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1. Mesenchymal stem cells increase proliferation but do not change quiescent state of osteosarcoma cells: Potential implications according to the tumor resection status

Author

Philippe Rosset, Pierre Perrot, Pierre Avril, Louis-Romée Le Nail, Dominique Heymann, Pierre Layrolle, Meadhbh Á. Brennan, Gonzague de Pinieux, Valérie Trichet, Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Chirurgie Orthopédique et Traumatologique 2 [CHRU Tours], Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université Francois Rabelais [Tours]-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Chirurgie Plastique et des Brulés [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), This work was supported by INSERM, the 'Ligue Contre le Cancer' (Equipe Labellisée LIGUE 2012, grant EL2012NCC/DH), the 'Fédération Nationale Enfants et Santé' and the 'Société Française de lutte contre les Cancers et les leucémies de l'Enfant et de l'Adolescent('appel à projet 2013')., Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université Francois Rabelais [Tours], and maurice, sandrine

Subjects
0301 basic medicine, musculoskeletal diseases, Pathology, medicine.medical_specialty, lcsh:Diseases of the musculoskeletal system, Osteolysis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell cycle, Quiescence, lcsh:RC254-282, Cell therapy, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Osteoclast, Medicine, Mesenchymal stem cell, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Osteosarcoma, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Oncology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Adipose tissue transfer, 030220 oncology & carcinogenesis, Sarcoma, lcsh:RC925-935, Stem cell, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Paper
Abstract

Conventional therapy of primary bone tumors includes surgical excision with wide resection, which leads to physical and aesthetic defects. For reconstruction of bone and joints, allografts can be supplemented with mesenchymal stem cells (MSCs). Similarly, adipose tissue transfer (ATT) is supplemented with adipose-derived stem cells (ADSCs) to improve the efficient grafting in the correction of soft tissue defects. MSC-like cells may also be used in tumor-targeted cell therapy. However, MSC may have adverse effects on sarcoma development. In the present study, human ADSCs, MSCs and pre-osteoclasts were co-injected with human MNNG-HOS osteosarcoma cells in immunodeficient mice. ADSCs and MSCs, but not the osteoclast precursors, accelerated the local proliferation of MNNG-HOS osteosarcoma cells. However, the osteolysis and the metastasis process were not exacerbated by ADSCs, MSCs, or pre-osteoclasts. In vitro proliferation of MNNG-HOS and Saos-2 osteosarcoma cells was increased up to 2-fold in the presence of ADSC-conditioned medium. In contrast, ADSC-conditioned medium did not change the dormant, quiescent state of osteosarcoma cells cultured in oncospheres. Due to the enhancing effect of ADSCs/MSCs on in vivo/in vitro proliferation of osteosarcoma cells, MSCs may not be good candidates for osteosarcoma-targeted cell therapy. Although conditioned medium of ADSCs accelerated the cell cycle of proliferating osteosarcoma cells, it did not change the quiescent state of dormant osteosarcoma cells, indicating that ADSC-secreted factors may not be involved in the risk of local recurrence., Graphical abstract fx1

Published
2016
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2. Feasibility and safety of treating non-unions in tibia, femur and humerus with autologous, expanded, bone marrow-derived mesenchymal stromal cells associated with biphasic calcium phosphate biomaterials in a multicentric, non-comparative trial

