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1. Cellules de l’allergie : mise au point sur les mastocytes et les éosinophiles

Author: A. Abecassis, J. Vitte, W. Sahli, M. Michel, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)
Subjects: [SDV]Life Sciences [q-bio], Immunology and Allergy
Abstract: International audience
Published: 2022
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2. Safety of Cyproheptadine, an Orexigenic Drug. Analysis of the French National Pharmacovigilance Data-Base and Systematic Review

Author: Valérie Bertrand, Nathalie Massy, Nancy Vegas, Valérie Gras, Christel Chalouhi, Marie-Pierre Tavolacci, Véronique Abadie, Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe Hospitalier du Havre Hôpital Jacques Monod (MONTIVILLIERS) (GHH), CHU Rouen, Normandie Université (NU), Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Maladie Rare Mucoviscidose et Maladies du CFTR (CHU Necker - Enfants Malades [AP-HP]), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Amiens-Picardie, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen]-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), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, and douville, sabine
Subjects: Pediatrics, medicine.medical_specialty, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Cyproheptadine, Hepatic Complication, RJ1-570, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Orexigenic, Pharmacovigilance, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, orexigenic, 030212 general & internal medicine, Adverse effect, Original Research, business.industry, liver failure, cyproheptadine, adverse (side) effects, 3. Good health, cholestase, Clinical trial, Poor Appetite, appetite, Pediatrics, Perinatology and Child Health, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Objectives: Cyproheptadine is a first-generation H1-antihistamine drug first that was distributed in the 1960s. While its orexigenic effect was observed early, cyproheptadine is not yet authorized for this indication in all countries today. There is an increasing medical interest and demand for the orexigenic effect of cyproheptadine, especially in children with poor appetite. As cyproheptadine might be evaluated in future clinical trials, we wanted to assess its safety profile.Methods: Using the French national pharmacovigilance database, we retrospectively analyzed all pediatric and adult reports of adverse effects of cyproheptadine recorded since its first distribution in France. Next, we performed a systematic review of the literature of cyproheptadine adverse effects.Results: Since 1985, 93 adverse effects were reported in the French pharmacovigilance database (adults 81.7%, children 18.3%); these were mainly neurological symptoms (n = 38, adults 71%, children 28.9%), and hepatic complications (n = 15, adults 86.7%, children 13.3%). In the literature, the most frequent adverse effect reported was drowsiness in adults or children, and five case reports noted liver complications in adults. We estimated the frequency of hepatic adverse effects at 0.27 to 1.4/1000, regardless of age.Conclusion: Cyproheptadine can be considered a safe drug. Mild neurological effects appear to be frequent, and hepatotoxicity is uncommon to rare. Randomized controlled trials are needed to evaluate the safety and efficacy of cyproheptadine before authorization for appetite stimulation, especially in young children as studies at this age are lacking. Possible hepatic complications should be monitored, as very rare cases of liver failure have been reported.
Published: 2021
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3. Oxidative stress activates red cell adhesion to laminin in sickle cell disease

Author: Maria Alejandra, Lizarralde-Iragorri, Sophie D, Lefevre, Sylvie, Cochet, Sara, El Hoss, Valentine, Brousse, Anne, Filipe, Michael, Dussiot, Slim, Azouzi, Caroline, Le Van Kim, Fernando, Rodrigues-Lima, Olivier, Français, Bruno, Le Pioufle, Thomas, Klei, Robin, van Bruggen, Wassim, El Nemer, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université de Paris (UP), Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Electronique, Systèmes de communication et Microsystèmes (ESYCOM), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre National de la Recherche Scientifique (CNRS)-Université Gustave Eiffel, Institut d'Alembert (IDA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), Université Paris-Saclay, Laboratoire Lumière, Matière et Interfaces (LuMIn), CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), Sanquin Research, University of Amsterdam [Amsterdam] (UvA), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Gustave Eiffel, Le Pioufle, Bruno, and AII - Inflammatory diseases
Subjects: Sickle Cell Disease, Erythrocytes, [SPI.NANO] Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, Red Cells, hemic and immune systems, Red Cell Adhesion, Anemia, Sickle Cell, Lutheran Blood-Group System, Article, Hemoglobinopathies, Oxidative Stress, hemic and lymphatic diseases, Cell Adhesion, Humans, Laminin, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, Cell Adhesion Molecules
Abstract: International audience; Vaso-occlusive crises are the hallmark of sickle cell disease (SCD). They are believed to occur in two steps, starting with adhesion of deformable low-dense red blood cells (RBCs), or other blood cells such as neutrophils, to the wall of post-capillary venules, followed by trapping of the denser RBCs or leukocytes in the areas of adhesion because of reduced effective lumen-diameter. In SCD, RBCs are heterogeneous in terms of density, shape, deformability and surface proteins, which accounts for the differences observed in their adhesion and resistance to shear stress. Sickle RBCs exhibit abnormal adhesion to laminin mediated by Lu/BCAM protein at their surface. This adhesion is triggered by Lu/BCAM phosphorylation in reticulocytes but such phosphorylation does not occur in mature dense RBCs despite firm adhesion to laminin. In this study, we investigated the adhesive properties of sickle RBC subpopulations and addressed the molecular mechanism responsible for the increased adhesion of dense RBCs to laminin in the absence of Lu/BCAM phosphorylation. We provide evidence for the implication of oxidative stress in post-translational modifications of Lu/BCAM that impact its distribution and cis-interaction with glycophorin C at the cell surface activating its adhesive function in sickle dense RBCs.
Published: 2020
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4. One-Fifth of Children with Sickle Cell Anemia Show Exercise-Induced Hemoglobin Desaturation: Rate of Perceived Exertion and Role of Blood Rheology

Author: Corinne Pondarré, Helene Bourdeau, Keyne Charlot, Benedicte Boutonnat-Faucher, Cécile Arnaud, David Grevent, Annie Kamden, Philippe Connes, Suzanne Verlhac, Lydie Da Costa, Mariane de Montalembert, Valentine Brousse, Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS), CHI Créteil, Service d'Hématologie Biologique [Hôpital Robert Debré, Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Institut de Recherche Biomédicale des Armée [Brétigny/Orge] (IRBA), CHU Necker - Enfants Malades [AP-HP], Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: medicine.medical_specialty, lcsh:Medicine, Perceived exertion, 030204 cardiovascular system & hematology, Article, Hypoxemia, 03 medical and health sciences, 0302 clinical medicine, children, Internal medicine, Heart rate, medicine, In patient, Exertion, 10. No inequality, ComputingMilieux_MISCELLANEOUS, hypoxemia, six-minute walk test, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, lcsh:R, General Medicine, medicine.disease, Sickle cell anemia, Red blood cell, medicine.anatomical_structure, Cardiology, sickle cell disease, Hemoglobin, medicine.symptom, business, 030215 immunology
Abstract: Perceived exertion is an important self-limiting factor influencing functional capacity in patients with sickle cell anemia (SCA). Exercise-related hemoglobin desaturation (EHD) may occur during a six-minute walking test (6MWT) and could influence the perceived rate of exertion. The aims of this study were (1) to compare the 6MWT responses (heart rate, perceived rate of exertion, and distance covered) between SCA children with and without EHD, and (2) to test the associations between EHD and several biological/physiological parameters. Nine of 51 SCA children (18%) at steady state (mean age 11.9 &plusmn, 3.8 years) exhibited EHD at the end of the 6MWT. The rate of perceived exertion increased with exercise in the two groups, but reached higher values in the EHD group. Heart rate and performance during the 6MWT did not differ between the two groups. The magnitude of change in SpO2 during the 6MWT was independently associated with the red blood cell (RBC) deformability and RBC aggregates strength. This study demonstrates that SCA children with EHD during a 6MWT have a higher rate of perceived exertion than non-EHD children despite a similar physiological demand, and that abnormal RBC rheology determinants appear to be significant contributors.
Published: 2019
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5. Functional Vision Analysis in Patients With CHARGE Syndrome

Author: Georges Challe, Véronique Abadie, Gilles C Martin, Nhung T H Trinh, Tania Attié-Bitach, Matthieu P. Robert, Bahram Bodaghi, Dominique Bremond-Gignac, Fondation Ophtalmologique Adolphe de Rothschild [Paris], Sorbonne Université (SU), Cognition and Action Group (COGNAC-G - UMR 8257), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service d'ophtalmologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Ophtalmologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service de Génétique Médicale [CHU Necker], Université de Paris - UFR Sciences Fondamentales et Biomédicales [Sciences], Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de pédiatrie générale [CHU Necker], CB - Centre Borelli - UMR 9010 (CB), Service de Santé des Armées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay)-Université Paris Cité (UPCité), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Paris Cité - UFR Sciences Fondamentales et Biomédicales [Sciences], Université Paris Cité (UPCité), and Gestionnaire, Hal Sorbonne Université
Subjects: Male, medicine.medical_specialty, Visual acuity, genetic structures, Adolescent, Vision Disorders, Visual Acuity, Fundus (eye), 03 medical and health sciences, CHARGE syndrome, Young Adult, 0302 clinical medicine, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, 030225 pediatrics, Ophthalmology, Surveys and Questionnaires, Activities of Daily Living, Medicine, Humans, In patient, Prospective Studies, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Strabismus, Child, Coloboma, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Functional vision, business.industry, General Medicine, medicine.disease, eye diseases, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Atresia, Pediatrics, Perinatology and Child Health, 030221 ophthalmology & optometry, Female, medicine.symptom, CHARGE Syndrome, business
Abstract: Purpose: To evaluate functional vision in patients with CHARGE syndrome (coloboma, heart defects, atresia of the choanae, retardation of growth and development, genital and urinary anomalies, and ear anomalies) by using a new questionnaire entitled VISIOCHARGE. Methods: Ophthalmological data including fundus description and visual acuity, when available, were extracted from the charts of 83 patients with CHARGE syndrome, and the VISIOCHARGE questionnaire was prospectively mailed to 55 of those patients. The answers from the 36 responders (18 males) allowed for the calculation of three scores that assessed distance vision, near vision, and overall ability scores. Results: Visual acuity measurements were extracted from the charts of 20 of the 36 patients. The mean visual acuity was 20/50. The mean distance vision score of 0.62 ± 0.30 and near vision score of 0.78 ± 0.23 were correlated with visual acuity in the 20 patients (ρ = 0.64, P = .002 and ρ = 0.61, P = .005, respectively) and were associated with the severity of colobomatous malformation ( P = .049 and P = .008, respectively). Severity of the ocular malformation was not associated with the overall ability score ( P = .64). Conclusions: The VISIOCHARGE questionnaire is feasible for patients with CHARGE syndrome and may help in the assessment of visual function. The mean visual acuity and answers to the VISIOCHARGE questionnaire showed relatively good visual skills in patients with CHARGE syndrome in everyday life, even in those with bilateral colobomas, which contrasts with the pessimistic conclusions usually resulting from the initial fundus examination. [ J Pediatr Ophthalmol Strabismus . 2020;57(2):120–128.]
Published: 2019
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6. Association of Matched-Sibling Donor Hematopoietic Stem Cell Transplantation with Transcranial-Doppler Velocities in Children with Sickle Cell Anemia

