hôpital Le Lamentin Bourg [CHU de la Martinique], CHU Marseille, Centre Hospitalier Universitaire d'Angers [CHU Angers], CHU Grenoble, Centre Hospitalier Régional Universitaire de Besançon [CHRU Besançon], and Médicaments et biomatériaux à libération contrôlée: mécanismes et optimisation - Advanced Drug Delivery Systems - U 1008 [MBLC - ADDS]
Subjects: Adult, Reoperation, medicine.medical_specialty, Time Factors, Adolescent, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Young Adult, 03 medical and health sciences, 0302 clinical medicine, Cochlear implant, medicine, Humans, Prospective Studies, Registries, Child, 030223 otorhinolaryngology, Cochlear implantation, Prospective cohort study, Device Removal, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, business.industry, Age Factors, Infant, Registry, Reimplantation, Explantation, Middle Aged, Cochlear Implantation, Prosthesis Failure, 3. Good health, Surgery, Cochlear Implants, Otorhinolaryngology, Child, Preschool, Replantation, 030220 oncology & carcinogenesis, France, Implant, business, Pediatric population
Abstract: This study aims to determine the frequency and causes of cochlear explants with re-implantation (ERI) after 5 years’ follow up of the patients included in the French national EPIIC (étude post-inscription des implants cochléaires) registry tracking patients with cochlear implantation. This multicenter, descriptive prospective study was conducted on 5051 patients enrolled in the EPIIC database between January 2012 and December 2016. Ninety-five patients (1.9%) received a primary implant and an ERI during the study. Of these, four benefitted from two ERIs. The number of ERIs was significantly higher in the pediatric population than among adults. The explantation and reimplantation were performed simultaneously in 86% of cases. The reasons for explantation were: in 46.4% of cases linked to a malfunction of the implant, and in 39.3% of cases for medical or surgical reasons. The number of electrodes inserted was significantly higher after the ERI than after the first implantation. There was just one post-ERI infection for these 95 explanted and re-implanted patients. As well as explantation with reimplantation rarely being necessary, it generally presents no major surgical difficulty and in most cases it allows a better integration than in the first implantation. 137;Supplement 1
Published: 2020
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37. Burn out, le mode d’exercice en question

Author: Robin, Noluenn, Josso, Nolwenn, Launay, Titouan, Pougnet, Laurence, Robin Paulard, Isabelle, Pougnet, Richard, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Hôpital d'Instruction des Armées Clermont Tonnerre, Service de Santé des Armées, Laboratoire d'Études et de Recherche en Sociologie (LABERS), Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Brestois des Sciences de l'Homme et de la Société (IBSHS), Université de Brest (UBO), and Hôpital Morvan - CHRU de Brest (CHU - BREST )
Subjects: burn out, sage-femme, santé au travail, syndrome d’épuisement professionnel, [SDV]Life Sciences [q-bio], épidémiologie
Abstract: International audience; Les sages-femmes sont soumises à de nombreuses contraintes, qui peuvent varier selon le mode d’exercice. Une étude a été réalisée auprès des professionnels exerçant dans une région française, afin d’évaluer la prévalence du syndrome d’épuisement professionnel et ses facteurs de risque. Les sages-femmes qui travaillent à l’hôpital semblent être les plus touchées par le burn out.
Published: 2020
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38. Factors associated with poor fetal outcome in placental abruption

Author: C. Tremouilhac, Philippe Merviel, Juliette Chauvet, Charles Bellot, Karine Lacut, Emmanuelle Le Moigne, Annabelle Remoué, Pascale Marcorelles, Claire de Moreuil, Brigitte Pan Petesch, Jacob Hannigsberg, Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Laboratoire sur les interactions Epithéliums Neurones (LIEN), Université de Brest (UBO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Centre Hospitalier Intercommunal de Cornouaille [Quimper] (CHI Cornouaille [Quimper]), and CCSD, Accord Elsevier
Subjects: Adult, Male, medicine.medical_specialty, pre-eclampsia, [SDV]Life Sciences [q-bio], Placenta, Intrauterine growth restriction, chorioamniotitis, 030204 cardiovascular system & hematology, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Risk Factors, abruption, Internal Medicine, medicine, Humans, Abruptio Placentae, Retrospective Studies, Aspirin, Fetus, 030219 obstetrics & reproductive medicine, Placental abruption, business.industry, Obstetrics, Infant, Newborn, Pregnancy Outcome, Obstetrics and Gynecology, medicine.disease, Pathophysiology, 3. Good health, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, medicine.anatomical_structure, inflammation, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, Gestation, stillbirth, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, France, business, medicine.drug
Abstract: International audience; Objectives: We aimed at describing placental abruption in our county and at evaluating factors associated with poor fetal outcome.Study design: In this case-control study, women with placental abruption were identified from two databases of Brest University Hospital between January 2013 and December 2018.Main outcome measures: Placental histological findings, course of pregnancies, maternal and fetal characteristics were described and compared between cases (placental abruption with stillbirth or neonatal death) and controls.Results: We identified 135 placental abruption, of whom 24.4% were complicated with stillbirth and 6.5% with neonatal death. Forty percent of women were smokers and 14.1% had a history of vasculoplacental disorder. Pregnancies were complicated with 42.2% of pre-eclampsia and 43% of intrauterine growth restriction. Cases were associated with more autoimmune diseases in mother (20.0% versus 3.2%, P = 0.003), more aspirin or heparin use during pregnancy (20.0% versus 6.3%, P = 0.03), less pre-eclampsia (25.0% versus 49.5%, P = 0.01) and more deliveries ≤ 34 weeks of gestation (80.0% versus 43.2%, P = 0.0001) than controls. Placentas from cases showed more placental indentation ≥ 30% (42.5% versus 5.3%, P < 0.0001) and less histological chronic inflammation, especially less chronic chorioamniotitis (2.5% versus 24.2%, P = 0.002) than controls. In multivariate analysis, factors negatively associated with poor fetal outcome were placental histological chronic inflammation (P = 0.01) and macroscopic infarcts (P = 0.01).Conclusions: Poor fetal outcome is negatively associated with certain placental histological chronic lesions, but not with pre-eclampsia, what suggests various pathophysiological processes among placental abruption.