Author

Nicola Baldini, Elena Veronesi, Nathalie Chevallier, Enrique Gómez-Barrena, Philippe Rosset, Pierre Layrolle, Philippe Hernigou, Cristina Avendaño-Solá, Gabriela Ciapetti, Sandrine Fleury, Massimo Dominici, Tiziana Montemurro, Rosaria Giordano, José Cordero-Ampuero, Jose Rafael Cabrera, M.N. Fernández, Hélène Rouard, Juan Carlos Rubio-Suárez, Ramin Lotfi, Markus Rojewski, Christian Ehrnthaller, Luc Sensebé, Hubert Schrezenmeier, Markus Huber-Lang, Florian Gebhard, Charles Henri Flouzat-Lachaniette, Norma G. Padilla-Eguiluz, Julien Stanovici, Davide Maria Donati, Carmen Panaitescu, Rosa Gonzalo-Daganzo, Eduardo García-Rey, Servicio de Cirugía Ortopédica y Traumatología [Madrid, Spain], Universidad Autonoma de Madrid (UAM)-Hospital Universitario La Paz-IdiPAZ and Facultad de Medicina [Madrid, Spain], Service de Chirurgie Orthopédique et Traumatologique 2 [CHU Tours], Hôpital Trousseau (Tours)-Université Francois Rabelais [Tours]-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Department of Traumatology, Hand-, Plastic-, and Reconstructive Surgery [Ulm, Germany], Universität Ulm - Ulm University [Ulm, Allemagne]-Center of Surgery [Ulm, Germany], Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine [Bologna, Italy], University of Bologna-Department of Biomedical and Neuromotor Sciences [Bologna, Italy], Istituto Ortopedico Rizzoli [Bologna, Italy]-Istituto Ortopedico Rizzoli [Bologna, Italy], Etablissement Français du Sang Ile de France (EFS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], STROMALab, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Servicio de Hematología [Madrid, Spain], Universidad Autonoma de Madrid (UAM)-Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain], Cell Factory, Center for Cellular Therapy and Cryobiology [Milano, Italy], Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Victor Babes University of Medicine and Pharmacy [Timisoara, Romania], Laboratory of Cellular Therapies [Modena, Italy], University - Hospital of Modena and Reggio Emilia [Modena, Italy]- Department of Medical and Surgical Sciences for Children & Adults [Modena, Italy], Institute for Clinical Transfusion Medicine and Immunogenetic Ulm [Ulm, Germany], Institut für Klinische Transfusionsmedizin und Immungenetik Ulm -IKT [Ulm, Germany], Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), EU-FP7-HEALTH-2009, REBORNE Project (GA: 241876)., Hospital Universitario La Paz-IdiPAZ and Facultad de Medicina [Madrid, Spain]-Universidad Autonoma de Madrid (UAM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Université Francois Rabelais [Tours]-Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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 National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), Victor Babeş University of Medicine and Pharmacy (UMFT), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), UAM. Departamento de Cirugía, UAM. Departamento de Farmacología, UAM. Departamento de Medicina, Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université Francois Rabelais [Tours]-Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Gómez-Barrena, Enrique, Rosset, Philippe, Gebhard, Florian, Hernigou, Philippe, Baldini, Nicola, Rouard, Helène, Sensebé, Luc, Gonzalo-Daganzo, Rosa M., Giordano, Rosaria, Padilla-Eguiluz, Norma, García-Rey, Eduardo, Cordero-Ampuero, José, Rubio-Suárez, Juan Carlo, Stanovici, Julien, Ehrnthaller, Christian, Huber-Lang, Marku, Flouzat-Lachaniette, Charles Henri, Chevallier, Nathalie, Donati, Davide Maria, Ciapetti, Gabriela, Fleury, Sandrine, Fernandez, Manuel-Nicolá, Cabrera, José-Rafael, Avendaño-Solá, Cristina, Montemurro, Tiziana, Panaitescu, Carmen, Veronesi, Elena, Rojewski, Markus Thoma, Lotfi, Ramin, Dominici, Massimo, Schrezenmeier, Hubert, Layrolle, Pierre, Universidad Autónoma de Madrid (UAM)-Hospital Universitario La Paz-IdiPAZ and Facultad de Medicina [Madrid, Spain], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université Francois Rabelais [Tours], University of Bologna/Università di Bologna-Department of Biomedical and Neuromotor Sciences [Bologna, Italy], Universidad Autónoma de Madrid (UAM)-Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain], Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), and maurice, sandrine

