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301. Recommendations of the French society of rheumatology for the pharmacological management of knee osteoarthritis

Author: Alice Courties, F. Eymard, H.K. Ea, Xavier Chevalier, Jérémy Maillet, Paul Ornetti, E. Senbel, Francis Berenbaum, B. Bannwarth, L. Baumann, H. Lellouche, Romain Forestier, François Rannou, Augustin Latourte, C. Roux, A.-C. Rat, Jérémie Sellam, Didier Mainard, Laurent Grange, M.-C. Fabre, S. Ferrero, Pascal Richette, Serge Perrot, Sorbonne Université - Faculté de Médecine - École de sages-femmes Saint-Antoine (SU ESF), Sorbonne Université (SU), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Archet 2 [Nice] (CHU), Hôpital Lariboisière, Service de Rhumatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU de Bordeaux Pellegrin [Bordeaux], Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Association Française de Lutte Anti-Rhumatismale (AFLAR), Aubert & Duval, Centre de recherche rhumatologiques et thermales, Aix-les-Bains, Service de Rhumatologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Hôpital de Brabois, CHU de Nancy, Vandoeuvre-lès-Nancy, Centre d'Evaluation et de traitement de la douleur, AP-HP, Hôpital Cochin, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], CHU Cochin [AP-HP], Cabinet Médical de Rhumatologie, Marseille, Osteoarthritis Res Soc Int, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Hôpital Cochin [AP-HP]
Subjects: 0303 health sciences, medicine.medical_specialty, business.industry, Pharmacological management, education, Biomedical Engineering, Osteoarthritis, medicine.disease, Rheumatology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, 030220 oncology & carcinogenesis, Expert opinion, Internal medicine, medicine, Physical therapy, Orthopedics and Sports Medicine, business, health care economics and organizations, 030304 developmental biology
Abstract: International audience; Purpose: To establish on behalf of the French Society of Rheumatology (SFR) recommendationson pharmacological treatments (drugs and medical devices) for knee osteoarthritis(KOA) by an evidence-based medicine and expert opinion approach.
Published: 2019

302. Evaluation of the Needle Positioning Accuracy of a Light Puncture Robot Under MRI Guidance: Results of a Clinical Trial on Healthy Volunteers

Author: Ivan Bricault, Maud Medici, Emilie Chipon, Alexandre Moreau-Gaudry, Céline Fouard, Nikolai Hungr, Baptiste Veron, Philippe Cinquin, Julien Ghelfi, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire [Grenoble] (CHU), Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre d'Investigation Clinique [Grenoble] (CIC Grenoble ), CHU Grenoble-Hôpital Michallon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre d'Investigation Clinique - Innovation Technologique - INSERM - CHU de Grenoble (CIC-IT Grenoble (CIT803)), CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), and Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi)
Subjects: Adult, Male, medicine.medical_specialty, Percutaneous, Robot, [SDV]Life Sciences [q-bio], 0206 medical engineering, Pilot Projects, 02 engineering and technology, Punctures, Radiology, Interventional, Placebos, 03 medical and health sciences, User-Computer Interface, MRI guidance, 0302 clinical medicine, Physical medicine and rehabilitation, Robotic Surgical Procedures, Healthy volunteers, Abdomen, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Procedure time, business.industry, Ultrasound, Equipment Design, 020601 biomedical engineering, Healthy Volunteers, 3. Good health, Clinical trial, Needles, Percutaneous interventions, 030220 oncology & carcinogenesis, Female, Cardiology and Cardiovascular Medicine, business
Abstract: International audience; PURPOSE:To assess the accuracy of Light Puncture Robot (LPR) as a patient-mounted robot, in positioning a sham needle under MRI guidance for abdominal percutaneous interventions.MATERIALS AND METHODS:This monocentric, prospective and non-controlled study was approved by the ethics review board. The study evaluated the accuracy of LPR V3 to achieve a virtual puncture in 20 healthy volunteers. Three trajectories were tried on each volunteer, under 3-T MRI guidance.RESULTS:Accuracy under 5 mm in attaining a 10 cm-deep target was reached in 72% of attempts after 2 robot motions with a median error of 4.1 mm [2.1; 5.1]. Median procedure time for one trajectory was 12.9 min [10.2; 18.0] and median installation time was 9.0 min [6.0; 13.0].CONCLUSION:LPR accuracy in the deployment of a sham needle inside the MRI tunnel and its setup time are promising. Further studies need to be conducted to confirm these results before clinical trials.
Published: 2017

303. Exploring venlafaxine pharmacokinetic variability with a phenotyping approach, a multicentric french-swiss study (MARVEL study)