Published: 2020
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39. Wearing of face masks by healthcare workers during covid-19 lockdown: what did the public observe through the French media?

Author: Raoul Baron, Jérémy Picard, G. Cornec, Philippe Saliou, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), EFS, and CCSD, Accord Elsevier
Subjects: Microbiology (medical), Adult, Male, Coronavirus disease 2019 (COVID-19), [SDV]Life Sciences [q-bio], Health Personnel, Population, Pneumonia, Viral, Face (sociological concept), COVID-19 pandemic, 030501 epidemiology, Article, 03 medical and health sciences, Betacoronavirus, 0302 clinical medicine, surgical mask, Pandemic, Health care, Medicine, Humans, 030212 general & internal medicine, education, Personal protective equipment, Pandemics, Personal Protective Equipment, education.field_of_study, business.industry, SARS-CoV-2, media, Masks, COVID-19, General Medicine, Public relations, Middle Aged, 3. Good health, Face masks, [SDV] Life Sciences [q-bio], Surgical mask, Infectious Diseases, filtering face piece (FFP) mask, Female, France, 0305 other medical science, business, Coronavirus Infections, Social Media
Abstract: International audience; Wearing a face mask is a major issue in the fight against the spread of the COVID-19 pandemic. The French general population widely started to wear this personal protective equipment usually dedicated to healthcare workers, without being educated to its correct use. People base their behaviour on what they see in the media. However, we observed that mask wearing of healthcare workers published in the media during the pandemic only conformed to good practice guidelines in 70.8% of the photographs collected on some of the main French information websites. Health authorities should communicate widely regarding the good practices for mask wearing in the general population.
Published: 2020
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40. Amniotic fluid peptides predict postnatal kidney survival in developmental kidney disease

Author: Romain Favre, Marie-Pierre Lavocat, Bernard Boudailliez, Charlotte Lucas, Camille Fédou, Jean-Sebastien Saulnier Blache, Anne-Sophie Weingertner, Blandine Hougas, Joost P. Schanstra, Pascal Gaucherand, Sylvie Cloarec, Julie Batut, Catherine Noel, J. Gondry, Philippe Eckart, Norbert Winer, Benjamin Breuil, Gérard Champion, Jean-Baptiste Benevent, Franck Perrotin, Christophe Vayssière, Florence Biquard, Harald Mischak, Gwenaelle Le Bouar, Jérôme Massardier, Françoise Conte Auriol, Pedro Magalhães, Sophie Martin, Jean-Paul Bory, Sophie Collardeau-Frachon, Eve Mousty, Lucie Bessenay, Corinne Floch, Julie Klein, Amelie Ryckewaert, Elisabeth Simon, Alain Martin, Guylène Bourdat-Michel, Marie-Françoise Froute, Franz Schaefer, Pascale Marcorelles, Stéphane Decramer, Nabila Moussaoui, Franck Boizard, Marie-Christine Manca-Pellissier, Mariannick Maupin-Hyvonnet, Marion Groussolles, Jean-Marie Delbosc, Guylène Feuillet, Anke Raaijmakers, François Nobili, Sophie Taque, Petra Zürbig, Vincent Guigonis, Audrey Casemayou, Patrick Blader, An Hindryckx, Luc Decatte, Karel Allegaert, Ophélie Lescat, Eric Neau, Odile Basmaison, Emma Allain-Launay, Agnes Sartor, Jean-Loup Bascands, Claudine Le Vaillant, Hélène Laurichesse Delmas, Bénédicte Buffin-Meyer, Nadia Lounis, Anne-Hélène Saliou, Véronique Baudouin, Elena Levtchenko, Maryse Fiorenza, Christine Pietrement, Valérie Goua, Marina Merveille, Laurent Bidat, Yves Aubard, Alexandra Benachi, Sylvie Kessler, Loic De Parscau, Jean-François Oury, Fabienne Prieur, Centre de biologie du développement (CBD), Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Equipe 7 Inserm U1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées, University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Laboratoire de Gérontechnologie [Hôpital La Grave-CHU de Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Gérontopôle, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Gatien de Clocheville [Tours] (CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Clermont-Ferrand, Centre hospitalier universitaire de Nantes (CHU Nantes), Groupe de Recherche sur l'Analyse Multimodale de la Fonction Cérébrale - UMR INSERM_S 1105 (GRAMFC), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Centre Hospitalier René Dubos [Pontoise], Hôpital Louis Mourier - AP-HP [Colombes], Centre Hospitalier Universitaire [Grenoble] (CHU), Les Hôpitaux Universitaires de Strasbourg (HUS), AP-HP Hôpital universitaire Robert-Debré [Paris], Centre Hospitalier Universitaire de Reims (CHU Reims), Hospices Civils de Lyon (HCL), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Centre de dépistage des Carmes [Toulouse] (CDC), Hôpital des Enfants, CHU Toulouse [Toulouse], Laboratoire sur les interactions Epithéliums Neurones (LIEN), Université de Brest (UBO), Département de Pathologie [CHU Lyon-Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Mosaiques Diagnostics & Therapeutics AG [Hannover, Germany], University of Glasgow, Hannover Medical School [Hannover] (MHH), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI), Diabète athérothrombose et thérapies Réunion Océan Indien (DéTROI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), Heidelberg University, Centre De Référence des Maladies Rénales Rares du Sud Ouest (SORARE), Centre De Référence des Maladies Rénales Rares du Sud Ouest, BIOMAN consortium: Karel Allegaert, Yves Aubard, Odile Basmaison, Jean-Baptiste Benevent, Florence Biquard, Gérard Champion, Jean-Marie Delbosc, Philippe Eckart, Marie-Françoise Froute, Pascal Gaucherand, Marion Groussolles, Vincent Guigonis, Blandine Hougas, Gwenaelle Le Bouar, Alain Martin, Sophie Martin, Mariannick Maupin-Hyvonnet, Marina Merveille, Eve Mousty, François