Subjects
Calcium Phosphates, Biocompatible Materials, 02 engineering and technology, Bone tissue engineering, Fractures, Bone, Femur, media_common, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, 021001 nanoscience & nanotechnology, 3. Good health, Clinical trial, medicine.anatomical_structure, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Mechanics of Materials, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 0210 nano-technology, medicine.medical_specialty, Bioceramic, Medicina, Biophysics, Ceramics and Composite, Bioengineering, Mesenchymal Stem Cell Transplantation, Non-union, Transplantation, Autologous, Non union, Expanded autologous BM-hMSC, Biomaterials, 03 medical and health sciences, medicine, media_common.cataloged_instance, Humans, Humerus, Tibia, European union, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, 030304 developmental biology, Cell Proliferation, [SDV.IB] Life Sciences [q-bio]/Bioengineering, business.industry, Mesenchymal stem cell, Mesenchymal Stem Cells, ATMP, Biomaterial, Surgery, [SDV.IB.BIO] Life Sciences [q-bio]/Bioengineering/Biomaterials, Biophysic, Fractures, Ununited, Ceramics and Composites, Feasibility Studies, Bone marrow, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background: ORTHO-1 is a European, multicentric, first in human clinical trial to prove safety and feasibility after surgical implantation of commercially available biphasic calcium phosphate bioceramic granules associated during surgery with autologous mesenchymal stromal cells expanded from bone marrow (BM-hMSC) under good manufacturing practices, in patients with long bone pseudarthrosis. Methods: Twenty-eight patients with femur, tibia or humerus diaphyseal or metaphyso-diaphyseal non-unions were recruited and surgically treated in France, Germany, Italy and Spain with 100 or 200 million BM-hMSC/mL associated with 5–10 cc of bioceramic granules. Patients were followed up during one year. The investigational advanced therapy medicinal product (ATMP) was expanded under the same protocol in all four countries, and approved by each National Competent Authority. Findings: With safety as primary end-point, no severe adverse event was reported as related to the BM-hMSC. With feasibility as secondary end-point, the participating production centres manufactured the BM-hMSC as planned. The ATMP combined to the bioceramic was surgically delivered to the non-unions, and 26/28 treated patients were found radiologically healed at one year (3 out of 4 cortices with bone bridging). Interpretation: Safety and feasibility were clinically proven for surgical implantation of expanded autologous BM-hMSC with bioceramic. Funding: EU-FP7-HEALTH-2009, REBORNE Project (GA: 241876)., The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP7/FP7-HEALTH-2009); REBORNE Project (GA: 241876)

Published
2017

3. Osteoblastic differentiation and potent osteogenicity of three-dimensional hBMSC-BCP particle constructs

Author

Cordonnier, Thomas, Langonné, Alain, Corre, Pierre, Renaud, Audrey, Sensebé, Luc, Rosset, Philippe, Layrolle, Pierre, Sohier, Jérôme, Jehan, Frederic, Regenerating Bone defects using New biomedical Engineering approaches - REBORNE - - EC:FP7:HEALTH2010-01-01 - 2015-06-30 - 241879 - VALID, Physiopathologie des Adaptations Nutritionnelles (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Laboratoire d'hématopoïèse [Tours], Université Francois Rabelais [Tours], Etablissement Français du Sang Centre-Atlantique (EA3855), EFS, Regenerative Medicine and Skeleton (RMeS), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Département de Stomatologie et chirurgie maxillo-faciale [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Etablissement français du sang [Pyrénées-Méditerranée] (EFS Pyrénées-Méditerranée), Départements de chirurgie orthopédique [CHRU Tours], This work was supported by the French National Research Agency (ATOS project) and partially funded by the Directorate-General for Research of the European Commission (Grant No. 241879) through the REBORNE project., European Project: 241879,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,REBORNE(2010), Micro et Nanomédecines Biomimétiques, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL), Theraptosis Research Laboratory, Theraptosis S.A., Regenerative Medicine and Skeleton research lab (RMeS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), STROMALab, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Sarcomes osseux et remodelage des tissus calcifiés - Phy-Os [Nantes] (INSERM U1238), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bretagne Loire (UBL)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Equipe de recherche clinique en Odontologie (ERT1051), Université de Nantes (UN), Micro et Nanomédecines Biomimétiques (MINT), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Université Francois Rabelais [Tours], and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université Francois Rabelais [Tours]