Author: Françoise Bernaudin, Monique Elmaleh-Bergès, Charlotte Jubert, Olivier Taïeb, Elisabeth Ducros-Miralles, Camille Runel, Eleonore Petras, Catherine Paillard, Corinne Guitton, Claire Galambrun, Aurore Malric, Emmanuella Leveillé, Valentine Brousse, Jean-Hugues Dalle, Isabelle Thuret, Régis Peffault de Latour, Gérard Socié, Gisèle Elana, Annie Kamdem, Suzanne Verlhac, Manuela Vasile, Benedicte Neven, Lydia Divialle-Doumdo, Sylvie Chevret, Florence Missud, Elise Drain, Corinne Pondarré, Cécile Arnaud, Centre Hospitalier Intercommunal de Créteil (CHIC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Robert Debré Paris, Hôpital Robert Debré, Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de pédiatrie, d'hématologie et d'oncologie [Hôpital de La Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'immuno-hématologie pédiatrique [CHU Necker], Aix Marseille Université (AMU), Hôpital de Hautepierre [Strasbourg], Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, CHI Créteil, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Bordeaux [Bordeaux], CHU de la Martinique [Fort de France], Service de psychopathologie de l'enfant et de l'adolescent, psychiatrie générale [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint Louis [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-CHU Saint Louis [APHP], Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut national du cancer [Boulogne] (INCA)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint Louis [APHP]-Institut national du cancer [Boulogne] (INCA), and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)
Subjects: Male, Blood transfusion, Transplantation Conditioning, Ultrasonography, Doppler, Transcranial, medicine.medical_treatment, Graft vs Host Disease, Hematopoietic stem cell transplantation, 01 natural sciences, hydroxyurea, 0302 clinical medicine, 030212 general & internal medicine, Child, Stroke, Original Investigation, transfusions, Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, Allografts, Tissue Donors, Sickle cell anemia, 3. Good health, extracranial internal carotid artery Doppler sonography, Cerebrovascular Circulation, HSCT, Female, Blood Flow Velocity, medicine.medical_specialty, Anemia, Sickle Cell, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, cerebral MRI/MRA, Internal medicine, medicine, ischemic stroke, Humans, 0101 mathematics, Sibling, Propensity Score, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, transcranial Doppler imaging, business.industry, Siblings, 010102 general mathematics, medicine.disease, Transcranial Doppler, Transplantation, Propensity score matching, Ferritins, Quality of Life, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: IMPORTANCE: In children with sickle cell anemia (SCA), high transcranial Doppler (TCD) velocities are associated with stroke risk, which is reduced by chronic transfusion. Whether matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) can reduce velocities in patients with SCA is unknown. OBJECTIVE: To determine the association of MSD-HSCT with TCD velocities as a surrogate for the occurrence of ischemic stroke in children with SCA. DESIGN, SETTING, AND PARTICIPANTS: Nonrandomized controlled intervention study conducted at 9 French centers. Patients with SCA were enrolled between December 2010 and June 2013, with 3-year follow-up ending in January 2017. Children with SCA were eligible if younger than 15 years, required chronic transfusions for persistently elevated TCD velocities, and had at least 1 sibling without SCA from the same 2 parents. Families agreed to HLA antigen typing and transplantation if a matched sibling donor was identified or to standard care in the absence of a matched sibling donor. EXPOSURES: MSD-HSCT (n = 32), compared with standard care (n = 35) (transfusions for ≥1 year with potential switch to hydroxyurea thereafter), using propensity score matching. MAIN OUTCOMES AND MEASURES: The primary outcome was the highest time-averaged mean of maximum velocities in 8 cerebral arteries, measured by TCD (TCD velocity) at 1 year. Twenty-five of 29 secondary outcomes were analyzed, including the highest TCD velocity at 3 years and normalization of velocities (
Published: 2019
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7. Prognostic factors of disease severity in infants with sickle cell anemia: A comprehensive longitudinal cohort study

Author: Pierre A. Buffet, Narla Mohandas, Valentine Brousse, Véronique Picard, Caroline Le Van Kim, Catia Pereira, Corinne Guitton, Chantal Brouzes, Sara El Hoss, Cécile Arnaud, Claudine Lapoumeroulie, Stephan Menzel, Thao Nguyen-Khoa, Wassim El Nemer, Mariane de Montalembert, Kate Gardner, Serge Pissard, Yves Colin-Aronovicz, Béatrice Pellegrino, Marie Hélène Odièvre-Montanié, Micheline Maier-Redelsperger, Françoise Bernaudin, Caroline Elie, Naïm Bouazza, David Mames, Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CIC - Mère Enfant Necker Cochin Paris Centre (CIC 1419), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHI Créteil, Service de pédiatrie, CHI Poissy-Saint-Germain, Service d'hématologie, immunologie biologiques et cytogénétique, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Laboratory of molecular mechanisms of hematologic disorders and therapeutic implications (ERL 8254 - Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), 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), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association, Institut National de la Transfusion Sanguine [Paris] (INTS), Université Pierre et Marie Curie - Paris 6 (UPMC), Red Cell Physiology Laboratory [New York, USA], New York Blood Center, 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), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche sur l'architecture antique (IRAA), Université Lumière - Lyon 2 (UL2)-Aix Marseille Université (AMU)-Université de Pau et des Pays de l'Adour (UPPA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS), Forschungszentrum Jülich GmbH, CHU Cochin [AP-HP], Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Pau et des Pays de l'Adour (UPPA)-Sorbonne Université (SU)-Université Lumière - Lyon 2 (UL2)-Aix Marseille Université (AMU), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10
Subjects: Male, medicine.medical_specialty, Blood transfusion, Anemia, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Anemia, Sickle Cell, Severity of Illness Index, Cohort Studies, Hemoglobins, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Severity of illness, Fetal hemoglobin, Humans, Medicine, Blood Transfusion, Longitudinal Studies, Fetal Hemoglobin, ComputingMilieux_MISCELLANEOUS, Univariate analysis, business.industry, Infant, Hematology, Prognosis, medicine.disease, Sickle cell anemia, 3. Good health, Hospitalization, 030220 oncology & carcinogenesis, Cohort, Female, business, Biomarkers, 030215 immunology, Cohort study
Abstract: In order to identify very early prognostic factors that can provide insights into subsequent clinical complications, we performed a comprehensive longitudinal multi-center cohort study on 57 infants with sickle cell anemia (55 SS; 2 Sβ°) during the first 2 years of life (ClinicalTrials.gov: NCT01207037). Time to first occurrence of a severe clinical event-acute splenic sequestration (ASS), vaso-occlusive (VOC) event requiring hospitalization, transfusion requirement, conditional/ abnormal cerebral velocities, or death-was used as a composite endpoint. Infants were recruited at a mean age of 4.4 ±1 months. Median follow-up was 19.4 months. During the study period, 38.6% of infants experienced ≥1 severe event: 14% ASS, 22.8% ≥ 1 VOC (median age: 13.4 and 12.8 months, respectively) and 33.3% required transfusion. Of note, 77% of the cohort was hospitalized, with febrile illness being the leading cause for admission. Univariate analysis of various biomarkers measured at enrollment showed that fetal hemoglobin (HbF) was the strongest prognostic factor of subsequent severe outcome. Other biomarkers measured at enrolment including absolute neutrophil or reticulocyte counts, expression of erythroid adhesion markers, % of dense red cells, cellular deformability or ϒ-globin genetic variants, failed to be associated with severe clinical outcome. Multivariate analysis demonstrated that higher Hb concentration and HbF level are two independent protective factors (adjusted HRs (95% CI) 0.27 (0.11-0.73) and 0.16 (0.06-0.43), respectively). These findings imply that early measurement of HbF and Hb levels can identify infants at high risk for subsequent severe complications, who might maximally benefit from early disease modifying treatments.
Published: 2018
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8. Chromosome 14q32.2 Imprinted Region Disruption as an Alternative Molecular Diagnosis of Silver-Russell Syndrome

Author: Sylvie Rossignol, Walid Abi Habib, Sophie Geoffron, Salah Azzi, Béatrice Dubern, Sandra Chantot-Bastaraud, Isabelle Oliver Petit, Thuy-Ai Vu-Hong, Marie-Noelle Dufourg, Ana Pinheiro Machado Canton, Catherine Pienkowski, Jennifer Salem, Blandine Esteva, Fanny Morice Picard, Bertrand Isidor, Nicole Philip, Frédéric Brioude, Alexandra Afenjar, Julien Thevenon, David Geneviève, Mélanie Fradin, Marlène Rio, Catherine Naud-Saudreau, Irène Netchine, Maithé Tauber, Christel Chalouhi, Tiffanny Busa, Virginie Steunou, Eloise Giabicani, Solveig Heide, Agnès Linglart, Madeleine D. Harbison, 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), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Universidade de São Paulo Medical School (FMUSP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], 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 ), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Montpellier, Université de Montpellier (UM), Centre hospitalier universitaire de Nantes (CHU Nantes), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Thérapie génique, Génomique et Epigénomique (U 1169), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Bretagne Sud - Lorient (UBS Lorient), Université de Bretagne Sud (UBS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Génétique Médicale [CHU Necker], Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Axe 3 : organisation structurale multiéchelle des matériaux (SPCTS-AXE3), Science des Procédés Céramiques et de Traitements de Surface (SPCTS), Université de Limoges (UNILIM)-Ecole Nationale Supérieure de Céramique Industrielle (ENSCI)-Institut des Procédés Appliqués aux Matériaux (IPAM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Ecole Nationale Supérieure de Céramique Industrielle (ENSCI)-Institut des Procédés Appliqués aux Matériaux (IPAM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de Référence du Syndrome de Prader-Willi, Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Unité de recherche sur les maladies cardiovasculaires et métaboliques, UMR S 1166, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité Fonctionnelle de Génétique Clinique [CHU Pitié Salpétrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rennes 1 (UR1), 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 ), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'ORL et de Chirurgie Cervicofaciale, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Hôpital des Enfants, CHU Toulouse [Toulouse], Institut des Procédés Appliqués aux Matériaux (IPAM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Ecole Nationale Supérieure de Céramique Industrielle (ENSCI)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Institut des Procédés Appliqués aux Matériaux (IPAM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Ecole Nationale Supérieure de Céramique Industrielle (ENSCI)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM), Service de Génétique et d'Embryologie Médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Unité Fonctionnelle de Génétique Clinique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP]-Centre de référence 'Déficiences Intellectuelles de Causes Rares' - Paris-Groupe de Recherche Clinique 'Déficience Intellectuelle et Autisme' - Paris, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Ined Inserm joint unit Elfe, Hôpital Arnaud de Villeneuve, Département de génétique médicale, maladies rares et médecine personnalisée [CHRU de Montpellier], Groupe de Recherche Clinique : Déficience Intellectuelle et Autisme (GRC), Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'endocrinologie et diabétologie pédiatriques - Le Kremlin-Bicêtre, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and MAGIC Foundation
Subjects: 0301 basic medicine, Oncology, Male, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Puberty, Precocious, Chromosome Disorders, Biochemistry, Pubarche, Endocrinology, Young adult, Child, 2. Zero hunger, MEG3, Syndrome, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Uniparental disomy, 3. Good health, Phenotype, Child, Preschool, DNA methylation, Intercellular Signaling Peptides and Proteins, Female, RNA, Long Noncoding, Chromosome Deletion, Adult, medicine.medical_specialty, Adolescent, Diagnosis, Differential, 03 medical and health sciences, Genomic Imprinting, Young Adult, Internal medicine, parasitic diseases, medicine, Humans, Retrospective Studies, Chromosomes, Human, Pair 14, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, Silver–Russell syndrome, Biochemistry (medical), Calcium-Binding Proteins, Chromosome, Membrane Proteins, DNA Methylation, Uniparental Disomy, medicine.disease, Silver-Russell Syndrome, 030104 developmental biology, business, Body mass index
Abstract: International audience; Context - Silver-Russell syndrome (SRS) (mainly secondary to 11p15 molecular disruption) and Temple syndrome (TS) (secondary to 14q32.2 molecular disruption) are imprinting disorders with phenotypic (prenatal and postnatal growth retardation, early feeding difficulties) and molecular overlap. Objective - To describe the clinical overlap between SRS and TS and extensively study the molecular aspects of TS. Patients - We retrospectively collected data on 28 patients with disruption of the 14q32.2 imprinted region, identified in our center, and performed extensive molecular analysis. Results - Seventeen (60.7%) patients showed loss of methylation of the MEG3/DLK1 intergenic differentially methylated region by epimutation. Eight (28.6%) patients had maternal uniparental disomy of chromosome 14 and three (10.7%) had a paternal deletion in 14q32.2. Most patients (72.7%) had a Netchine-Harbison SRS clinical scoring system ≥4/6, and consistent with a clinical diagnosis of SRS. The mean age at puberty onset was 7.2 years in girls and 9.6 years in boys; 37.5% had premature pubarche. The body mass index of all patients increased before pubarche and/or the onset of puberty. Multilocus analysis identified multiple methylation defects in 58.8% of patients. We identified four potentially damaging genetic variants in genes encoding proteins involved in the establishment or maintenance of DNA methylation. Conclusions - Most patients with 14q32.2 disruption fulfill the criteria for a clinical diagnosis of SRS. These clinical data suggest similar management of patients with TS and SRS, with special attention to their young age at the onset of puberty and early increase of body mass index.
Published: 2018
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9. Fulminant Nocardiosis Due to a Multidrug-Resistant Isolate in a 12-Year-Old Immunocompetent Child