Nobili, Amelie Ryckewaert, Agnes Sartor, Sophie Taque, Norbert Winer, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Development and Regeneration, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Gérontopôle-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse], Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clocheville, Department of Pediatric and Prenatal Radiology, Timone's Children-Hospital (APHM), Hôpital Dupuytren [CHU Limoges], CHU Toulouse, Hôpital des Enfants, Unité de Gastroentérologie, Hépatologie et Nutrition, Département de Pédiatrie, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Groupement Hospitalier Est [Bron], University Medical Center Heidelberg, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Saulnier-Blache, Jean Sébastien, Pôle Gériatrie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), and Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Pathology, medicine.medical_specialty, Amniotic fluid, Urinary system, [SDV]Life Sciences [q-bio], congenital anomalies of the kidney and the urinary tract, 030232 urology & nephrology, Kidney, Fetal Kidney, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, medicine, Animals, Humans, termination of pregnancy, Prospective Studies, Child, Urinary Tract, Zebrafish, ComputingMilieux_MISCELLANEOUS, Fetus, business.industry, infants, Area under the curve, amniotic fluid, prediction, medicine.disease, 3. Good health, Pronephros, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, Nephrology, Urogenital Abnormalities, peptides, Female, Kidney Diseases, business, management, Kidney disease
Abstract: Although a rare disease, bilateral congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of end stage kidney disease in children. Ultrasound-based prenatal prediction of postnatal kidney survival in CAKUT pregnancies is far from accurate. To improve prediction, we conducted a prospective multicenter peptidome analysis of amniotic fluid spanning 140 evaluable fetuses with CAKUT. We identified a signature of 98 endogenous amniotic fluid peptides, mainly composed of fragments from extracellular matrix proteins and from the actin binding protein thymosin-β4. The peptide signature predicted postnatal kidney outcome with an area under the curve of 0.96 in the holdout validation set of patients with CAKUT with definite endpoint data. Additionally, this peptide signature was validated in a geographically independent sub-cohort of 12 patients (area under the curve 1.00) and displayed high specificity in non-CAKUT pregnancies (82 and 94% in 22 healthy fetuses and in 47 fetuses with congenital cytomegalovirus infection respectively). Change in amniotic fluid thymosin-β4 abundance was confirmed with ELISA. Knockout of thymosin-β4 in zebrafish altered proximal and distal tubule pronephros growth suggesting a possible role of thymosin β4 in fetal kidney development. Thus, recognition of the 98-peptide signature in amniotic fluid during diagnostic workup of prenatally detected fetuses with CAKUT can provide a long-sought evidence base for accurate management of the CAKUT disorder that is currently unavailable. ispartof: KIDNEY INTERNATIONAL vol:99 issue:3 pages:737-749 ispartof: location:United States status: published
Published: 2020
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41. Calibration of pathogenicity due to variant-induced leaky splicing defects by using BRCA2 exon 3 as a model system

Author: Gaia Castelain, Capucine Delnatte, Pascaline Gaildrat, Myriam Vezain, Laëtitia Meulemans, Nadia Boutry-Kryza, Teresa Sullivan, Dominique Stoppa-Lyonnet, Julie Hauchard, Pascal Pujol, Thierry Frebourg, Séverine Audebert-Bellanger, Daniela Di Giacomo, Danièle Muller, Aurélie Drouet, Hélène Tubeuf, Susan W. Reid, Julie Rondeaux, Mélanie Léoné, Violaine Bourdon, Françoise Bonnet-Dorion, Françoise Révillion, Hélène Larbre, Shyam K. Sharan, Omar Soukarieh, Sandrine M. Caputo, Alice Fiévet, Laurence Venat-Bouvet, Virginie Caux-Moncoutier, Alexandra Martins, Fátima Vaz, Angela R. Solano, Claude Houdayer, Eileen Southon, Chrystelle Colas, Marine Guillaud-Bataille, Linda Cleveland, Sophie Krieger, 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 recherche de l'Institut Curie [Paris], Institut Curie [Paris], Université Paris sciences et lettres (PSL), National Cancer Institute Frederick, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Département de biologie et pathologie médicales [Gustave Roussy], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Nantes (CHU Nantes), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Jean Godinot [Reims], UNICANCER, Centre Paul Strauss, CRLCC Paul Strauss, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Hôpital Dupuytren [CHU Limoges], Centro de Educación Médica e Investigaciones Clínicas (CEMIC), and This work was funded by a translational research grant from the French National Cancer Institute and the Direction Générale de l’Offre des Soins (INCa/DGOS, AAP/CFB/CI), by the OpenHealth Institute, the Groupement des Entreprises Fran¸caises dans la Lutte contre le Cancer (Gefluc), the Fédération Hospitalo-Universitaire (FHU) Normandy Centre for Genomic and Personalized Medicine (NGP), the European Union and Region Normandie as well as by the Intramural Research Program from the Center for Cancer Research of the NCI, NIH. Europe gets involved in Normandie with European Regional Development Fund (ERDF). H. Tubeuf was funded by a CIFRE PhD fellowship (#2015/0335) from the French Association Nationale de la Recherche et de la Technologie (ANRT) in the context of a public–private partnership between INSERM and Interactive Biosoftware and by two short-term fellowship from EMBO (#3436) and Cancéropôle Nord-Ouest. J. Hauchard and G. Castelain were sponsored by the French INCa.