Author: Philippe Le Corvoisier, Jules Alexandre Desmeules, Célia Lloret-Linares, Jean-Luc Cracowski, Wissam El-Hage, L. Yon, Kyle Heron, Frank Bellivier, Frédéric Haesebaert, Siamak Davani, Damien Montange, Thomas Desmidt, Olivier Doumy, Antoine Yrondi, Fanny Moliere, Raphaëlle-Marie Richieri, Philippe Vignaud, Sophie Morange, Marie Besson, Sylvie Chevret, Isabelle Nieto, Marion Leboyer, Jérôme Holtzmann, F. Galtier, Fabienne Calvas, Julien Déglon, Pierre-Michel Llorca, Emmanuel Haffen, Philippe Courtet, Youssef Daali, Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Pathologies du système nerveux : recherche épidémiologique et clinique, Université Montpellier 1 ( UM1 ) -IFR76-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de pharmacologie et innovation dans le diabète ( CPID ), Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Centre National de la Recherche Scientifique ( CNRS ), Centre d'Investigation Clinique ( CIC ), Hospices Civils de Lyon ( HCL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU de Lyon, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne ( NPsy-Sydo ), CHU Clermont-Ferrand-Université Clermont Auvergne ( UCA ), Clinique Psychiatrique Universitaire [Tours], CHRU Tours, Imagerie et cerveau, Université de Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hypoxie : Physiopathologie Respiratoire et Cardiovasculaire ( HP2 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, 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 ), CIC - CHU Henri Mondor, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), UR 1341 Alimentation et adaptations digestives, nerveuses et comportementales, Institut National de la Recherche Agronomique ( INRA ) -Alimentation Humaine ( ALIM.H ) -Alimentation et adaptations digestives, nerveuses et comportementales ( ADNC ), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] ( CAPS ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Geneva University Hospital (HUG), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), 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)-Université de Paris (UP), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Assistance Publique - Hôpitaux de Marseille (APHM), CHU Clermont-Ferrand, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), 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-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Laval [Québec] (ULaval), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre d'Investigation Clinique [Grenoble] (CIC Grenoble ), CHU Grenoble-Hôpital Michallon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Fondation FondaMental [Créteil], CHU Toulouse [Toulouse], Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre d'investigation clinique de Toulouse (CIC 1436), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique Henri Mondor (CIC Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Bordeaux [Bordeaux], University of Bristol [Bristol], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Lausanne University Hospital, Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] (CAPS), Université de Bourgogne (UB)-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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), 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), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Douhairie, Marie-Laurence, 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, Oncology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Venlafaxine, Pharmacology, 030226 pharmacology & pharmacy, ATP-Binding Cassette, Sub-Family B, Member 1/metabolism, Adolescent, Adult, Aged, Aged, 80 and over, Antidepressive Agents, Second-Generation/blood, Antidepressive Agents, Second-Generation/pharmacokinetics, Antidepressive Agents, Second-Generation/therapeutic use, Cytochrome P-450 CYP2C19/metabolism, Cytochrome P-450 CYP2D6/metabolism, Cytochrome P-450 CYP3A/metabolism, Depressive Disorder, Major/drug therapy, Depressive Disorder, Major/metabolism, Female, France, Genotype, Humans, Middle Aged, Phenotype, Switzerland, Treatment Outcome, Venlafaxine Hydrochloride/blood, Venlafaxine Hydrochloride/pharmacokinetics, Venlafaxine Hydrochloride/therapeutic use, Young Adult, Study Protocol, [ SDV.NEU.SC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 0302 clinical medicine, 80 and over, Cytochrome P-450 CYP3A, Medicine, Pharmacology (medical), Major depressive episode, ComputingMilieux_MISCELLANEOUS, ddc:615, ddc:617, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Venlafaxine Hydrochloride, Area under the curve, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Antidepressive Agents, 3. Good health, Cytochrome P-450 CYP2D6, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [ SCCO.NEUR ] Cognitive science/Neuroscience, Antidepressive Agents, Second-Generation, medicine.symptom, medicine.drug, CYP2D6, medicine.medical_specialty, Major/drug therapy/metabolism, CYP2C19, [ SDV.NEU.PC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, 03 medical and health sciences, Pharmacokinetics, lcsh:RA1190-1270, Internal medicine, Member 1/metabolism, ATP Binding Cassette Transporter, Subfamily B, Member 1, Dosing, lcsh:Toxicology. Poisons, Second-Generation/blood/pharmacokinetics/therapeutic use, Depressive Disorder, Depressive Disorder, Major, Sub-Family B, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, lcsh:RM1-950, [SCCO.NEUR] Cognitive science/Neuroscience, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Cytochrome P-450 CYP2C19, lcsh:Therapeutics. Pharmacology, Venlafaxine Hydrochloride/blood/pharmacokinetics/therapeutic use, ATP-Binding Cassette, Personalized medicine, business, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 030217 neurology & neurosurgery
Abstract: It is well known that the standard doses of a given drug may not have equivalent effects in all patients. To date, the management of depression remains mainly empirical and often poorly evaluated. The development of a personalized medicine in psychiatry may reduce treatment failure, intolerance or resistance, and hence the burden and costs of mood depressive disorders. The Geneva Cocktail Phenotypic approach presents several advantages including the “in vivo” measure of different cytochromes and transporter P-gp activities, their simultaneous determination in a single test, avoiding the influence of variability over time on phenotyping results, the administration of low dose substrates, a limited sampling strategy with an analytical method developed on DBS analysis. The goal of this project is to explore the relationship between the activity of drug-metabolizing enzymes (DME), assessed by a phenotypic approach, and the concentrations of Venlafaxine (VLX) + O-demethyl-venlafaxine (ODV), the efficacy and tolerance of VLX. This study is a multicentre prospective non-randomized open trial. Eligible patients present a major depressive episode, MADRS over or equal to 20, treatment with VLX regardless of the dose during at least 4 weeks. The Phenotype Visit includes VLX and ODV concentration measurement. Following the oral absorption of low doses of omeprazole, midazolam, dextromethorphan, and fexofenadine, drug metabolizing enzymes activity is assessed by specific metabolite/probe concentration ratios from a sample taken 2 h after cocktail administration for CYP2C19, CYP3A4, CYP2D6; and by the determination of the limited area under the curve from the capillary blood samples taken 2–3 and 6 h after cocktail administration for CYP2C19 and P-gp. Two follow-up visits will take place between 25 and 40 days and 50–70 days after inclusion. They include assessment of efficacy, tolerance and observance. Eleven french centres are involved in recruitment, expected to be completed within approximately 2 years with 205 patients. Metabolic ratios are determined in Geneva, Switzerland. By showing an association between drug metabolism and VLX concentrations, efficacy and tolerance, there is a hope that testing drug metabolism pathways with a phenotypical approach would help physicians in selecting and dosing antidepressants. The MARVEL study will provide an important contribution to increasing the knowledge of VLX variability and in optimizing the use of methods of personalized therapy in psychiatric settings. ClinicalTrials.gov NCT02590185 (10/27/2015). This study is currently recruiting participants.
Published: 2017