Author: Olivia Senard, Olivier Lortholary, Olivier Join-Lambert, Stéphane Blanot, Grégory Jouvion, Julie Toubiana, Veronica Rodriguez-Nava, Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de neurochirurgie pédiatrique [CHU Necker], Centre Médical de l'Institut Pasteur (CMIP), Institut Pasteur [Paris] (IP), Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Microbiologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre Médical de l'Institut Pasteur, Institut Pasteur [Paris], Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), CHU Necker - Enfants Malades [AP-HP], Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Ecole Nationale Vétérinaire de Lyon (ENVL), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris]
Subjects: 0301 basic medicine, Male, Abdominal pain, Pediatrics, medicine.medical_specialty, Fulminant, 030106 microbiology, Nocardia Infections, Nocardia, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Fatal Outcome, 030225 pediatrics, Drug Resistance, Multiple, Bacterial, medicine, Humans, Medical history, Abscess, Child, biology, business.industry, Nocardiosis, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Abdominal mass, 3. Good health, Anti-Bacterial Agents, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Pediatrics, Perinatology and Child Health, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Drug Therapy, Combination, medicine.symptom, business, Immunocompetence
Abstract: International audience; Nocardiosis is a rare cause of infection that usually affects immunocompromised adult patients and might not be recognized by pediatricians. We report a fatal case of disseminated nocardiosis in a previously healthy child initially admitted for an abdominal mass with suspicion of a renal malignant tumor. The patient, originating from Mali without any medical history, displayed abdominal pain with progressive altered general status. Laboratory and imaging findings revealed lymphocytic meningitis and disseminated abscesses in the brain and the cerebellum and a large number of cystic lesions of the kidney. Despite being administered wide-spectrum antibiotics and antituberculous and antifungal therapies with an external ventricular drainage for intracranial hypertension, the patient died 6 days after his admission. Nocardia spp was cultured from a renal biopsy and the cerebrospinal fluid. Species identification and antibiotic susceptibility were obtained later, revealing a multidrug-resistant isolate of the Nocardia elegans/aobensis/africana complex. This case reveals the difficulties of diagnosing nocardiosis, in particular in children not known to be immunocompromised, because we face multiple differential diagnoses and the importance of treating nocardiosis appropriately because of intrinsic resistance issues.
Published: 2018
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10. Supplementary data to: Algorithms to define abnormal growth in children: external validation and head-to-head 3 comparison 4 5

Author: Scherdel, Pauline, Matczak, Soraya, Leger, Juliane, Martinez-Vinson, Christine, Brauner, Raja, Nicklaus, Sophie, Resche-Rigon, Matthieu, Heude, Barbara, Duchange, Nathalie, Equipe 6 : ORCHAD - Origines précoces de la santé du développement de l'enfant (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Endocrinologie et Diabétologie Pédiatriques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Centre de référence ds maladies endocriniennes de la croissance et du développement, Service de gastroentérologie et nutrition pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Unité d'endocrinologie pédiatrique, Université Paris Descartes - Paris 5 (UPD5)-Fondation Ophtalmologique Adolphe de Rothschild [Paris], Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), Université Paris Diderot - Paris 7 (UPD7)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Sorbonne Paris Cité (USPC), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré, and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)
Subjects: [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
Abstract: Suplemental Tables 1, 2 and 3. Supplemental Fig.1 and Fig.2 Article published in J Clin Endocrinol Metab. 2018 Aug 20. doi: 10.1210/jc.2018-00723
Published: 2018

11. A microfluidic approach to study the effect of mechanical stress on erythrocytes in sickle cell disease

Author: Maria Alejandra Lizarralde Iragorri, Bruno Le Pioufle, Alexander Rodrigo Ferreira, Jacques Elion, Ana Cristina Silva Pinto, Claudine Lapoumeroulie, Yann Lamarre, Tieying Xu, Simone Kashima, Valentine Brousse, Dimas Tadeu Covas, Sara El Hoss, Wassim El Nemer, Yves Colin, Olivier Français, Caroline Le Van Kim, Sophie D. Lefevre, Michael Dussiot, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS), Institut National de la Transfusion Sanguine [Paris] (INTS), Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bio-MIcroSystèmes et BioSensors (SATIE-BIOMIS), Systèmes d'Information et d'Analyse Multi-Echelles (SIAME), Systèmes et Applications des Technologies de l'Information et de l'Energie (SATIE), École normale supérieure - Rennes (ENS Rennes)-Université Paris-Sud - Paris 11 (UP11)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Cachan (ENS Cachan)-Université Gustave Eiffel (UNIV GUSTAVE EIFFEL)-École normale supérieure - Rennes (ENS Rennes)-Université Paris-Sud - Paris 11 (UP11)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Cachan (ENS Cachan)-Université Gustave Eiffel (UNIV GUSTAVE EIFFEL)-Systèmes et Applications des Technologies de l'Information et de l'Energie (SATIE), Université Paris-Seine-Université Paris-Seine-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Cachan (ENS Cachan)-Université Gustave Eiffel (UNIV GUSTAVE EIFFEL), Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), Institut d'Alembert (IDA), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Cachan (ENS Cachan), Universidade de São Paulo (USP), Protéines de la membrane érythrocytaire et homologues non-érythroides, Université des Antilles et de la Guyane (UAG)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), ESIEE Paris, Electronique, Systèmes de communication et Microsystèmes (ESYCOM), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Paris-Est Marne-la-Vallée (UPEM)-ESIEE Paris, Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Systèmes d'Information et d'Analyse Multi-Echelles (SATIE-SIAME), École normale supérieure - Cachan (ENS Cachan)-Université Paris-Sud - Paris 11 (UP11)-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-École normale supérieure - Rennes (ENS Rennes)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-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)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Cachan (ENS Cachan)-Université Paris-Sud - Paris 11 (UP11)-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-École normale supérieure - Rennes (ENS Rennes)-Université de Cergy Pontoise (UCP), 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)-Centre National de la Recherche Scientifique (CNRS), Universidade de São Paulo = University of São Paulo (USP), 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 Paris-Est Marne-la-Vallée (UPEM)-ESIEE Paris, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Seine-Université Paris-Seine-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Cachan (ENS Cachan)-Université Paris-Sud - Paris 11 (UP11)-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-École normale supérieure - Rennes (ENS Rennes)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre National de la Recherche Scientifique (CNRS)-Systèmes et Applications des Technologies de l'Information et de l'Energie (SATIE), and Université Paris-Seine-Université Paris-Seine-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, 0301 basic medicine, Erythrocytes, Lysis, Adolescent, Cell, Biomedical Engineering, Bioengineering, Anemia, Sickle Cell, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biochemistry, Young Adult, 03 medical and health sciences, Erythrocyte Deformability, Lab-On-A-Chip Devices, medicine, Humans, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, Child, ComputingMilieux_MISCELLANEOUS, Red Cell, Chemistry, Point mutation, General Chemistry, Middle Aged, Hypoxia (medical), Biomechanical Phenomena, Cell biology, Red blood cell, 030104 developmental biology, medicine.anatomical_structure, Membrane protein, Child, Preschool, Female, Stress, Mechanical, medicine.symptom, Intracellular
Abstract: The human red blood cell is a biconcave disc of 6-8 × 2 μm that is highly elastic. This capacity to deform enables it to stretch while circulating through narrow capillaries to ensure its main function of gas exchange. Red cell shape and deformability are altered in membrane disorders because of defects in skeletal or membrane proteins affecting protein-protein interactions. Red cell properties are also altered in other pathologies such as sickle cell disease. Sickle cell disease is a genetic hereditary disorder caused by a single point mutation in the β-globin gene generating sickle haemoglobin (HbS). Hypoxia drives HbS polymerisation that is responsible for red cell sickling and reduced deformability. The main clinical features of sickle cell disease are vaso-occlusive crises and haemolytic anaemia. Foetal haemoglobin (HbF) inhibits HbS polymerisation and positively impacts red cell survival in the circulation but the mechanism through which it exerts this action is not fully characterized. In this study, we designed a microfluidic biochip mimicking the dimensions of human capillaries to measure the impact of repeated mechanical stress on the survival of red cells at the single cell scale under controlled pressure. We show that mechanical stress is a critical parameter underlying intravascular haemolysis in sickle cell disease and that high intracellular levels of HbF protect against lysis. The biochip is a promising tool to address red cell deformability in pathological situations and to screen for molecules positively impacting this parameter in order to improve red cell survival in the circulation.
Published: 2018
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12. Design of the DREPAGREFFE trial: A prospective controlled multicenter study evaluating the benefit of genoidentical hematopoietic stem cell transplantation over chronic transfusion in sickle cell anemia children detected to be at risk of stroke by transcranial Doppler (NCT 01340404)

Author: Sylvie Chevret, Suzanne Verlhac, Elisabeth Ducros-Miralles, Jean-Hugues Dalle, Regis Peffault de Latour, Mariane de Montalembert, Malika Benkerrou, Corinne Pondarré, Isabelle Thuret, Corinne Guitton, Emmanuelle Lesprit, Maryse Etienne-Julan, Gisèle Elana, Jean-Pierre Vannier, Patrick Lutz, Bénédicte Neven, Claire Galambrun, Catherine Paillard, Camille Runel, Charlotte Jubert, Cécile Arnaud, Annie Kamdem, Valentine Brousse, Florence Missud, Marie Petras, Lydia Doumdo-Divialle, Claire Berger, Françoise Fréard, Olivier Taieb, Elise Drain, Monique Elmaleh, Manuela Vasile, Yacine Khelif, Myriam Bernaudin, Philippe Chadebech, France Pirenne, Gérard Socié, Françoise Bernaudin, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Intercommunal de Créteil (CHIC), Hôpital Robert Debré, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Centre Léon Bérard [Lyon], Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris-Sud - Paris 11 (UP11), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université des Antilles (UA), CHU Pointe-à-Pitre/Abymes [Guadeloupe], CHU de la Martinique [Fort de France], Hôpital Charles Nicolle [Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpital de Hautepierre [Strasbourg], Université de Strasbourg (UNISTRA), CHU Bordeaux [Bordeaux], Université de Bordeaux (UB), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Université de Saint-Etienne, Hôpital Avicenne [AP-HP], Université Paris 13 (UP13), Université de Caen Normandie (UNICAEN), Etablissement Français du Sang [Île-de-France Mondor], IMRB - 'Transfusion et Maladies du Globule Rouge' [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), Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de Radiologie [Créteil], CHI Créteil, Hôpital Robert Debré Paris, Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de pédiatrie, d'hématologie et d'oncologie [Hôpital de La Timone - APHM], Service d'hématologie, immunologie biologiques et cytogénétique, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurologie [CHU Pointe à Pitre], CHU Fort de France, Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique], Micro-Environnement et Régulation Cellulaire Intégrée (MERCI), Normandie Université (NU)-Normandie Université (NU), Service d'immuno-hématologie pédiatrique [CHU Necker], Laboratoire d'hématologie biologique [Hôpital de la Timone - Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Groupe hospitalier Pellegrin, Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Rouen, CHADEBECH, Philippe, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Université Jean Monnet - Saint-Étienne (UJM), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Saint Louis [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Service d'Hématologie et Oncologie pédiatriques, Hôpital Trousseau [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Hôpital Avicenne, Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: Male, Pediatrics, Ultrasonography, Doppler, Transcranial, medicine.medical_treatment, Hematopoietic stem cell transplantation, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Cognition, 0302 clinical medicine, Genetic randomization, Medicine, Pharmacology (medical), Prospective Studies, Child, Prospective cohort study, Stroke, General Medicine, Sickle cell anemia, 3. Good health, Cerebral vasculopathy, Research Design, Child, Preschool, 030220 oncology & carcinogenesis, Female, medicine.medical_specialty, Iron Overload, Randomization, Adolescent, Anemia, Sickle Cell, Chronic transfusion, 03 medical and health sciences, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Humans, Blood Transfusion, Adverse effect, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Transfusion Reaction, Transcranial Doppler, medicine.disease, Surgery, Transplantation, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Quality of Life, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, 030215 immunology
Abstract: Background Children with sickle cell anemia (SCA) have an 11% risk of stroke by the age of 18. Chronic transfusion applied in patients detected to be at risk by transcranial Doppler allows a significant reduction of stroke risk. However, chronic transfusion exposes to several adverse events, including alloimmunization and iron overload, and is not curative. Hematopoietic stem cell transplantation allows termination of the transfusion program, but its benefit has not been demonstrated. Design DREPAGREFFE ( NCT01340404 ) is a multicenter, prospective trial enrolling SCA children younger than 15 years receiving chronic transfusion due to a history of abnormal transcranial Doppler (velocities ≥ 200 cm/s). Only those with at least one non-SCA sibling and parents accepting HLA-typing and transplantation with a genoidentical donor were eligible. Chronic transfusion was pursued in patients with no available donor, whereas others were transplanted. Comparison between the 2 arms (transfusion vs transplantation) was analyzed using both genetic randomization and propensity-score matching as a sensitivity analysis. The primary end-point was the velocity measure at 1 year. Secondary endpoints were the incidence of stroke, silent cerebral infarcts and stenoses, cognitive performance in comparison with siblings, allo-immunization, iron-overload, phosphatidyl-serine, angiogenesis/hypoxia, brain injury-related factor expression, quality of life and cost. Objectives To show that genoidentical transplantation decreases velocities significantly more than chronic transfusion in SCA children at risk of stroke. Discussion DREPAGREFFE is the first prospective study to evaluate transplantation in SCA children. It compares the outcome of cerebral vasculopathy following genoidentical transplantation versus chronic transfusion using genetic randomization and causal inference methods.
Published: 2017
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13. Cardiac iron overload in chronically transfused patients with thalassemia, sickle cell anemia, or myelodysplastic syndrome