Subjects: 0301 basic medicine, Cancer Research, endocrine system diseases, In silico, Genes, BRCA2, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Biology, MESH: Protein Isoforms, Article, 03 medical and health sciences, Exon, Mice, 0302 clinical medicine, Protein-fragment complementation assay, Animals, Humans, Protein Isoforms, MESH: Animals, Genetic Predisposition to Disease, skin and connective tissue diseases, Gene, MESH: Mice, Genetics, Ovarian Neoplasms, MESH: Humans, MESH: Alternative Splicing, MESH: Genetic Predisposition to Disease, RNA, Exons, MESH: Ovarian Neoplasms, Alternative Splicing, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, RNA splicing, Female, Haploinsufficiency, MESH: Exons, MESH: Female, MESH: Breast Neoplasms, MESH: Genes, BRCA2, Minigene
Abstract: BRCA2 is a clinically actionable gene implicated in breast and ovarian cancer predisposition that has become a high priority target for improving the classification of variants of unknown significance (VUS). Among all BRCA2 VUS, those causing partial/leaky splicing defects are the most challenging to classify because the minimal level of full-length (FL) transcripts required for normal function remains to be established. Here, we explored BRCA2 exon 3 (BRCA2e3) as a model for calibrating variant-induced spliceogenicity and estimating thresholds for BRCA2 haploinsufficiency. In silico predictions, minigene splicing assays, patients' RNA analyses, a mouse embryonic stem cell (mESC) complementation assay and retrieval of patient-related information were combined to determine the minimal requirement of FL BRCA2 transcripts. Of 100 BRCA2e3 variants tested in the minigene assay, 64 were found to be spliceogenic, causing mild to severe RNA defects. Splicing defects were also confirmed in patients' RNA when available. Analysis of a neutral leaky variant (c.231T>G) showed that a reduction of approximately 60% of FL BRCA2 transcripts from a mutant allele does not cause any increase in cancer risk. Moreover, data obtained from mESCs suggest that variants causing a decline in FL BRCA2 with approximately 30% of wild-type are not pathogenic, given that mESCs are fully viable and resistant to DNA-damaging agents in those conditions. In contrast, mESCs producing lower relative amounts of FL BRCA2 exhibited either null or hypomorphic phenotypes. Overall, our findings are likely to have broader implications on the interpretation of BRCA2 variants affecting the splicing pattern of other essential exons. Significance: These findings demonstrate that BRCA2 tumor suppressor function tolerates substantial reduction in full-length transcripts, helping to determine the pathogenicity of BRCA2 leaky splicing variants, some of which may not increase cancer risk.
Published: 2020
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42. What is the best hip center location method to compute HKA angle in computer-assisted orthopedic surgery? In silico and in vitro comparison of four methods

Author: Christian Lefèvre, N. Poirier, Z Dib, Hoel Letissier, Guillaume Dardenne, Eric Stindel, Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), and Hôpital Morvan - CHRU de Brest (CHU - BREST )
Subjects: Accuracy and precision, medicine.medical_specialty, Knee Joint, [SDV]Life Sciences [q-bio], Arthroplasty, Replacement, Hip, In silico, Computer-assisted orthopedic surgery, 03 medical and health sciences, 0302 clinical medicine, Cadaver, medicine, Image noise, Humans, In vitro study, Orthopedics and Sports Medicine, Prospective Studies, Instant centre of rotation, 030222 orthopedics, business.industry, 030229 sport sciences, Surgery, Surgery, Computer-Assisted, Hip Joint, Nuclear medicine, business, Ankle Joint
Abstract: In computer-assisted orthopedic surgery, the hip center (HC) can be determined by calculating the center of rotation of the femur in relation to the pelvis. Several methods are available: Gamage, Halvorsen, Pivot or Least-Moving Point (LMP). To our knowledge, no studies have compared these four methods. We therefore conducted in silico and in vitro experiments to assess whether their accuracy and precision in locating the HC and calculating the hip-knee-ankle (HKA) angle were equivalent.The four methods show similar accuracy and precision.The in silico experiment assessed the independent influence of four parameters (camera noise, acetabular noise, movement amplitude, and number of circumductions) on accuracy. The accuracy and precision of the four methods and the impact on HKA ankle calculation were assessed in an in vitro study on six cadaver limbs.In the in silico experiment, all differences according to method were significant (p0.0002). The Pivot method was the most accurate for acetabular and camera noise, number of circumductions, and movement amplitude. With the LMP, Pivot, Gamage and Halvorsen methods, error was respectively 23.07±8.40 (range 2.10-54.67) mm, 1.98±081 (0.15-4.89) mm, 28.18±3.42 (18.57-37.60) mm and 2.84±1.46 (0.11-9.44) mm depending on camera noise, 1.65±0.72 (0.13-4.80) mm, 0.52±0.22 (0.05-1.23) mm, 3.02±0.57 (0.60-4.78) mm and 0.61±0.27 (0.04-1.82) mm depending on movement amplitude, 0.50±0.20 (0.05-1.34) mm, 0.18±0.08 (0.01-0.44) mm, 0.36±0.14 (0.03-0.80) mm and 0.21±0.09 (0.01-0.55) mm depending on number of circumductions, and 11.30±5.77 (0.56-37.87) mm, 2.78±1.47 (0.10-8.77) mm, 88.08±8.85 (60.59-117.79) mm and 24.33±9.82 (1.40-66.17) mm depending on acetabular noise. In the in vitro experiment, differences were non-significant between