Subjects
Male, three dimensional constructs, biphasic calcium phosphate, Mice, Nude, Real-Time Polymerase Chain Reaction, Mice, Implants, Experimental, Osteogenesis, Animals, Humans, RNA, Messenger, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, bone tissue engineering, ComputingMilieux_MISCELLANEOUS, Aged, Cell Proliferation, Aged, 80 and over, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Osteoblasts, Tissue Scaffolds, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, glass beads, Cell Differentiation, Mesenchymal Stem Cells, Middle Aged, Microspheres, osteogenicity in nude mice, human bone marrow stromal cells, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Female, Hydroxyapatites, osteoblastic differentiation
Abstract

International audience; Bone tissue engineering usually consists of associating osteoprogenitor cells and macroporous scaffolds. This study investigated the in vitro osteoblastic differentiation and resulting in vivo bone formation induced by a different approach that uses particles as substrate for human bone marrow stromal cells (hBMSCs), in order to provide cells with a higher degree of freedom and allow them to synthesize a three-dimensional (3D) environment. Biphasic calcium phosphate (BCP) particles (35 mg, ~175 µm in diameter) were therefore associated with 4 X 10[5] hBMSCs. To discriminate the roles of BCP properties and cell-synthesized 3D environments, inert glass beads (GBs) of similar size were used under the same conditions. In both cases, high cell proliferation and extensive extracellular matrix (ECM) production resulted in the rapid formation of thick cell-synthesized 3D constructs. In vitro, spontaneous osteoblastic differentiation was observed in the 3D constructs at the mRNA and protein levels by monitoring the expression of Runx2, BMP2, ColI, BSP and OCN. The hBMSC–BCP particle constructs implanted in the subcutis of nude mice induced abundant ectopic bone formation after 8 weeks (~35%, n = 5/5). In comparison, only fibrous tissue without bone was observed in the implanted hBMSC–GB constructs (n = 0/5). Furthermore, little bone formation (~3%, n = 5/5) was found in hBMSC–macroporous BCP discs (diameter 8 X 3 mm). This study underlines the lack of correspondence between bone formation and in vitro differentiation assays. Furthermore, these results highlight the importance of using BCP as well as a 3D environment for achieving high bone yield of interest for bone engineering.

Published
2014
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4. Efficacy of acetylleucine in vertigo and dizziness: a systematic review of randomised controlled trials

Author

Florian Naudet, Rémy Boussageon, Helene Vaillant Roussel, Nematollah Jaafari, Clara Blanchard, Denis Pouchain, Paul Vanderkam, Marie Christine Perault-Pochat, Département de Médecine Générale, Université de Poitiers (DMG), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers-Université de Poitiers, Unité de Recherche Clinique [CH Henri Laborit, Poitiers], Centre Hospitalier Henri Laborit (CHL), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Médecine Générale [CHRU Tours], Université Francois Rabelais [Tours]-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), AutomédiCation aCcompagnement Pluriprofessionnel PatienT (ACCePPT), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Departement Médecine Générale [Clermont-Ferrand] (UFR Médecine), Université d'Auvergne - Clermont-Ferrand I (UdA), Service de pharmacologie clinique et de sensibilisation [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupement de recherche en Psychiatrie (GDR Psychiatrie (3557)), Centre National de la Recherche Scientifique (CNRS), 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), VIGNAL, Alexine, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université Francois Rabelais [Tours]