Author: Amandine Baptiste, Thibaud Lefebvre, Olivier Ernst, Emmanuelle Chauzit, Jean-Pierre Vannier, Agnès Guerci-Bresler, Christian Rose, Zoubida Karim, Hervé Puy, Aspasia Stamatoullas, Mariane De Montalembert, Valentine Brousse, Krimo Bouabdallah, Mohamed Touati, C. Dumesnil, Agnès Lahary, Marina Cavazzana, Caroline Elie, Jean-Antoine Ribeil, Service de pédiatrie générale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Centre de Référence de la Drépanocytose-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service d'Hématologie Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Hématologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Micro-Environnement et Régulation Cellulaire Intégrée (MERCI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), Hôpital Charles Nicolle [Rouen], Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Département de Biothérapie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], CHU Bordeaux [Bordeaux], Hôpital Cochin [AP-HP], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'informatique médicale et biostatistiques [CHU Necker], Radiologie interventionnelle, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie, Hôpital Saint-Vincent-de-Paul, TAN, Yossan-Var, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre de Référence de la Drépanocytose, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (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)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, Blood transfusion, Physiology, Thalassemia, medicine.medical_treatment, [SDV]Life Sciences [q-bio], lcsh:Medicine, 030204 cardiovascular system & hematology, Gastroenterology, Physical Chemistry, Biochemistry, Diagnostic Radiology, 0302 clinical medicine, hemic and lymphatic diseases, Medicine and Health Sciences, Erythropoiesis, 10. No inequality, Child, lcsh:Science, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Chelation, Radiology and Imaging, Heart, Hematology, Middle Aged, Magnetic Resonance Imaging, Sickle cell anemia, Clinical Laboratory Sciences, 3. Good health, [SDV] Life Sciences [q-bio], Chemistry, Genetic Diseases, 030220 oncology & carcinogenesis, Physical Sciences, Female, Anatomy, Research Article, Adult, medicine.medical_specialty, Iron Overload, Adolescent, Anemia, Imaging Techniques, Iron, Anemia, Sickle Cell, Research and Analysis Methods, Iron Chelating Agents, 03 medical and health sciences, Autosomal Recessive Diseases, Hepcidin, Diagnostic Medicine, Internal medicine, medicine, Humans, Blood Transfusion, Clinical Genetics, Ferritin, Sickle Cell Disease, Chemical Bonding, business.industry, Transfusion Medicine, Myelodysplastic syndromes, Myocardium, lcsh:R, Biology and Life Sciences, Proteins, Protein Complexes, medicine.disease, Hematopoiesis, Hemoglobinopathies, Myelodysplastic Syndromes, biology.protein, Cardiovascular Anatomy, lcsh:Q, business, Physiological Processes, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: The risk and clinical significance of cardiac iron overload due to chronic transfusion varies with the underlying disease. Cardiac iron overload shortens the life expectancy of patients with thalassemia, whereas its effect is unclear in those with myelodysplastic syndromes (MDS). In patients with sickle cell anemia (SCA), iron does not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac iron overload, defined as a cardiovascular magnetic resonance T2*8 ECs in the past year, and age older than 6 years. We included from 9 centers 20 patients with thalassemia, 41 with SCA, and 25 with MDS in 2012-2014. Erythrocytapharesis did not consistently prevent iron overload in patients with SCA. Cardiac iron overload was found in 3 (15%) patients with thalassemia, none with SCA, and 4 (16%) with MDS. The liver iron content (LIC) ranged from 10.4 to 15.2 mg/g dry weight, with no significant differences across groups (P = 0.29). Abnormal T2* was not significantly associated with any of the measures of transfusion or chelation. Ferritin levels showed a strong association with LIC. Non-transferrin-bound iron was high in the thalassemia and MDS groups but low in the SCA group (P
Published: 2017
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14. Gene Therapy in a Patient with Sickle Cell Disease

Author: Bénédicte Neven, Emmanuel Payen, Olivier Negre, Yves Beuzard, Mariane de Montalembert, Pablo Bartolucci, Laure Caccavelli, Thibaud Lefebvre, Robert W. Ross, Laura Sandler, Philippe Leboulch, Stany Chrétien, Michaela Semeraro, Sandeep Soni, Hervé Puy, Salima Hacein-Bey-Abina, Stéphane Blanche, Gabor Istvan Veres, Jean-Antoine Ribeil, Wassim El Nemer, David Grevent, Jean-François Meritet, Philippe Bourget, Alessandra Magnani, Marina Cavazzana, Elisa Magrin, Leslie Weber, Département de Biothérapie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Centre d’Investigation Clinique en Biothérapies [CHU Pitié-Salpêtrière] (CIC-BT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Laboratoire d'Immunologie [AP-HP Hôpital Kremlin-Bicêtre] (GHU Paris-Sud), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Institut des Maladies Emergentes et des Thérapies Innovantes (IMETI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Commission de l'Energie Atomique et Alternative [Fontenay-aux-Roses], Université Paris-Sud - Paris 11 (UP11), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - Mère Enfant Necker Cochin Paris Centre (CIC 1419), 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), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 de Référence des Syndromes Drépanocytaires Majeurs [AP-HP Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), GR-Ex, Laboratoire d'Excellence, GR-Ex, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Cochin [AP-HP], Bluebird bio, Inc, Service de pédiatrie générale [CHU Necker], Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Ramathibodi Hospital [Bangkok, Thailand] (Mahidol University), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Centre d'investigation clinique Biothérapie [CHU Pitié-Salpêtrière] (CIC-BTi), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Université Paris Diderot - Paris 7 (UPD7)-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)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Payen, Emmanuel, Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-P 1421), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP]
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, 0301 basic medicine, Oncology, medicine.medical_specialty, Pathology, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Anemia, Genetic enhancement, 03 medical and health sciences, hemic and lymphatic diseases, Internal medicine, medicine, Bluebird Bio, Missense mutation, Adverse effect, ComputingMilieux_MISCELLANEOUS, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, medicine.disease, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, 3. Good health, Haematopoiesis, 030104 developmental biology, Stem cell, business, Busulfan, medicine.drug
Abstract: Sickle cell disease results from a homozygous missense mutation in the ß-globin gene that causes polymerization of hemoglobin S. Gene therapy for patients with this disorder is complicated by the complex cellular abnormalities and challenges in achieving effective, persistent inhibition of polymerization of hemoglobin S. We describe our first patient treated with lentiviral vector-mediated addition of an antisickling ß-globin gene into autologous hematopoietic stem cells. Adverse events were consistent with busulfan conditioning. Fifteen months after treatment, the level of therapeutic antisickling ß-globin remained high (approximately 50% of ß-like-globin chains) without recurrence of sickle crises and with correction of the biologic hallmarks of the disease. (Funded by Bluebird Bio and others; HGB-205 ClinicalTrials.gov number, NCT02151526 .).
Published: 2017
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15. A simplified, semi-quantitative structural lung disease computed tomography outcome during quiet breathing in infants with cystic fibrosis

Author: Magali Saguintaah, R Gauthier, Philippe Reix, Ikram Taleb Arrada, Nicolas Molinari, Laure Couderc, Cécile Duboibaudry, Stefan Matecki, Muriel Le Bourgeois, Raphaël Chiron, Yann Cabon, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Amiens-Picardie, CHRU de Brest - Département de Pédiatrie (CHU BREST Pédiatrie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de pédiatrie médicale et médecine de l'adolescent [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL), Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), 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 d'Investigation Clinique [Rouen] (CIC Rouen), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen]-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Hôpital Charles Nicolle [Rouen], and Normandie Université (NU)-Normandie Université (NU)-CHU Rouen
Subjects: Pulmonary and Respiratory Medicine, Lung Diseases, Male, medicine.medical_specialty, Concordance, Sedation, Chest tomography, Air trapping, Cystic fibrosis, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, 030212 general & internal medicine, Stage (cooking), Lung, ComputingMilieux_MISCELLANEOUS, Bronchiectasis, business.industry, Respiration, Reproducibility of Results, Infant, medicine.disease, 3. Good health, Surgery, medicine.anatomical_structure, Early Diagnosis, 030228 respiratory system, Lung disease, Research Design, Pediatrics, Perinatology and Child Health, Female, Radiology, medicine.symptom, business, Tomography, X-Ray Computed, Scoring
Abstract: International audience; Chest tomography (CT) using the controlled ventilation technique (CTCV) is a sensitive method to detect features of lung cystic fibrosis (CF) disease in infants with CF. However, this technique needs sedation and is not easily applied for the clinician who may need, in the follow-up, to evaluate more precisely lung disease in infants with CF. Thus, our study aims to evaluate if CT assessment of lung disease, without the need of sedation, during quiet breathing, using a semi-quantitative scoring system, is reproducible and may discriminate infants with CF from control infants at an early stage of the lung disease. 39 infants with CF underwent a first CT at 10.3 [9.4, 11.4] weeks of age. Among them, 33 underwent a second CT at 56.1 [53.1, 59.6] weeks of age. CF scoring images of the different scanner variables, i.e. bronchial wall thickening, bronchiectasis, mucus plugging and air trapping were compared to CT scoring obtained in 2 different groups of control infants of similar age without lung disease. Among all the constituents of the scoring, air trapping is the only parameter discriminating infants with CF from control infants at both ages in our study (p≤0.01). Moreover, air trapping explains 90% of the total score variability with r2=0.89 with a good concordance after re-scoring in blind, 6months apart, by the same operator for both infant populations: ICC=0.98 [0.97, 0.99]. In this study, we propose that CT during quiet breathing could be a useful clinical tool to evaluate the early presence of gas trapping in infants with CF.
Published: 2017
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16. Arterial Spin Labeling to Predict Brain Tumor Grading in Children: Correlations between Histopathologic Vascular Density and Perfusion MR Imaging