the Pivot and LMP methods (p0.98) and between the Gamage and Halvorsen methods (p0.65). With the LMP, Pivot, Gamage and Halvorsen methods, precision was respectively 8.2±4.6 (3.3-23.6) mm, 7.3±3.6 (3.4-14.1) mm, 33.6±19.1 (4.7-111.4) mm and 35.0±25.0 (4.7-132.5) mm. Accuracy was 13.5±8.2 (3.2-40.7) mm. 12.3±6.4 (3.2-23.6) mm, 47.0±33.3 (6.2-176.6) mm and 40.3±27.8 (6.1-130.3) mm. The LMP and Pivot methods were thus more accurate and more precise than the Gamage and Halvorsen methods. HKA angle error was 1.1±0.9° (0.1-3.7) and 0.9±0.8° (0.0-2.5) with the LMP and Pivot methods, and 3.2±2.7° (0.0-12.7) and 3.8±3.5° (0.0-13.3) with the Gamage and Halvorsen methods.The study highlighted differences between the four methods of HC location in computer-assisted surgery; the Pivot method was the most accurate and precise, thus falsifying the study hypothesis.III, prospective comparative in silico and in vitro study.
Published: 2019
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43. Psychosocial Impact of Predictive Genetic Testing in Hereditary Heart Diseases: The PREDICT Study

Author: Elise Schaefer, Delphine Dupin Deguine, C. Rouzier, Estelle Gandjbakhch, Krystelle Séné, Claire Cécile Michon, Marie Lise Babonneau, Philippe Charron, Caroline Sawka, Bertrand Isidor, Jean François Pruny, Mélanie Hebert, Stéphanie Staraci, Isabelle Denjoy, Caroline Rooryck-Thambo, Ibticem Raji, Rafik Mansouri, Aurélien Palmyre, Linda Akloul, Sandrine Brice, Annick Toutain, Sophie Tezenas du Montcel, Angelique Curjol, Carole Maupain, Gipsy Billy, Céline Bordet, Alexandre Moerman, Pascale Richard, Marcela Gargiulo, Véronique Fressart, Elsa Le Boette, Flavie Ader, Bruno Leheup, Marc Planes, Karine Nguyen, A.C. Brehin, Jean Michael Mazzella, Amine Bekhechi, Service de Génétique Cytogénétique et Embryologie [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), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Cardiologie [CHU Pitié-Salpêtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), 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), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Ambroise Paré [AP-HP], Service de Génétique Médicale [Lille], Institut de génétique médicale-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, CHU Pontchaillou [Rennes], 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), Normandie Université (NU), CHU Rouen, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Bordeaux [Bordeaux], CHU Strasbourg, Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Pointe-à-Pitre/Abymes [Guadeloupe], CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Morvan - CHRU de Brest (CHU - BREST ), 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 de Saint-Brieuc, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité Fonctionnelle de Cardiogénétique et Myogénétique Moléculaire et Cellulaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Université de Paris - UFR Pharmacie [Santé] (UP UFR Pharmacie), Université de Paris (UP), Sorbonne Université (SU), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut National de la Santé et de la Recherche Médicale (INSERM)-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), 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], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Nice Sophia Antipolis (1965 - 2019) (UNS), UFR Pharmacie [Santé] - Université Paris Cité (UFR Pharmacie UPCité), and Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, cardiomyopathies, medicine.medical_specialty, lcsh:Medicine, 030204 cardiovascular system & hematology, 030105 genetics & heredity, Article, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, History of depression, Medicine, Prospective cohort study, predictive genetic testing, Genetic testing, hereditary heart diseases, medicine.diagnostic_test, business.industry, lcsh:R, distress, Retrospective cohort study, social, General Medicine, anxiety, Family life, 3. Good health, Distress, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Anxiety, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, psychological, medicine.symptom, business, Psychosocial
Abstract: Predictive genetic testing (PGT) is offered to asymptomatic relatives at risk of hereditary heart disease, but the impact of result disclosure has been little studied. We evaluated the psychosocial impacts of PGT in hereditary heart disease, using self-report questionnaires (including the State-Trait Anxiety Inventory) in 517 adults, administered three times to the prospective cohort (PCo: n = 264) and once to the retrospective cohort (RCo: n = 253). The main motivations for undergoing PGT were &ldquo, to remove doubt&rdquo, and &ldquo, for their children&rdquo, The level of anxiety increased between pre-test and result appointments (p &lt, 0.0001), returned to baseline after the result (PCo), and was moderately elevated at 4.4 years (RCo). Subjects with a history of depression or with high baseline anxiety were more likely to develop anxiety after PGT result (p = 0.004 and p &lt, 0.0001, respectively), whatever it was. Unfavourable changes in professional and/or family life were observed in 12.4% (PCo) and 18.7% (RCo) of subjects. Few regrets about PGT were expressed (0.8% RCo, 2.3% PCo). Medical benefit was not the main motivation, which emphasises the role of pre/post-test counselling. When PGT was performed by expert teams, the negative impact was modest, but careful management is required in specific categories of subjects, whatever the genetic test result.