Subjects
medicine.medical_specialty, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Treatment outcome, Pharmacology toxicology, MEDLINE, Placebo, 030226 pharmacology & pharmacy, Dizziness, MESH: Dizziness, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, law, Leucine, Vertigo, otorhinolaryngologic diseases, MESH: vertigo, Medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Medical prescription, Randomized Controlled Trials as Topic, Pharmacology, Randomised controlled trial, Acetylleucine, biology, business.industry, General Medicine, biology.organism_classification, 3. Good health, Physical therapy, MESH: Treatment outcome, MESH: Randomised controlled trial, business, MESH: Acetylleucine, medicine.drug
Abstract

International audience; PURPOSE:To assess the efficacy of acetylleucine to improve or stop an attack of vertigo and dizziness (vertigo/dizziness).METHODS:Systematic review by 2 independent reviewers. Consultation of the Medline, Cochrane and ClinicalTrials.gov databases until September 2018. Keywords used: Acetylleucine, Tanganil®, Acetyl-DL-leucine, Acetyl-leucine. Trial selection: randomised controlled trials (RCTs) comparing acetylleucine against placebo.RESULTS:Up until 2018, no RCTs have been published on the efficacy of acetylleucine in vertigo/dizziness.CONCLUSION:There is no solid evidence of the efficacy of acetylleucine in vertigo/dizziness. Given its frequent prescription and the cost generated for the French social security system, high-quality randomised trials should be carried out to assess its efficacy.

Published
2019

5. Cross-sectional multicentre study on the cohort of all the French junior lecturers in general practice

Author

Catherine Laporte, Marie Barais, Paul Frappé, Tiphanie Bouchez, Clarisse Dibao-Dina, Matthieu Schuers, Julien Gelly, Olivier Saint-Lary, David Darmon, Departement Médecine Générale [Brest] (Faculté de Médecine), Université de Brest (UBO), Soins Primaires, Santé Publique, Registre des cancers de Bretagne Occidentale (EA7479 SPURBO), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Departement Médecine Générale [Clermont-Ferrand] (UFR Médecine), Université d'Auvergne - Clermont-Ferrand I (UdA), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), 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), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Département de Médecine Générale [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Département de Médecine Générale [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université Francois Rabelais [Tours], Département d'Enseignement et de Recherche en Médecine Générale (DERGM), Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Médecine Générale, Université Paris Diderot - Paris 7 (UPD7), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Département de Médecine Générale [Rouen] (DMG), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Team 1: 'Health Services Research' (Inserm U1018 - CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Département de médecine générale, Université Jean Monnet [Saint-Étienne] (UJM), Université Francois Rabelais [Tours]-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Soins Primaires, Santé Publique, Registre des cancers de Bretagne Occidentale (SPURBO), Département de Médecine Générale [Saint-Etienne], Université Jean Monnet - Saint-Étienne (UJM), Dupuis, Christine, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), 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)-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), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)

Subjects
Adult, Male, Faculty, Medical, [SDV]Life Sciences [q-bio], Workload, Primary care, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, 0302 clinical medicine, Qualitative analysis, Surveys and Questionnaires, Health care, Humans, Medicine, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Medical education, lcsh:R5-920, research, business.industry, 4. Education, teaching, Cross-Sectional Studies, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, General practice, Cohort, Mandate, delivery of healthcare, Female, Original Article, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Family Practice, business, lcsh:Medicine (General), Discipline
Abstract