Author: Francis Brunelle, Thomas Blauwblomme, David Grevent, Christian Sainte-Rose, Pascale Varlet, Stéphanie Puget, Christelle Dufour, Mathilde Badoual, Nathalie Boddaert, Eimad Shotar, Mélanie Pagès, Volodia Dangouloff-Ros, Frantz Foissac, Raphael Calmon, Michel Zerah, Christophe Deroulers, Jacques Grill, Neuroimagerie en psychiatrie (U1000), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Imagerie et Modélisation en Neurobiologie et Cancérologie (IMNC (UMR_8165)), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Evaluation thérapeutique et pharmacologie périnatale et pédiatrique (EA_7323), Université Paris Descartes - Paris 5 (UPD5), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), PRES Sorbonne Paris Cité, Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP]
Subjects: Male, medicine.medical_specialty, Adolescent, Brain tumor, Contrast Media, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], Sensitivity and Specificity, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, medicine, Humans, Radiology, Nuclear Medicine and imaging, Child, Grading (tumors), ComputingMilieux_MISCELLANEOUS, Retrospective Studies, medicine.diagnostic_test, Brain Neoplasms, business.industry, Microvascular Density, Infant, Magnetic resonance imaging, medicine.disease, Confidence interval, Cerebral blood flow, Cerebrovascular Circulation, Child, Preschool, Female, Spin Labels, Radiology, Neoplasm Grading, Nuclear medicine, business, Perfusion, Magnetic Resonance Angiography, 030217 neurology & neurosurgery
Abstract: Purpose To compare arterial spin labeling (ASL) data between low- and high-grade brain tumors in children to establish a cutoff to distinguish low- from high-grade neoplasms and to assess potential correlations between cerebral blood flow (CBF) and quantitative histologic microvascular data. Materials and Methods Approval was obtained from the regional review board. ASL data obtained in 129 children between 2011 and 2015 were retrospectively analyzed. CBF and relative CBF in the most perfused area of each neoplasm and contrast enhancement were quantified with a semiquantitative ratio. The correlation between CBF and microvascular density was analyzed in specimens stained with anti-CD34. Results were controlled in two validation cohorts with 1.5- and 3.0-T magnetic resonance (MR) imaging. Results Mean CBF was significantly higher for high-grade than for low-grade hemispheric (116 mL/min/100 g [interquartile range {IQR}, 73-131 mL/min/100 g] vs 29 mL/min/100 g [IQR, 23-35 29 mL/min/100 g], P < .001), thalamic (87 mL/min/100 g [IQR, 73-100 mL/min/100 g] vs 36 mL/min/100 g [IQR, 30-40 mL/min/100 g], P = .016), and posterior fossa (59 mL/min/100 g [IQR, 45-91 mL/min/100 g] vs 33 mL/min/100 g [IQR, 25-40 mL/min/100 g], P < .001) tumors. With a cutoff of 50 mL/min/100 g, sensitivity and specificity were 90% (95% confidence interval [CI]: 68, 100) and 93% (95% CI: 66, 100), respectively, for hemispheric tumors; 100% (95% CI: 48, 100) and 80% (95% CI: 28, 100), respectively, for thalamic tumors; and 65% (95% CI: 51, 78) and 94% (95% CI: 80, 99), respectively, for posterior fossa tumors. In posterior fossa tumors, additional use of the CBF-to-contrast enhancement ratio yielded sensitivity and specificity of 96% (95% CI: 87, 100) and 97% (95% CI: 84, 100), respectively. Use of a simple algorithm based on these values yielded an accuracy of 93% (95% CI: 87, 97). Validation sets yielded similar results, with grading accuracy of 88% (95% CI: 62, 98) with 1.5-T MR imaging and 77% (95% CI: 46, 95) with 3.0-T MR imaging. CBF was strongly correlated with microvascular density (R = 0.66, P < .001). Conclusion High-grade pediatric brain tumors display higher CBF than do low-grade tumors, and they may be accurately graded by using these values. CBF is correlated with tumor microvascular density. © RSNA, 2016 Online supplemental material is available for this article.
Published: 2016
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17. Tuning Eye-Gaze Perception by Transitory STS Inhibition

Author: David Grevent, M. Zilbovicius, Yves Samson, Hervé Lemaitre, Sabine Meunier, Elza Rechtman, Traian Popa, Francis Brunelle, Ana Saitovitch, Nathalie Boddaert, Raphael Calmon, Jean-Charles Lamy, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), HAL-UPMC, Gestionnaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (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), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute ( ICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -CHU Pitié-Salpêtrière [APHP], Université Paris-Sud 11 - Faculté de médecine ( UP11 UFR Médecine ), and CHU Pitié-Salpêtrière [APHP]
Subjects: Male, Visual perception, genetic structures, Cognitive Neuroscience, media_common.quotation_subject, Fixation, Ocular, social cognition, STS, 050105 experimental psychology, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, 0302 clinical medicine, Cognition, Social cognition, Perception, eye-gaze perception, medicine, Humans, 0501 psychology and cognitive sciences, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Eye Movement Measurements, media_common, 05 social sciences, Neural Inhibition, Superior temporal sulcus, Articles, medicine.disease, Gaze, Magnetic Resonance Imaging, Transcranial Magnetic Stimulation, Temporal Lobe, eye diseases, Social Perception, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], TMS, Visual Perception, Autism, Eye tracking, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], sense organs, Psychology, Neuroscience, 030217 neurology & neurosurgery, Cognitive psychology
Abstract: International audience; Processing eye-gaze information is a key step to human social interaction. Neuroimaging studies have shown that superior temporal sulcus (STS) is highly implicated in eye-gaze perception. In autism, a lack of preference for the eyes, as well as anatomo-functional abnormalities within the STS, has been described. To date, there are no experimental data in humans showing whether it is possible to interfere with eye-gaze processing by modulating STS neural activity. Here, we measured eye-gaze perception before and after inhibitory transcranial magnetic stimulation (TMS) applied over the posterior STS (pSTS) in young healthy volunteers. Eye-gaze processing, namely overt orienting toward the eyes, was measured using eye tracking during passive visualization of social movies. Inhibition of the right pSTS led participants to look less to the eyes of characters during visualization of social movies. Such effect was specific for the eyes and was not observed after inhibition of the left pSTS nor after placebo TMS. These results indicate for the first time that interfering with the right pSTS neural activity transitorily disrupts the behavior of orienting toward the eyes and thus indirectly gaze perception, a fundamental process for human social cognition. These results could open up new perspectives in therapeutic interventions in autism.
Published: 2016
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18. Symptomatic Management of Fever in Children: A National Survey of Healthcare Professionals’ Practices in France

Author: Nathalie, Bertille, Gerard, Pons, Babak, Khoshnood, Elisabeth, Fournier-Charrière, Martin, Chalumeau, Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epilepsies de l'Enfant et Plasticité Cérébrale (U1129), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pharmacologie, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Saint-Vincent de Paul-Université Paris Descartes - Paris 5 (UPD5), Centre anti douleur [Bicêtre], Service de Pédiatrie Générale, Assistance Publique - Hôpitaux de Paris, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], CHU Cochin [AP-HP]-Hôpital Saint-Vincent de Paul-Université Paris Descartes - Paris 5 (UPD5), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), HAL-UPMC, Gestionnaire, Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Epilepsies de l'Enfant et Plasticité Cérébrale ( U1129 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and CHU Cochin [AP-HP]-Hôpital Saint-Vincent de Paul-Université Paris Descartes - Paris 5 ( UPD5 )
Subjects: Male, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Fever, Health Personnel, lcsh:R, [ SDV.MHEP.PED ] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Disease Management, Infant, [ SDV.SP.PHARMA ] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, lcsh:Medicine, Professional Practice, Cross-Sectional Studies, Logistic Models, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Child, Preschool, Surveys and Questionnaires, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Humans, Female, lcsh:Q, France, Child, lcsh:Science, Research Article
Abstract: International audience; Despite the production and dissemination of recommendations related to managing fever in children, this symptom saturates the practices of primary healthcare professionals (HPs). Data on parent practices related to fever are available, but data on HPs' practices are limited. We studied HPs' practices, determinants of practices and concordance with recommendations in France. We conducted a national cross-sectional observational study between 2007 and 2008 among French general practitioners, primary care pediatricians and pharmacists. HPs were asked to include 5 consecutive patients aged 1 month to 12 years with acute fever. HPs completed a questionnaire about their practices for the current fever episode. We used a multilevel logistic regression model to assess the joint effects of patient-and HP-level variables associated with this behavior. In all, 1,534 HPs (participation rate 13%) included 6,596 children (mean age 3.7 ± 2.7 years). Physicians measured the temperature of 40% of children. Primary HPs recommended drug treatment for 84% of children (including monotherapy for 92%) and physical treatment for 62% (including all recommended physical treatments for 7%). HPs gave written advice or a pamphlet for 13% of children. Significant practice variations were associated with characteristics of the child (age, fever level and diagnosis) and HP (profession and experience). In France, despite the production and dissemination of national recommendations for managing fever in children, primary HPs' observed practices differed greatly from current recommendations, which suggests potential targets for continuing medical education.
Published: 2015
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19. Effect of clinical spectrum, inoculum size and physician characteristics on sensitivity of a rapid antigen detection test for group A streptococcal pharyngitis

Author: Philippe Bidet, Edouard Bingen, Martin Chalumeau, M. Koskas, Robert M. Cohen, M. Benani, Jérémie F. Cohen, Corinne Levy, Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants (UMR_S 953), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Association Clinique et Thérapeutique du Val-de-Marne (ACTIV), ACTIV, Centre de Recherche Clinique [Créteil] (CRC), Centre Hospitalier Intercommunal de Créteil (CHIC), AP-HP Hôpital universitaire Robert-Debré [Paris], Service de microbiologie, CHI Créteil, This study was internally funded by ACTIV and externally by Dectrapharm, manufacturer of the RADT (Rapid Antigen Detection Test). JFC was supported by educational grants from Agence Régionale de Santé d'Ile-de-France, Laboratoires Guigoz - Société Française de Pédiatrie - Groupe de Pédiatrie Générale - Groupe de Recherches Epidémiologiques en Pédiatrie, and a research grant from the French Ministry of Health (PHRC Régional 2012, AOR 12089)., Debs, Nayla, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants ( UMR_S 953 ), Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche Clinique (CRC), and Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 )
Subjects: Male, Pediatrics, MESH : Streptococcal Infections, MESH : Child, Preschool, medicine.disease_cause, Group A, 0302 clinical medicine, Medical microbiology, MESH : Child, MESH: Streptococcal Infections, Surveys and Questionnaires, MESH: Child, MESH: Physicians, MESH : Female, 030212 general & internal medicine, Child, MESH: Middle Aged, medicine.diagnostic_test, Streptococcus, MESH : Antigens, Bacterial, MESH : Questionnaires, Pharyngitis, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, General Medicine, Middle Aged, 3. Good health, Infectious Diseases, medicine.anatomical_structure, Child, Preschool, MESH : Streptococcus pyogenes, MESH: Immunologic Tests, Female, Clinical Competence, MESH: Clinical Competence, MESH : Sensitivity and Specificity, medicine.symptom, MESH: Streptococcus pyogenes, Microbiology (medical), medicine.medical_specialty, Adolescent, Streptococcus pyogenes, MESH : Male, MESH : Physicians, Immunologic Tests, Sensitivity and Specificity, Asymptomatic, Throat culture, 03 medical and health sciences, Physicians, Streptococcal Infections, MESH : Adolescent, 030225 pediatrics, Throat, medicine, Humans, MESH : Middle Aged, MESH: Adolescent, Antigens, Bacterial, MESH: Humans, business.industry, MESH: Pharyngitis, MESH: Questionnaires, MESH : Pharyngitis, MESH : Humans, MESH: Child, Preschool, MESH : Clinical Competence, Confidence interval, MESH: Sensitivity and Specificity, MESH: Male, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH : Immunologic Tests, MESH: Female, MESH: Antigens, Bacterial
Abstract: International audience; We aimed to assess the independent effect of clinical spectrum, bacterial inoculum size and physician characteristics on the sensitivity of a rapid antigen detection test (RADT) for group A streptococcus (GAS) in children. Double throat swabs were collected from 1,482 children with pharyngitis and 294 asymptomatic children in a French prospective, office-based, multicenter (n = 17) study, from October 2009 to May 2011. Patient- and physician-level factors potentially affecting RADT sensitivity were studied by univariate and multivariate multilevel analysis, with laboratory throat culture as the reference test. In children with pharyngitis and asymptomatic children, the prevalence of GAS was 38 % (95 % confidence interval 36-41 %) and 11 % (7-14 %), respectively. Overall, RADT sensitivity was 87 % (84-90 %). On stratified and multivariate multilevel analysis, RADT sensitivity was higher for children with pharyngitis than asymptomatic children (89 % vs. 41 %), children 99 %). The sensitivity of the RADT is independently affected by patient- and physician-level factors. Physicians who base their diagnosis of GAS pharyngitis on the results of a RADT alone should consider diagnostic accuracy monitoring and adequate training when needed.
Published: 2013
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20. Long time to diagnosis of medulloblastoma in children is not associated with decreased survival or with worse neurological outcome