Published: 2020
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44. Vécu au travail des sages-femmes, une analyse textuelle

Author: Robin, Noluenn, Josso, Nolwenn, Launay, Titouan, Robin Paulard, Isabelle, Pougnet, Laurence, Pougnet, Richard, Laboratoire de Biologie structurale, Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Études et de Recherche en Sociologie (LABERS), Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Brestois des Sciences de l'Homme et de la Société (IBSHS), Université de Brest (UBO), and Hôpital Morvan - CHRU de Brest (CHU - BREST )
Subjects: [SDV]Life Sciences [q-bio]
Published: 2020
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45. L’allaitement est-il un 'bien' ?

Author: Pougnet, Richard, Tanneau, Coralie, Pougnet, Laurence, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Laboratoire d'Études et de Recherche en Sociologie (LABERS), Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Brestois des Sciences de l'Homme et de la Société (IBSHS), Université de Brest (UBO), Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), and Université d'Angers (UA)
Subjects: [SDV]Life Sciences [q-bio]
Published: 2020
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46. Myosites infectieuses

Author: B. Molina, A. Pogossian, C. De Moreuil, B. Rouvière, R. Le Berre, Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Inserm UMR 1227 Immunothérapies et Pathologies Lymphocytaires B, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), and CCSD, Accord Elsevier
Subjects: [SDV] Life Sciences [q-bio], 0303 health sciences, 03 medical and health sciences, 0302 clinical medicine, 030306 microbiology, [SDV]Life Sciences [q-bio], Gastroenterology, Internal Medicine, 030212 general & internal medicine
Published: 2020
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47. First‐line pembrolizumab for non–small cell lung cancer patients with PD‐L1 ≥50% in a multicenter real‐life cohort: The PEMBREIZH study

Author: Karim Amrane, Gilles Robinet, Ronan Abgral, Gilles Quere, Jean-Louis Bizec, Éric Goarant, Sylvie Gouva, Cyril Bernier, Renaud Descourt, R. Lamy, Hervé Lena, Guillaume Léveiller, Florence Gadby, Ulrike Schick, Margaux Geier, Romain Corre, Christos Chouaid, CHRU Brest, F-29200 Brest, France, Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Centre Hospitalier Intercommunal de Cornouaille [Quimper] (CHI Cornouaille [Quimper]), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Yves le Foll, CH des Pays Morlaix, CH Bretagne Sud, CH Bretagne Atlantique, CH de Saint-Malo, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHRU Brest - Service de médecine nucléaire (CHU - BREST - Med Nucléaire), Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre hospitalier Rene Pleven de Dinan, Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Service de Pneumologie [CHI Créteil], CHI Créteil, IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), and 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)
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, Longitudinal study, Lung Neoplasms, Pembrolizumab, B7-H1 Antigen, Antineoplastic Agents, Immunological, 0302 clinical medicine, non–small cell lung cancer, Carcinoma, Non-Small-Cell Lung, PD‐L1 tumor proportion score, Longitudinal Studies, Original Research, Aged, 80 and over, biology, Real world, Middle Aged, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Survival Rate, 030220 oncology & carcinogenesis, Cohort, Female, pembrolizumab, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antibodies, Monoclonal, Humanized, lcsh:RC254-282, PD-L1 tumor proportion score, 03 medical and health sciences, PD-L1, Internal medicine, medicine, Humans, first‐line monotherapy, Radiology, Nuclear Medicine and imaging, Lung cancer, Adverse effect, non-small cell lung cancer, Aged, Retrospective Studies, Performance status, business.industry, Clinical Cancer Research, medicine.disease, Clinical trial, 030104 developmental biology, biology.protein, first-line monotherapy, business, Follow-Up Studies
Abstract: Background The KEYNOTE‐024 trial demonstrated that pembrolizumab, a PD‐1 inhibitor, significantly improves progression‐free survival (PFS) and overall survival (OS) in selected patients with previously untreated advanced non–small cell lung cancer (NSCLC) with a PD‐L1 tumor proportion score (TPS) ≥50% and without EGFR/ALK aberrations. The main aim of this study was to report the efficacy and safety profile of pembrolizumab in real‐life conditions. Method This was a French retrospective multicenter longitudinal study of 108 consecutive patients with advanced NSCLC, a PD‐L1 TPS ≥50% and without EGFR/ALK aberrations who were treated by pembrolizumab, in first line. Patient data were obtained from medical files. Results The main characteristics of the cohort were: median age [range] 66.7 [37‐87] years, 64.8% male, 23.1% with a performance status (PS) of 2, and 88.9% current or former smokers. Eighty‐seven percent had stage IV NSCLC at diagnosis, 9.2% untreated brain metastases at inclusion,. With a median follow‐up of 8.2 months, the median PFS was 10.1 months (95% CI, 8.8‐11.4). The objective response rate was 57.3% (complete response 2.7%, partial response 54.6%). Disease control rate was 71.1%. At 6 months, the OS rate estimated was 86.2%. Treatment‐related adverse events (AE) of grade 3 occurred in 8% of patients. There were no grade 4 or 5 AEs. Conclusion In a real‐life cohort of advanced NSCLC patients (including PS 2 and untreated brain metastases), with PD‐L1 TPS ≥50%, pembrolizumab demonstrates similar PFS to the pivotal clinical trial., This retrospective multicenter longitudinal study was intended to report the efficacy and safety profile of pembrolizumab in real‐life conditions for the first‐line treatment of advanced squamous none small‐cell lung cancer. The median progression free survival was 10.1 months (95% CI, 8.8‐11.4) and the treatment‐related adverse events of grade 3 occurred in 8% of patients. This study demonstrates similar progression‐free survival to KEYNOTE‐024.