BACKGROUND: General practice became an academic discipline quite recently in many western countries. In France, junior lecturer work is specified in a three-part mandate: medical work in general practice, teaching in the university, and research. Since 2007, 130 junior lecturers have been appointed in general practice. The aim of the creation of junior lecturer status was to align general practice with other specialties and to develop research and education in primary care. OBJECTIVES: To describe the healthcare, teaching and research undertaken by junior lecturers in general practice, practising in October 2014. METHODS: A cross-sectional multicentre study using an online self-administered questionnaire on the cohort composed of all the junior lecturers in general practice with open questions and the qualitative analysis of written verbatim accounts. RESULTS: Of the 95 junior lecturers practising at the date of the study, 75 (79%) responded; average age 32 years; gender ratio (F/M) 2.4:1. They spent five, two and three half-days per week respectively in healthcare, teaching and research. The healthcare activity was predominantly carried out in the community (73%). Thirty-nine per cent worked as part of a multi-professional team taking on 50 consultations per week. Most of the educational work involved lecturing and mentoring students specializing in general practice (median 86 hours per year). Research output increased during the fellowship. Research topics were varied and relevant to the disciplinary field. CONCLUSION: During the fellowship, the balancing, and even the reinforcement, of healthcare and research contributions were accompanied by a significant investment in educational provision.

Published
2018

6. ESCAPE Ancillary Blood Pressure Measurement Study 2: Changes in End-Digit Preference after 2 Years of a Cluster Randomized Trial

Author

Dibao-Dina, Clarisse, Lebeau, Jean-Pierre, Huas, Dominique, Boutitie, Florent, Pouchain, Denis, General Practice, French National College, Département de Médecine Générale [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université Francois Rabelais [Tours], MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Departement Médecine Générale [Tours] (Faculté de Médecine), Université de Tours (UT), Collège National des Généralistes Enseignants (CNGE), 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 Francois Rabelais [Tours]-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, and Université de Tours

Subjects
Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Primary health care, Blood Pressure, Primary care, Intervention group, Assessment and Diagnosis, Disease cluster, Models, Internal medicine, Internal Medicine, Medicine, Cluster Analysis, Humans, Statistical analysis, Cluster randomised controlled trial, Advanced and Specialized Nursing, Models, Statistical, Primary Health Care, business.industry, Blood Pressure Determination, General Medicine, Statistical, Numerical digit, 3. Good health, Surgery, Blood pressure, Hypertension, Female, Cardiology and Cardiovascular Medicine, business
Abstract

International audience; OBJECTIVE: The aim of the ESCAPE AMPA 2 trial was to describe the evolution of end-digit preference (EDP) practices in primary care after 2 years of trial. METHODS: A descriptive analysis of the EDP in the intervention group (IG) and in the electronic control group (ECG) of the ESCAPE trial and a comparative analysis of EDP changes in blood pressure (BP) measures of both groups were carried out between baseline and 2 years. In the ESCAPE trial, physicians in the IG were new users of electronic devices provided in the trial to measure their patients' BP and physicians in the ECG were former users of electronic devices. Hierarchical mixed-effects models were used for statistical analysis in a pragmatic cluster randomized-controlled trial. RESULTS: After 2 years, the proportion of BP measures ending with a 0 or a 5 was significantly higher in the ECG than in the IG (50.4 vs. 33.4%, P

Published
2015

7. Unbalanced Rather than Balanced Randomized Controlled Trials Are More Often Positive in Favor of the New Treatment: An Exposed and Nonexposed Study

Author

A. Caille, B. Giraudeau, C. Dibao, Département de Médecine Générale [CHRU Tours], Université Francois Rabelais [Tours]-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Francois Rabelais [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université Francois Rabelais [Tours], Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Randomization Ratio, medicine.medical_specialty, Randomization, Data Interpretation, Epidemiology, Investigational, [SDV]Life Sciences [q-bio], Population, Meta-study, MEDLINE, 030204 cardiovascular system & hematology, Clinical equipoise, law.invention, 03 medical and health sciences, 0302 clinical medicine, Primary outcome, Randomized controlled trial, law, health services administration, Statistics, medicine, Humans, 030212 general & internal medicine, education, Randomized Controlled Trials as Topic, Ethics, education.field_of_study, business.industry, Therapies, Investigational, Odds ratio, Statistical, Confidence interval, 3. Good health, Unbalanced randomization, ArtThese, P-value, Research Design, Data Interpretation, Statistical, Therapies, Therapeutic Equipoise, Physical therapy, Randomized controlled trials, Observational study, Cardiology and Cardiovascular Medicine, business, 030217 neurology & neurosurgery
Abstract