Author: Stéphanie Puget, Nozar Aghakhani, François Doz, Dominique Valteau-Couanet, Brigitte Lacour, Olivier Delalande, Stephan Gaillard, Martin Chalumeau, Jacques Grill, Jean-François Brasme, Département de Pédiatrie, Institut Gustave Roussy ( IGR ), Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants ( UMR_S 953 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris-Sud - Paris 11 ( UP11 ), Département d'oncologie pédiatrique, INSTITUT CURIE, Registre National des Tumeurs Solides de l'Enfant ( RNTSE ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ) -Cancéropôle du Grand Est, Service de neurochirurgie, Hôpital Foch [Suresnes], Service de neurochirurgie pédiatrique, Fondation Rothschild, Service de neurochirurgie [Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Service de neurochirurgie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de pédiatrie générale [CHU Necker], Institut Gustave Roussy (IGR), Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants (UMR_S 953), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Registre National des Tumeurs Solides de l'Enfant (RNTSE), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Cancéropôle du Grand Est, Fondation Ophtalmologique Adolphe de Rothschild [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Sud - Paris 11 (UP11), and Debs, Nayla
Subjects: Pediatrics, Delayed Diagnosis, Multivariate analysis, Epidemiology, Kaplan-Meier Estimate, 0302 clinical medicine, Interquartile range, Child, Intelligence Tests, education.field_of_study, Univariate analysis, Multidisciplinary, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Tumor Burden, 3. Good health, Treatment Outcome, Oncology, Child, Preschool, 030220 oncology & carcinogenesis, Medicine, Research Article, Cohort study, medicine.medical_specialty, Science, Population, 03 medical and health sciences, Cancer Detection and Diagnosis, medicine, Humans, Cerebellar Neoplasms, education, Proportional Hazards Models, Retrospective Studies, Medulloblastoma, Proportional hazards model, business.industry, Malpractice, Cancers and Neoplasms, Retrospective cohort study, medicine.disease, Surgery, Logistic Models, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Multivariate Analysis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, 030217 neurology & neurosurgery
Abstract: BackgroundThe long time to diagnosis of medulloblastoma, one of the most frequent brain tumors in children, is the source of painful remorse and sometimes lawsuits. We analyzed its consequences for tumor stage, survival, and sequelae.Patients and methodsThis retrospective population-based cohort study included all cases of pediatric medulloblastoma from a region of France between 1990 and 2005. We collected the demographic, clinical, and tumor data and analyzed the relations between the interval from symptom onset until diagnosis, initial disease stage, survival, and neuropsychological and neurological outcome.ResultsThe median interval from symptom onset until diagnosis for the 166 cases was 65 days (interquartile range 31-121, range 3-457). A long interval (defined as longer than the median) was associated with a lower frequency of metastasis in the univariate and multivariate analyses and with a larger tumor volume, desmoplastic histology, and longer survival in the univariate analysis, but not after adjustment for confounding factors. The time to diagnosis was significantly associated with IQ score among survivors. No significant relation was found between the time to diagnosis and neurological disability. In the 62 patients with metastases, a long prediagnosis interval was associated with a higher T stage, infiltration of the fourth ventricle floor, and incomplete surgical resection; it nonetheless did not influence survival significantly in this subgroup.ConclusionsWe found complex and often inverse relations between time to diagnosis of medulloblastoma in children and initial severity factors, survival, and neuropsychological and neurological outcome. This interval appears due more to the nature of the tumor and its progression than to parental or medical factors. These conclusions should be taken into account in the information provided to parents and in expert assessments produced for malpractice claims.
Published: 2012
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21. Adherence to preventive measures after splenectomy in the hospital setting and in the community

Author: Felipe Suarez, Anne Berger, Dominique Salmon, Marianne de Montalembert, Fanny Lanternier, Odile Launay, Olivier Lortholary, Arnaud Hot, Hélène Coignard-Biehler, Marc Lecuit, Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Université Paris Descartes - Paris 5 (UPD5), Hôpital Cochin [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), Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], CHU Necker - Enfants Malades [AP-HP], Service des Maladies infectieuses et tropicales [CHU Necker], Institut Pasteur [Paris], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], and Institut Pasteur [Paris] (IP)
Subjects: Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Hospitals, University, 0302 clinical medicine, Postoperative Complications, MESH: Practice Guidelines as Topic, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Postoperative Complications, MESH: Child, 030212 general & internal medicine, Young adult, Antibiotic prophylaxis, Child, education.field_of_study, MESH: Middle Aged, MESH: Physicians, Primary Care, Incidence (epidemiology), lcsh:Public aspects of medicine, MESH: Paris, Vaccination, General Medicine, Bacterial Infections, Middle Aged, 3. Good health, Anti-Bacterial Agents, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Young Adult, 030220 oncology & carcinogenesis, MESH: Guideline Adherence, Bacterial Vaccines, Practice Guidelines as Topic, Splenectomy, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Guideline Adherence, Infection, Adult, medicine.medical_specialty, Paris, Adolescent, MESH: Bacterial Infections, Population, Meningococcal vaccine, MESH: Splenectomy, Physicians, Primary Care, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Young Adult, MESH: Anti-Bacterial Agents, MESH: Antibiotic Prophylaxis, medicine, Humans, lcsh:RC109-216, Intensive care medicine, education, MESH: Adolescent, MESH: Hospitals, University, MESH: Humans, business.industry, Prevention, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, MESH: Adult, MESH: Vaccination, Antibiotic Prophylaxis, MESH: Male, Pneumococcal vaccine, Emergency medicine, Immunization, business, MESH: Female, MESH: Bacterial Vaccines, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Summary: Overwhelming post-splenectomy infection (OPSI) remains a long-term risk in asplenic patients, which may be reduced by appropriate preventive measures. Specific guidelines have been developed to lower its incidence. Aims: To assess the implementation of guidelines by specialized physicians of a university hospital and primary care physicians. Methods: A retrospective review of splenectomized patients’ medical files over a six year period was carried out. Patients’ general practitioners were contacted and a questionnaire was sent to them. Results: 154 individuals who underwent splenectomy between 2000 and 2005 were eligible (62 children and 92 adults): 70.8% received pneumococcal vaccine, 44% received vaccine against Haemophilus influenzae type b with a good cover of children population (88.7%), 24% received meningococcal vaccine. Prophylactic antibiotics were prescribed in 74% of patients. Septic events were found in 8.4%, and global mortality was 11.7% during a mean follow-up period of 4.5 years. Conclusions: Management of the infectious risk in asplenic patient has to be improved: some of the patients are not correctly identified as at risk of OPSI, and vaccination against Neisseria meningitidis is insufficient. Hospital specialists should improve the implementation of guidelines and give better information to general practitioners involved. Keywords: Prevention, Infection, Splenectomy, Immunization
Published: 2010
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22. A micro-bead device to explore Plasmodium falciparum-infected, spherocytic or aged red blood cells prone to mechanical retention by spleen endothelial slits

Author: François Lacoste, Narla Mohandas, François Paye, Innocent Safeukui, Micheline Guillotte, Sylvie Perrot, Marc Thellier, Corinne Guitton, Alain Sauvanet, Geneviève Milon, Valentine Brousse, Guillaume Deplaine, Anne Couvelard, Pierre Buffet, Dominique Mazier, Odile Puijalon, Fakhri Jeddi, Sylvestre Biligui, Safi Dokmak, Béatrice Aussilhou, Peter H. David, Immunologie moléculaire des parasites, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Immunité et Infection, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR113-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Fond Ackermann, Fondation de France, Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Service d'hématologie, immunologie biologiques et cytogénétique, Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Service de chirurgie hepato-pancreato-biliaire, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Service d'Anatomo-Pathologie, Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Immunophysiologie et Parasitisme Intracellulaire, Institut Pasteur [Paris], New York Blood Centre, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR113-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), New York Blood Center, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-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), CHU Saint-Antoine [AP-HP], Institut Pasteur [Paris] (IP), Service de Parasitologie - Mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and BMC, Ed.
Subjects: Pathology, medicine.medical_specialty, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, health care facilities, manpower, and services, education, 030231 tropical medicine, Population, Spleen, Hereditary spherocytosis, lcsh:Infectious and parasitic diseases, Blood cell, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, lcsh:RC109-216, 030212 general & internal medicine, health care economics and organizations, education.field_of_study, biology, hemic and immune systems, Plasmodium falciparum, medicine.disease, biology.organism_classification, Molecular biology, Hemolysis, stomatognathic diseases, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine.anatomical_structure, Infectious Diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Oral Presentation, Parasitology, circulatory and respiratory physiology
Abstract: Experimental tools to identify human red blood cells (RBC) prone to mechanical retention upstream from the spleen venous sinus inter-endothelial slits are currently suboptimal. We designed a micro-bead device mimicking the geometry of the human narrow and short inter-endothelial slits. Upon filtration through a mixture of 5-25 μm diameter micro-beads, Plasmodium falciparum-hosting RBC (Pf-RBC) were retained in a parasite developmental stage-dependent way, the retention rates of a subset of ring-RBC being similar in micro-beads and in isolated-perfused human spleens. We found that this retention might be linked principally to the reduced surface-area-to-volume ratio of Pf-RBC. Interestingly, other rigid RBC, such as heat-treated RBC, and RBC from hereditary spherocytosis patients were also retained in micro-beads without any hemolysis. Micro-beads allow (i) depletion of heterogeneous RBC population from its rigid-RBC subpopulation ii) characteriziation of distinct molecular signatures of rigid versus deformable RBC subpopulations. This simple method portends wide medical applications, such as improving the quality of stored RBC concentrates prior to transfusion.
Published: 2010
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23. Effectiveness of chest physiotherapy in infants hospitalized with acute bronchiolitis: a multicenter, randomized, controlled trial