Published: 2020
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48. Financial incentives for smoking cessation in pregnancy: multicentre randomised controlled trial

Author: Noémi Berlin, Ivan Berlin, Martine Breton, Léontine Goldzahl, Marie Malecot, Florence Jusot, Service de Pharmacologie 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), EconomiX, Université Paris Nanterre (UPN)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier Saint Joseph - Saint Luc [Lyon], Hôpital Morvan - CHRU de Brest (CHU - BREST ), Laboratoire d'Economie de Dauphine (LEDa), Institut de Recherche pour le Développement (IRD)-Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), EDHEC Business School (EDHEC), Université catholique de Lille (UCL), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], École des hautes études commerciales du Nord (EDHEC), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, medicine.medical_specialty, medicine.medical_treatment, Birth weight, media_common.quotation_subject, Health Behavior, Corrections, 01 natural sciences, law.invention, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Reward, Randomized controlled trial, Pregnancy, law, medicine, Birth Weight, Humans, Single-Blind Method, 030212 general & internal medicine, 0101 mathematics, media_common, Motivation, Obstetrics, business.industry, Research, 010102 general mathematics, Pregnancy Outcome, Obstetrics and Gynecology, Gestational age, Prenatal Care, General Medicine, Odds ratio, Abstinence, medicine.disease, 3. Good health, Smoking cessation, Female, Smoking Cessation, Apgar score, France, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objective To evaluate the efficacy of financial incentives dependent on continuous smoking abstinence on smoking cessation and birth outcomes among pregnant smokers. Design Single blind, randomised controlled trial. Setting Financial Incentive for Smoking Cessation in Pregnancy (FISCP) trial in 18 maternity wards in France. Participants 460 pregnant smokers aged at least 18 years who smoked ≥5 cigarettes/day or ≥3 roll-your-own cigarettes/day and had a pregnancy gestation of Interventions Participants in the financial incentives group received a voucher equivalent to €20 (£17; $23), and further progressively increasing vouchers at each study visit if they remained abstinent. Participants in the control group received no financial incentive for abstinence. All participants received a €20 show-up fee at each of six visits. Main outcome measures The main outcome measure was continuous smoking abstinence from the first post-quit date visit to visit 6, before delivery. Secondary outcomes in the mothers were point prevalence abstinence, time to smoking relapse, withdrawal symptoms, blood pressure, and alcohol and cannabis use in past 30 days. Secondary outcomes in the babies were gestational age at birth, birth characteristics (birth weight, length, head circumference, Apgar score), and a poor neonatal outcome—a composite measure of transfer to the neonatal unit, congenital malformation, convulsions, or perinatal death. Results Mean age was 29 years. In the financial incentives and control groups, respectively, 137 (59%) and 148 (65%) were employed, 163 (71%) and 171 (75%) were in a relationship, and 41 (18%) and 31 (13%) were married. The participants had smoked a median of 60 cigarettes in the past seven days. The continuous abstinence rate was significantly higher in the financial incentives group (16%, 38/231) than control group (7%, 17/229): odds ratio 2.45 (95% confidence interval 1.34 to 4.49), P=0.004). The point prevalence abstinence rate was higher (4.61, 1.41 to 15.01, P=0.011), the median time to relapse was longer (visit 5 (interquartile range 3-6) and visit 4 (3-6), P Conclusions Financial incentives to reward smoking abstinence compared with no financial incentives were associated with an increased abstinence rate in pregnant smokers. Financial incentives dependent on smoking abstinence could be implemented as a safe and effective intervention to help pregnant smokers quit smoking. Trial registration ClinicalTrials.gov NCT02606227 .
Published: 2021
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49. L’apport de l’ACPA dans la prise en charge des hyperclartés nucales

Author: C. Muszynski, G. Jedraszak, Jean Gondry, J. Beal, A.-H. Saliou, Fabrice Sergent, H. Copin, P. Merviel, CHU Amiens-Picardie, Laboratoire de Cytogénétique, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], and Hôpital Morvan - CHRU de Brest (CHU - BREST )
Subjects: Gynecology, Fetus, medicine.medical_specialty, 030219 obstetrics & reproductive medicine, business.industry, [SDV]Life Sciences [q-bio], Obstetrics and Gynecology, Ultrasonic Prenatal Diagnosis, 03 medical and health sciences, 0302 clinical medicine, Reproductive Medicine, Nuchal translucency, Nuchal Translucency Measurement, medicine, 030212 general & internal medicine, business
Abstract: Resume Objectifs Hyperclarte nucale et hygroma colli ont un pronostic neonatal, lorsque le caryotype est normal, qui depend de ce qui sera decouvert lors du suivi medical. L’ACPA a ete systematiquement incorpore a ce suivi par les equipes de diagnostic antenatal. Il n’existe pas de recommandation et peu de donnees dans la litterature sur les avantages a realiser cet examen de facon systematique. L’objectif de notre etude est d’evaluer l’apport de l’ACPA dans ce suivi. Methodes Cinquante et une patientes ont ete incluses sur 18 mois et suivies jusqu’au denouement de leur grossesse aux centres de diagnostic antenatal de Brest et d’Amiens. Le critere d’inclusion etait une hyperclarte nucale > 3,5 mm en echographie du 1er trimestre. Des analyses d’ADN fœtal, par ChromoQuant et ACPA effectuees sur ponction de villosite choriale, et une echographie a 18 SA etaient realisees durant ce suivi. Resultats L’ACPA n’a ete determinante qu’a 2 reprises. L’echographie a 18 SA semble plus sensible dans le depistage d’une anomalie. Lorsque l’ACPA revelait une anomalie, l’echographie permettait d’envisager la presence d’une malformation. Dans 10 cas, l’ACPA n’a pu etre interpretee sur la ponction de villosite choriale. Dans 9 cas, une amniocentese a ete realisee afin d’obtenir ce resultat. Conclusion Au vu des resultats de cette etude l’ACPA est peu souvent determinante ou decisive dans la realisation d’une IMG. Ces elements nous amenent a reflechir a la necessite de maintenir cet examen avant 14SA ou bien de le proposer en seconde intention apres apparition de signes echographiques a 18 SA.