Introduction Clinical equipoise (i.e., uncertainty within the expert clinical community) is considered as a prerequisite for a randomized controlled trial (RCT). Indeed, a RCT must start with an “honest null hypothesis”, which indicates controversy in the clinical expert community about the superiority of one of the 2 compared interventions. At the planning stage, randomization may reflect the clinical uncertainty, namely, by the randomization ratio. A 1:1 ratio appears to best fit this state of uncertainty. Objective We aimed to assess whether the clinical equipoise principle is satisfied in unbalanced RCTs (i.e., with an unequal probability of subjects being allocated to one group than another). Method Observational and comparative study between unbalanced and balanced RCTs. We searched the “core clinical journals” of MEDLINE to identify reports of two-parallel–group superiority unbalanced RCTs published between January 2009 and December 2010. For each unbalanced RCT, we identified a maximum of 4 reports (to maximize power) of matched balanced RCTs dealing with the same population. Our primary outcome was the proportion of positive RCTs (i.e., with statistically significant results for the primary outcome [P Results We selected 46 reports of unbalanced RCTs and 164 of balanced RCTs; 65.2% unbalanced RCTs and 43.9% of balanced RCTs were positive [odds ratio 2.38; 95% confidence interval: 1.23, 4.63]. As compared with balanced RCTs, unbalanced RCTs were more often industry-funded and their control treatments were more often inactive. Adjusting for these latter variables did not modify the results. Conclusion This result questions the respect of clinical equipoise in unbalanced RCTs.

Published
2015

8. Somatostatin Receptors 2A and 5 Are Expressed in Merkel Cell Carcinoma with No Association with Disease Severity

Author

Ewa Wierzbicka, Agnès Caille, Eric Estève, Serge Guyétant, Gérard Lorette, François Aubin, Antoine Touzé, Martine Avenel-Audran, Pierre Coursaget, Nathalie Beneton, Rémy Kerdraon, C. Gardair, Anne Croué, Mahtab Samimi, Département de Pathologie, Université Francois Rabelais [Tours]-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), UR Infectiologie animale et Santé publique (UR IASP), Institut National de la Recherche Agronomique (INRA), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), CIC 1415, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Francois Rabelais [Tours], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Département de Dermatologie, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Centre Hospitalier Régional d'Orléans (CHR), Centre Hospitalier du Mans, Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Francois Rabelais [Tours]-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Régional d'Orléans (CHRO), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Université Francois Rabelais [Tours], Institut National de la Recherche Agronomique (INRA)-Université de Tours, and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Pathology, medicine.medical_specialty, Skin Neoplasms, Endocrinology, Diabetes and Metabolism, Severity of Illness Index, Disease-Free Survival, Somatostatin receptor, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Endocrinology, Merkel cell carcinoma, Disease severity, Internal medicine, medicine, Carcinoma, Humans, Receptors, Somatostatin, Receptor, Aged, 030304 developmental biology, Outcome, Aged, 80 and over, 0303 health sciences, integumentary system, Endocrine and Autonomic Systems, business.industry, Ki67 proliferative index, food and beverages, medicine.disease, Immunohistochemistry, Neuroendocrine tumour, Carcinoma, Merkel Cell, Somatostatin, 030220 oncology & carcinogenesis, Female, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background/Aims: Merkel cell carcinoma (MCC) is a rare high-grade neuroendocrine tumour of the skin. It has been speculated that MCCs express somatostatin receptors (SSTRs), but this has never been assessed in a large series of MCCs. The main aim of this study was to assess the expression of SSTR2A and SSTR5 in MCC tumours. The secondary aims were to assess whether expression of SSTR was associated with the Ki67 proliferative index, Merkel cell polyomavirus (MCPyV) status, clinical characteristics and outcome. Methods: Clinical data and tumours were collected from an ongoing cohort of French patients with MCC. Immunohistochemistry was performed with anti-SSTR2A and anti-SSTR5 monoclonal antibodies, and tumours were classified into 3 groups: ‘no expression', ‘low expression' and ‘moderate expression' using an SSTR staining score. Results: SSTR expression was assessed for 105 MCC tissue samples from 98 patients, and clinical characteristics were available for 87 of them. SSTR expression was consistent between the primary skin tumour and the corresponding metastases for SSTR2A and SSTR5 in 3/7 and 6/7 cases, respectively. SSTR2A and SSTR5 were expressed in 58 cases (59.2%) and in 44 cases (44.9%), respectively. Overall, at least one SSTR was expressed in 75 tumours (76.5%). SSTR expression was not associated with clinical characteristics, Ki67 proliferative index, recurrence-free survival or MCC-specific survival. Expression of SSTR2A was associated with MCPyV status in MCC tumours but not SSTR5. Conclusion: SSTRs were expressed in a high proportion of MCCs, although expression was heterogeneous between tumours and was not associated with disease severity.