Author: Véronique Abadie, Nicole Beydon, Sylvie Chevret, Jean Bouyer, Philippe Labrune, Loïc de Pontual, Sophie Larrar, Alix Mollet-Boudjemline, Sandrine Katsahian, Vincent Gajdos, Sylvain Bailleux, Bertrand Chevallier, Ralph Epaud, Service de pédiatrie [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biostatistiques et information médicale [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pneumologie [Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de Pédiatrie [Jean Verdier], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Service d'urgences pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pédiatrie, urgences enfants [CHU Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], This work was supported by a grant from French Health Ministry (PHRC AOM 03/123) and by a grant from the Association des Réseaux Bronchiolites (ARB)., Autard, Delphine, AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Antoine Béclère, Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris 13 ( UP13 ) -Hôpital Jean Verdier, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de pédiatrie, urgences enfants, and Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré
Subjects: Pediatrics, MESH: Bronchiolitis, MESH: Hospitalization, Respiratory Medicine/Respiratory Infections, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, 0302 clinical medicine, Randomized controlled trial, law, 030212 general & internal medicine, MESH: Treatment Outcome, First episode, Human studies, MESH: Respiratory Therapy, MESH : Infant, General Medicine, MESH : Bronchiolitis, MESH: Infant, 3. Good health, Hospitalization, Treatment Outcome, Acute Bronchiolitis, MESH : Hospitalization, Medicine, Bronchiolitis, France, Research Article, Respiratory Therapy, medicine.medical_specialty, MESH : Respiratory Therapy, MESH : Treatment Outcome, Chest physiotherapy, Pediatrics and Child Health/Respiratory Pediatrics, 03 medical and health sciences, 030225 pediatrics, Infectious Diseases/Viral Infections, medicine, Humans, MESH : France, MESH: Humans, business.industry, MESH : Humans, Infant, medicine.disease, Clinical trial, MESH: France, Clinical research, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
Abstract: Vincent Gajdos and colleagues report results of a randomized trial conducted among hospitalized infants with bronchiolitis. They show that a physiotherapy technique (increased exhalation and assisted cough) commonly used in France does not reduce time to recovery in this population., Background Acute bronchiolitis treatment in children and infants is largely supportive, but chest physiotherapy is routinely performed in some countries. In France, national guidelines recommend a specific type of physiotherapy combining the increased exhalation technique (IET) and assisted cough (AC). Our objective was to evaluate the efficacy of chest physiotherapy (IET + AC) in previously healthy infants hospitalized for a first episode of acute bronchiolitis. Methods and Findings We conducted a multicenter, randomized, outcome assessor-blind and parent-blind trial in seven French pediatric departments. We recruited 496 infants hospitalized for first-episode acute bronchiolitis between October 2004 and January 2008. Patients were randomly allocated to receive from physiotherapists three times a day, either IET + AC (intervention group, n = 246) or nasal suction (NS, control group, n = 250). Only physiotherapists were aware of the allocation group of the infant. The primary outcome was time to recovery, defined as 8 hours without oxygen supplementation associated with minimal or no chest recession, and ingesting more than two-thirds of daily food requirements. Secondary outcomes were intensive care unit admissions, artificial ventilation, antibiotic treatment, description of side effects during procedures, and parental perception of comfort. Statistical analysis was performed on an intent-to-treat basis. Median time to recovery was 2.31 days, (95% confidence interval [CI] 1.97–2.73) for the control group and 2.02 days (95% CI 1.96–2.34) for the intervention group, indicating no significant effect of physiotherapy (hazard ratio [HR] = 1.09, 95% CI 0.91–1.31, p = 0.33). No treatment by age interaction was found (p = 0.97). Frequency of vomiting and transient respiratory destabilization was higher in the IET + AC group during the procedure (relative risk [RR] = 10.2, 95% CI 1.3–78.8, p = 0.005 and RR = 5.4, 95% CI 1.6–18.4, p = 0.002, respectively). No difference between groups in bradycardia with or without desaturation (RR = 1.0, 95% CI 0.2–5.0, p = 1.00 and RR = 3.6, 95% CI 0.7–16.9, p = 0.10, respectively) was found during the procedure. Parents reported that the procedure was more arduous in the group treated with IET (mean difference = 0.88, 95% CI 0.33–1.44, p = 0.002), whereas there was no difference regarding the assessment of the child's comfort between both groups (mean difference = −0.07, 95% CI −0.53 to 0.38, p = 0.40). No evidence of differences between groups in intensive care admission (RR = 0.7, 95% CI 0.3–1.8, p = 0.62), ventilatory support (RR = 2.5, 95% CI 0.5–13.0, p = 0.29), and antibiotic treatment (RR = 1.0, 95% CI 0.7–1.3, p = 1.00) was observed. Conclusions IET + AC had no significant effect on time to recovery in this group of hospitalized infants with bronchiolitis. Additional studies are required to explore the effect of chest physiotherapy on ambulatory populations and for infants without a history of atopy. Trial registration ClinicalTrials.gov NCT00125450 Please see later in the article for the Editors' Summary, Editors' Summary Background Bronchiolitis, which is usually caused by the respiratory syncytial virus (RSV), is the commonest infection of the lower respiratory tract (the lungs and the passages through which air enters the lungs) in infants. A third of all children have bronchiolitis during their first year of life. The illness begins with stuffiness, a runny nose, a mild cough, and mild fever. Then, as the smallest airways in the lung (the bronchioles) become inflamed (swell) and blocked with mucus, the cough worsens, and the infant may develop a wheeze, shallow breathing, and a rapid heartbeat. Most cases of bronchiolitis are mild and clear up within two weeks without any treatment but some infants develop severe disease. Such infants struggle to get enough air into their lungs, drawing in their chest with each breath (chest recession). They have trouble eating and drinking, and the oxygen level in their blood can drop dangerously low. About 1% of previously healthy infants need hospitalization because of severe bronchiolitis. These severely affected infants are not normally given any medications but, where necessary, they are given oxygen therapy, fed through a tube into their stomach, and given fluids through a vein. Why Was This Study Done? In some countries, chest physiotherapy is routinely given to infants with bronchiolitis even though this is not a recommended treatment internationally. In France, for example, virtually all outpatients with bronchiolitis receive a form of chest physiotherapy known as increased exhalation technique with assisted cough (IET + AC). IET—manual chest compression—is designed to clear mucus from the bronchioles whereas AC—coughing triggered by applying pressure to the top of the breastbone—facilitates clearance of the large airways. But is IET + AC an effective treatment for bronchiolitis? In this study, the researchers undertook a multicenter, randomized, controlled trial to answer this question. A randomized trial is a study in which patients are randomly allocated to receive either the treatment under study or a control treatment. Usually in such trials, noone is aware of the treatment allocations until the trial has been completed. This is called blinding and avoids unconscious biases being introduced into the results. In this trial, although the parents, caregivers, and outcome assessors were blinded, the physiotherapists and the infants were aware of treatment allocations. The physiotherapists were not involved in patient assessment, however, and the infants were sufficiently young that their knowledge of their treatment was unlikely to bias the results. What Did the Researchers Do and Find? The researchers enrolled nearly 500 children aged 15 days to 2 years who were admitted to seven French hospitals for a first episode of acute bronchiolitis. They randomly allocated the patients to receive IET + AC (intervention group) or nasal suction (control group) three times a day from a physiotherapist working alone in a room with blacked-out windows. The primary outcome of the trial was the patients' time to recovery. Infants were judged to have recovered if they had not had oxygen therapy or showed signs of chest recession for 8 hours and had ingested more than two-thirds of their daily food requirement. Infants in the control group took an average of 2.31 days to recover whereas those in the intervention group took 2.02 days. However, this difference in recovery time was not statistically significant. That is, it could have happened by chance. The researchers also recorded several secondary outcomes such as admission to an intensive care unit, help with breathing, antibiotic treatment, and parental perceptions of their child's comfort. There were no significant differences between the two treatment groups for any of these secondary outcomes, although the parents did report that the IET + AC treatment was harder on their children than nasal suction while not reducing their overall comfort. What Do These Findings Mean? These findings show that IET + AC had no significant effect on the time to recovery of a large population of French infants admitted to hospital with severe bronchiolitis. These results cannot be extrapolated, however, to infants with mild or moderate bronchiolitis, and further studies are needed to assess whether chest physiotherapy is of any benefit in an outpatient setting. Three small trials of a different form of chest physiotherapy have also previously failed to find any effect of chest physiotherapy on recovery time. Thus, none of the currently available results support the routine use of chest physiotherapy in infants admitted to a hospital for severe bronchiolitis. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000345 The UK National Health Service Choices Web site provides detailed information on all aspects of bronchiolitis Kidshealth, a resource maintained by the Nemours Foundation (a not-for-profit organization for children's health) provides information for parents on bronchiolitis schizophrenia and on respiratory syncytial virus (in English and Spanish) The British Lung Foundation also provides information on bronchiolitis schizophrenia and on respiratory syncytial virus The MedlinePlus encyclopedia has a page on bronchiolitis schizophrenia (in English and Spanish) The US Centers for Disease Control and Prevention has detailed information on respiratory syncytial virus
Published: 2010
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24. CC2D2A mutations in Meckel and Joubert syndromes indicate a genotype-phenotype correlation

Author: Ali Saad, Raymonde Bouvier, S. Romano, Nadia Elkhartoufi, Sophie Audollent, Anne Lise Delezoide, Sophie Saunier, Tania Attié-Bitach, Sophie Patrier, Nathalie Boddaert, Candice Babarit, Rémi Salomon, Jelena Martinovic, Marie Pierre Cordier, Enza Maria Valente, Chantal Esculpavit, Emmanuelle Szenker, Estelle Escudier, Soumaya Mougou-Zerelli, Marie Claire Gubler, Marie Gonzales, Michel Vekemans, Férechté Encha-Razavi, Arnold Munnich, Jeanne Amiel, Joelle Roume, Sylvie Odent, Philippe Loget, Marion Gérard, B. Leheup, Suonavy Khung, Sophie Thomas, Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Cytogénétique, Génétique moléculaire et Biologie de la reproduction, Hôpital Farhat Hached, Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pédiatrie générale [CHU Necker], Neuropathies héréditaires et rein en développement, Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Physiopathologie des maladies génétiques d'expression pédiatrique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine Infantile III et Génétique Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Cabinet d'Anatomie et Cytologie Pathologiques Richier, Service de génétique clinique [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, Service de génétique médicale, CHI Poissy-Saint-Germain, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service de Biologie du Développement, Service de Génétique, Hospices Civils de Lyon (HCL), Centre de pathologie Est, Service de radiologie pédiatrique [CHU Necker], Imagerie Cerebrale en Psychiatrie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Istituto CSS Mendel [Rome, Italy], Department of Medical and Surgical Pediatrics, University Hospital, Messina, French National Research Agency (ANR) : ANR-06-MRAR-034-02United States Department of Health & Human Services National Institutes of Health (NIH) - USA : NS039818-07Fondazione Telethon : GGP08145INSERM-Direction generale de la recherche scientifique et de la renovation technologique (DGRSRT) : CS/RN/2008 56, CS/RN/2008 87, Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de génétique et embryologie médicales [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Service de génétique clinique, Hôpital Sud, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), Hospices Civils de Lyon ( HCL ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Istituto CSS Mendel, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), De Villemeur, Hervé, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), and hôpital Sud
Subjects: Male, TMEM67, MESH : Genotype, [SDV.GEN] Life Sciences [q-bio]/Genetics, Ciliopathies, MESH : Syndrome, Cohort Studies, MESH : Proteins, MESH: Genotype, 0302 clinical medicine, MESH: Gene Expression Regulation, Developmental, Missense mutation, Developmental, MESH: Syndrome, MESH: Proteins, MESH: Cohort Studies, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Genetics (clinical), In Situ Hybridization, MESH: Genetic Association Studies, Genetics, 0303 health sciences, Polydactyly, Gene Expression Regulation, Developmental, MESH : In Situ Hybridization, Syndrome, 3. Good health, MESH : Phenotype, Phenotype, RPGRIP1L, MESH : RNA Splicing, MESH : Mutation, MESH: Mutation, Genotype, RNA Splicing, MESH : Male, MESH : Cohort Studies, Genes, Recessive, Biology, CC2D2A, MESH: Phenotype, MESH: Nervous System Diseases, Article, Joubert syndrome, 03 medical and health sciences, MESH: In Situ Hybridization, [SDV.BDD] Life Sciences [q-bio]/Development Biology, medicine, Alleles, Gene Expression Regulation, Genes, Recessive, Genetic Association Studies, Humans, Mutation, Nervous System Diseases, Proteins, [ SDV.BDD ] Life Sciences [q-bio]/Development Biology, MESH: Genes, Recessive, 030304 developmental biology, Meckel-Gruber Syndrome, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, urogenital system, MESH: Alleles, MESH : Humans, MESH : Genes, Recessive, MESH : Nervous System Diseases, MESH : Genetic Association Studies, medicine.disease, MESH: Male, Cytoskeletal Proteins, MESH : Gene Expression Regulation, Developmental, MESH : Alleles, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, MESH: RNA Splicing, 030217 neurology & neurosurgery
Abstract: International audience; Meckel-Gruber syndrome (MKS) is a lethal fetal disorder characterized by diffuse renal cystic dysplasia, polydactyly, a brain malformation that is usually occipital encephalocele, and/or vermian agenesis, with intrahepatic biliary duct proliferation. Joubert syndrome (JBS) is a viable neurological disorder with a characteristic "molar tooth sign" (MTS) on axial images reflecting cerebellar vermian hypoplasia/dysplasia. Both conditions are classified as ciliopathies with an autosomal recessive mode of inheritance. Allelism of MKS and JBS has been reported for TMEM67/MKS3, CEP290/MKS4, and RPGRIP1L/MKS5. Recently, one homozygous splice mutation with a founder effect was reported in the CC2D2A gene in Finnish fetuses with MKS, defining the 6th locus for MKS. Shortly thereafter, CC2D2A mutations were also reported in JBS. The analysis of the CC2D2A gene in our series of MKS fetuses, identified 14 novel truncating mutations in 11 cases. These results confirm the involvement of CC2D2A in MKS and reveal a major contribution of CC2D2A to the disease. We also identified three missense CC2D2A mutations in two JBS cases. Therefore, and in accordance with the data reported regarding RPGRIP1L, our results indicate phenotype-genotype correlations, as missense and presumably hypomorphic mutations lead to JBS while all null alleles lead to MKS.
Published: 2009
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25. Genetic testing to provide targeted treatment for cystic fibrosis patients