Published: 2020
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50. Immunoglobulin Abnormalities in Gaucher Disease: an Analysis of 278 Patients Included in the French Gaucher Disease Registry

Author: Yann Nguyen, Dries Dobbelaere, Jérôme Stirnemann, Monia Bengherbia, Fabrice Camou, Samia Pichard, Karima Yousfi, Christine Serratrice, Agathe Masseau, Vanessa Leguy-Seguin, Marc G. Berger, Nadia Belmatoug, Dalil Hamroun, Bruno Fantin, Florent Lautredoux, Francis Gaches, Leonardo Astudillo, Anaïs Brassier, Bérengère Cador, Florence Dalbies, Yves-Marie Pers, Thierry Billette de Villemeur, Université de Lille, Hôpital Jeanne de Flandres, 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, Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), CHU Pontchaillou [Rennes], Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Trousseau [APHP], Centre Référence des Maladies Héréditaires du Métabolisme de l'Enfant et de l'Adulte [CHU Necker] (MaMEA Necker), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de réanimation médicale, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Hôpital Morvan - CHRU de Brest (CHU - BREST ), Centre de Référence des Maladies Héréditaires du Métabolisme, Hôpital Jeanne de Flandres-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Joseph Ducuing - Varsovie [Toulouse] (HJD), Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de médecine interne [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Hôpital Robert Debré, Médecine Interne [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Dpt médecine interne [CHU Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Universitaire de Genève, CHU Toulouse [Toulouse], Service de Neuropédiatrie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Hôpital Joseph Ducuing
Subjects: Male, Gaucher disease, monoclonal gammopathy of unknown significance, multiple myeloma, monoclonal gammopathy, polyclonal gammopathy, genetic structures, Paraproteinemias, Gastroenterology, Cohort Studies, lcsh:Chemistry, 0302 clinical medicine, Risk Factors, Multiple myeloma, Medicine, lcsh:QH301-705.5, Spectroscopy, ddc:616, Lymphoma, Non-Hodgkin, Monoclonal gammopathy, Gamma globulin, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, Middle Aged, 3. Good health, Computer Science Applications, 030220 oncology & carcinogenesis, Female, Adult, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Monoclonal gammopathy of unknown significance, Immunoglobulins, Article, Catalysis, Inorganic Chemistry, 03 medical and health sciences, Disease registry, Internal medicine, Humans, Clinical significance, Physical and Theoretical Chemistry, Risk factor, Molecular Biology, Proportional Hazards Models, Retrospective Studies, business.industry, Proportional hazards model, Organic Chemistry, nutritional and metabolic diseases, medicine.disease, eye diseases, Lymphoma, nervous system diseases, lcsh:Biology (General), lcsh:QD1-999, ddc:618.97, Polyclonal gammopathy, gamma-Globulins, business, Glucocerebrosidase, 030215 immunology
Abstract: Gaucher disease (GD) is a rare lysosomal autosomal-recessive disorder due to deficiency of glucocerebrosidase, polyclonal gammopathy (PG) and/or monoclonal gammopathy (MG) can occur in this disease. We aimed to describe these immunoglobulin abnormalities in a large cohort of GD patients and to study the risk factors, clinical significance, and evolution. Data for patients enrolled in the French GD Registry were studied retrospectively. The risk factors of PG and/or MG developing and their association with clinical bone events and severe thrombocytopenia, two markers of GD severity, were assessed with multivariable Cox models and the effect of GD treatment on gammaglobulin levels with linear/logarithmic mixed models. Regression of MG and the occurrence of hematological malignancies were described. The 278 patients included (132 males, 47.5%) were followed up during a mean (SD) of 19 (14) years after GD diagnosis. PG occurred in 112/235 (47.7%) patients at GD diagnosis or during follow-up and MG in 59/187 (31.6%). Multivariable analysis retained age at GD diagnosis as the only independent risk factor for MG (&gt, 30 vs. &le, 30 years, HR 4.71, 95%CI [2.40&ndash, 9.27], p &lt, 0.001). Risk of bone events or severe thrombocytopenia was not significantly associated with PG or MG. During follow-up, non-Hodgkin lymphoma developed in five patients and multiple myeloma in one. MG was observed in almost one third of patients with GD. Immunoglobulin abnormalities were not associated with the disease severity. However, prolonged surveillance of patients with GD is needed because hematologic malignancies may occur.
Published: 2020
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