Published
2015

9. Devenir des grossesses uniques après transfert au stade blastocyste : comparaison avec les transferts précoces

Author

Fabrice Guerif, Cynthia Frapsauce, Dominique Royere, L. Martin, Ecole Régionale de sages Femmes de Tours, Université Francois Rabelais [Tours]-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine et Biologie de la Reproduction, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Francois Rabelais [Tours]-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]-Institut National de la Recherche Agronomique (INRA), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Université Francois Rabelais [Tours]

Subjects
Gynecology, 0303 health sciences, medicine.medical_specialty, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], 030219 obstetrics & reproductive medicine, business.industry, blastocyst, congenital malformation, Obstetrics and Gynecology, birth weight, Congenital malformations, General Medicine, sex ratio, 03 medical and health sciences, 0302 clinical medicine, Reproductive Medicine, Cleavage stage, Medicine, early cleavage stage, pregnancy, delivery, business, 030304 developmental biology
Abstract

Resume Objectifs Le transfert frais de blastocystes a montre son interet dans la prise en charge des couples en FIV. Or peu de donnees ont ete publiees sur le deroulement de la grossesse et l’etat des enfants nes. Ce travail compare le deroulement de la grossesse, l’accouchement et l’etat des enfants a la naissance apres transfert au stade blastocyste avec le transfert embryonnaire precoce (a j2). Patientes et methodes Il s’agit d’une etude retrospective menee au sein du service d’AMP du CHRU de Tours de janvier 2002 a juin 2009. Il a ete compare le devenir de 1547 grossesses uniques chez des femmes primipares et de meme âge issues d’un transfert au stade blastocyste ( n = 588) ou au stade precoce a j2 ( n = 959). Les donnees proviennent de l’analyse des fiches grossesses FIVNAT retournees volontairement par les couples. Resultats Avec un retour de fiches grossesses FIVNAT de 97,6 %, nous avons observe que le deroulement de la grossesse, le sex-ratio, le poids de naissance et l’etat de l’enfant a la naissance n’etaient pas affectes par le stade embryonnaire transfere dans le cadre de grossesses uniques. Discussion et conclusion En ce qui concerne le deroulement de la grossesse, l’accouchement et l’etat des enfants nes apres transfert au stade blastocyste, les donnees de la litterature sont peu abondantes, souvent controversees et associant grossesses uniques et multiples. Les resultats de cette etude sont certes rassurants, mais doivent etre confirmees par d’autres series.

Published
2012

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