Author: Isabelle Sermet-Gaudelus, Jean-Pierre Rousset, Aleksander Edelman, Régulation des systèmes de transport dans les épithéliums (UMR_S467), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Necker - Enfants Malades [AP-HP], Institut de recherches sur la catalyse (IRC), Centre National de la Recherche Scientifique (CNRS), Laboratoire de mécanique des fluides (LMF), École Centrale de Nantes (ECN) - Centre National de la Recherche Scientifique (CNRS), Institut de génétique et microbiologie [Orsay] (IGM), Université Paris-Sud - Paris 11 (UP11) - Centre National de la Recherche Scientifique (CNRS), Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon - Université de Lyon - Centre National de la Recherche Scientifique (CNRS), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cystic Fibrosis, media_common.quotation_subject, Nonsense, Cystic Fibrosis Transmembrane Conductance Regulator, Genetic Counseling, Cystic fibrosis, Rene descartes, 03 medical and health sciences, 0302 clinical medicine, Genetics, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, Genetic Predisposition to Disease, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetic Testing, 030304 developmental biology, Genetic testing, media_common, Pharmacology, 0303 health sciences, medicine.diagnostic_test, Philosophy, Genetic Therapy, Peptide Chain Termination, Translational, medicine.disease, 3. Good health, 030220 oncology & carcinogenesis, Molecular Medicine, Humanities
Abstract: Aleksander Edelman1,2†, Isabelle Sermet-Gaudelus2,3 & Jean-Pierre Rousset4,5 †Author for correspondence 1INSERM, U845, Paris, France E-mail: edelman@necker.fr 2Universite Paris-Descartes, Faculte de Medecine Rene Descartes, Paris, France 3Centre de Ressources et de Competance en Mucoviscidose, Hopital Necker-Enfants Malades, AP-HP, Paris, France 4IGM, University Paris-Sud, UMR 8621, Orsay, F 91405, France 5CNRS, Orsay, F 91405, France ‘Experimental data suggests that in the next decade, genetic testing will become a useful and necessary approach to treat cystic fibrosis and other diseases caused by nonsense mutations.’
Published: 2007
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26. The CF-CIRC study: a French collaborative study to assess the accuracy of Cystic Fibrosis diagnosis in neonatal screening

Author: Aleksander Edelman, Philippe Reix, Stéphanie Bui, E. Deneuville, F. Huet, Gérard Lenoir, Delphine Roussel, Gabriel Bellon, Isabelle Sermet-Gaudelus, Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Régulation des systèmes de transport dans les épithéliums (UMR_S467), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Ressources et de Compétences en Mucoviscidose [CHU Toulouse] (CRCM Toulouse), Service Pneumologie et allergologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Ressources et de Compétences de la Mucoviscidose, hôpital Sud, Hôpital d'Enfants du Bocage, Centre de Ressources et de compétences de la mucoviscidose (CRCM), Hôpital Debrousse, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Supported by Assistance Publique des Hôpitaux de Paris, Vaincre La Mucoviscidose and ABCF Protéines Associations., Edelman, Aleksander, Centre de Ressources et de Compétences de la Mucoviscidose (CRCM), Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Sud, and Hospices Civils de Lyon (HCL) - Hospices Civils de Lyon (HCL)
Subjects: Male, Pathology, Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator, Mucous membrane of nose, MESH : Equipment Design, MESH : Child, Preschool, MESH: Catheterization, medicine.disease_cause, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Cystic fibrosis, Gastroenterology, MESH: Amiloride, Amiloride, Study Protocol, MESH : Catheterization, MESH: Genetic Screening, Subcutaneous Tissue, 0302 clinical medicine, MESH : Electric Conductivity, Reference Values, MESH : Chlorides, MESH : Female, 030212 general & internal medicine, Sympathomimetics, Sweat, MESH: Cystic Fibrosis Transmembrane Conductance Regulator, Mutation, biology, medicine.diagnostic_test, lcsh:RJ1-570, MESH : Infant, Equipment Design, MESH: Infant, Cystic fibrosis transmembrane conductance regulator, Electrodes, Implanted, 3. Good health, Perfusion, Research Design, Child, Preschool, Chloride channel, Female, France, Sodium Channel Blockers, MESH: Infant, Newbo, medicine.medical_specialty, MESH : Electrodes, Implanted, MESH: Cystic Fibrosis, MESH: Electric Conductivity, Sensitivity and Specificity, Catheterization, 03 medical and health sciences, MESH : Amiloride, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Neonatal Screening, Chlorides, Predictive Value of Tests, MESH : Cystic Fibrosis, 030225 pediatrics, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Immunoreactive trypsinogen, Pediatrics, Perinatology, and Child Health, Genetic Testing, MESH: Chlorides, MESH : France, Genetic testing, MESH : Genetic Screening, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Newborn screening, MESH: Humans, Ion Transport, business.industry, MESH : Cystic Fibrosis Transmembrane Conductance Regulator, MESH : Humans, MESH: Child, Preschool, Sodium, Electric Conductivity, Infant, Newborn, Isoproterenol, Infant, lcsh:Pediatrics, medicine.disease, MESH: France, Nasal Mucosa, MESH : Infant, Newbo, Pediatrics, Perinatology and Child Health, biology.protein, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Electrodes, Implanted, business, MESH: Female, MESH: Equipment Design
Abstract: Background Cystic fibrosis (CF) is caused by mutations in the gene encoding for the CF transmembrane conductance regulator (CFTR) protein, which acts as a chloride channel after activation by cyclic AMP (cAMP). Newborn screening programs for CF usually consist of an immunoreactive trypsinogen (IRT) assay, followed when IRT is elevated by testing for a panel of CF-causing mutations. Some children, however, may have persistent hypertrypsinogenemia, only one or no identified CFTR gene mutation, and sweat chloride concentrations close to normal values. In vivo demonstration of abnormal CFTR protein function would be an important diagnostic aid in this situation. Measurements of transepithelial nasal potential differences (NPD) in adults accurately characterize CFTR-related ion transport. The aim of the present study is to establish reference values for NPD measurements for healthy children and those with CF aged 3 months to 3 years, the age range of most difficult-to-diagnose patients with suspected CF. The ultimate goal of our study is to validate NPD testing as a diagnostic tool for children with borderline results in neonatal screening. Methods/Design We adapted the standard NPD protocol for young children, designed a special catheter for them, used a slower perfusion rate, and shortened the protocol to include only measurement of basal PD, transepithelial sodium (Na+) transport in response to the Na+ channel inhibitor amiloride, and CFTR-mediated chloride (Cl-) secretion in response to isoproterenol, a β-agonist in a Cl- free solution. The study will include 20 children with CF and 20 healthy control children. CF children will be included only if they carry 2 CF-causing mutations in the CFTR gene or have sweat chloride concentrations > 60 mEq/L or both. The healthy children will be recruited among the siblings of the CF patients, after verification that they do not carry the familial mutation. Discussion A preliminary study of 3 adult control subjects and 4 children older than 12 years with CF verified that the new protocol was well tolerated and produced NPD measurements that did not differ significantly from those obtained with the standard protocol. This preliminary study will provide a basis for interpreting NPD measurements in patients with suspected CF after neonatal screening. Earlier definitive diagnosis should alleviate parental distress and allow earlier therapeutic intervention and genetic counseling.
Published: 2006
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27. Eosinophil-derived neurotoxin suggests early eosinophil activation may be involved in COVID-19-related immune exhaustion

Author: Abecassis, A., Sereme, Y., Michel, M., Menard, A., Sahli, W., Perrier, R., Mege, J., Philippe Gautret, Vitte, J., Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut Desbrest de santé publique (IDESP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background: Upregulation of PD-L1 (B7-H1, CD274) on eosinophils (Eos) discriminates moderate/severe (MOD) and mild forms of COVID-19. PD-L1 is a ligand of PD-1 (CD279), a coinhibitory receptor (immune checkpoint) expressed by T cells and thus a gatekeeper for broad adaptive immune suppression. Outside COVID-19, PD-L1/PD-1-mediated synapses enable Eos to downregulate T cell responses, mainly in the context of Eos activation and degranulation. We sought to determine Eos activation during COVID-19.Method: Eosinophil-derived neurotoxin (EDN), a granular RNase specific of Eos, was measured with an experimental fluoroimmunoenzyme assay in the serum of 79 COVID-19 patients (PCR-confirmed) at 0–180 days post-symptom onset (PSO) and of 15 PCR-negative controls. Serum (s) EDN, Eos blood counts and the EDN/blood Eos ratio were analyzed as a function of COVID-19 severity and time PSO. Results are expressed as median and interquartile range (IQR).Results: Patients experienced mild (60) or MOD (19) COVID-19. The former received outpatient care. Moderate (MOD) required hospitalization and oxygen but not intensive care. MOD (59.41–71) were older than controls (32.24–54) but not mild (39.26–51). Overall, sEDN levels in mild COVID-19 at any time PSO were lower than in controls or MOD: 49 (25–75), 69 (36–98) and 78 (54–125) µg/L, p < 0.05. sEDN decreased in mild COVID-19 as early as the first 24h PSO, remained significantly lower until day 22, and was still lower, albeit not significantly, after 6 months. Eos counts dropped in MOD (median
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28. Subtotal and total splenectomy for hereditary pyropoikilocytosis: Benefits and outcomes.

Author: Pincez T, Guitton C, Landman-Parker J, Brousse V, Gauthier F, Da Costa L, Ghazal K, Dufillot D, Tchernia G, Picard V, and Garçon L
Subjects: Blood Transfusion, Combined Modality Therapy, Elliptocytosis, Hereditary blood, Elliptocytosis, Hereditary physiopathology, Ferritins blood, Follow-Up Studies, Hemoglobins analysis, Humans, Infant, Organ Size, Platelet Count, Reoperation, Retrospective Studies, Spleen physiopathology, Treatment Outcome, Elliptocytosis, Hereditary surgery, Splenectomy methods
Published: 2018
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28 results on '"Service de pédiatrie générale [CHU Necker]"'

1. Cellules de l’allergie : mise au point sur les mastocytes et les éosinophiles

2. Safety of Cyproheptadine, an Orexigenic Drug. Analysis of the French National Pharmacovigilance Data-Base and Systematic Review

3. Oxidative stress activates red cell adhesion to laminin in sickle cell disease

4. One-Fifth of Children with Sickle Cell Anemia Show Exercise-Induced Hemoglobin Desaturation: Rate of Perceived Exertion and Role of Blood Rheology

5. Functional Vision Analysis in Patients With CHARGE Syndrome

6. Association of Matched-Sibling Donor Hematopoietic Stem Cell Transplantation with Transcranial-Doppler Velocities in Children with Sickle Cell Anemia

7. Prognostic factors of disease severity in infants with sickle cell anemia: A comprehensive longitudinal cohort study

8. Chromosome 14q32.2 Imprinted Region Disruption as an Alternative Molecular Diagnosis of Silver-Russell Syndrome

9. Fulminant Nocardiosis Due to a Multidrug-Resistant Isolate in a 12-Year-Old Immunocompetent Child

10. Supplementary data to: Algorithms to define abnormal growth in children: external validation and head-to-head 3 comparison 4 5

11. A microfluidic approach to study the effect of mechanical stress on erythrocytes in sickle cell disease

12. Design of the DREPAGREFFE trial: A prospective controlled multicenter study evaluating the benefit of genoidentical hematopoietic stem cell transplantation over chronic transfusion in sickle cell anemia children detected to be at risk of stroke by transcranial Doppler (NCT 01340404)

13. Cardiac iron overload in chronically transfused patients with thalassemia, sickle cell anemia, or myelodysplastic syndrome

14. Gene Therapy in a Patient with Sickle Cell Disease

15. A simplified, semi-quantitative structural lung disease computed tomography outcome during quiet breathing in infants with cystic fibrosis

16. Arterial Spin Labeling to Predict Brain Tumor Grading in Children: Correlations between Histopathologic Vascular Density and Perfusion MR Imaging

17. Tuning Eye-Gaze Perception by Transitory STS Inhibition

18. Symptomatic Management of Fever in Children: A National Survey of Healthcare Professionals’ Practices in France

19. Effect of clinical spectrum, inoculum size and physician characteristics on sensitivity of a rapid antigen detection test for group A streptococcal pharyngitis

20. Long time to diagnosis of medulloblastoma in children is not associated with decreased survival or with worse neurological outcome

21. Adherence to preventive measures after splenectomy in the hospital setting and in the community

22. A micro-bead device to explore Plasmodium falciparum-infected, spherocytic or aged red blood cells prone to mechanical retention by spleen endothelial slits

23. Effectiveness of chest physiotherapy in infants hospitalized with acute bronchiolitis: a multicenter, randomized, controlled trial

24. CC2D2A mutations in Meckel and Joubert syndromes indicate a genotype-phenotype correlation

25. Genetic testing to provide targeted treatment for cystic fibrosis patients

26. The CF-CIRC study: a French collaborative study to assess the accuracy of Cystic Fibrosis diagnosis in neonatal screening

27. Eosinophil-derived neurotoxin suggests early eosinophil activation may be involved in COVID-19-related immune exhaustion

28. Subtotal and total splenectomy for hereditary pyropoikilocytosis: Benefits and outcomes.

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