304. Anticancer properties of sodium selenite in human glioblastoma cell cluster spheroids

Author: François Laporte, Pierre Champelovier, Jean Boutonnat, Catherine Garrel, Edwige Col, Josiane Arnaud, Cécile Cottet, Patrice Faure, Florence Hazane-Puch, Sylvie Berthier, Département de biologie intégrée, CHU Grenoble-Hôpital Michallon, Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: 0301 basic medicine, Programmed cell death, Cell cycle checkpoint, [SDV]Life Sciences [q-bio], Apoptosis, DNA Fragmentation, Biochemistry, Epigenesis, Genetic, Inorganic Chemistry, 03 medical and health sciences, Necrosis, 0302 clinical medicine, Sodium Selenite, In vivo, Antigens, Neoplasm, Cell Line, Tumor, Spheroids, Cellular, medicine, Humans, Neoplasm Invasiveness, RNA, Messenger, Carbonic Anhydrase IX, Cell Aggregation, Cell Proliferation, Matrigel, Temozolomide, Chemistry, Caspase 3, Cell Cycle, Cadherins, 3. Good health, Enzyme Activation, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Cell culture, 030220 oncology & carcinogenesis, Cancer cell, Cancer research, Molecular Medicine, Glioblastoma, medicine.drug
Abstract: International audience; Glioblastoma (GBM) is the most common type of primary tumor of the central nervous system with a poor prognosis, needing the development of new therapeutic drugs. Few studies focused on sodium selenite (SS) effects in cancer cells cultured as multicellular tumor spheroids (MCTS or 3D) closer to in vivo tumor. We investigated SS anticancer effects in three human GBM cell lines cultured in 3D: LN229, U87 (O(6)-methyguanine-DNA-methyltransferase (MGMT) negative) and T98G (MGMT positive). SS absorption was evaluated and the cytotoxicity of SS and temozolomide (TMZ), the standard drug used against GBM, were compared. SS impacts on proliferation, cell death, and invasiveness were evaluated as well as epigenetic modifications by focusing on histone deacetylase (HDAC) activity and dimethyl-histone-3-lysine-9 methylation (H3K9m2), after 24h to 72h SS exposition. SS was absorbed by spheroids and was more cytotoxic than TMZ (i.e., for LN229, the IC50 was 38 fold-more elevated for TMZ than SS, at 72h). SS induced a cell cycle arrest in the S phase and apoptosis via caspase-3. SS decreased carbonic anhydrase-9 (CA9) expression, invasion on a Matrigel matrix and modulated E- and N-Cadherin transcript expressions. SS decreased HDAC activity and modulated H3K9m2 levels. 3D model provides a relevant strategy to screen new drugs and SS is a promising drug against GBM that should now be tested in GBM animal models.
Published: 2017

305. Reactive oxygen species levels control NF-κB activation by low dose deferasirox in erythroid progenitors of low risk myelodysplastic syndromes

Author: Meunier, Mathieu, Ancelet, Sarah, Lefebvre, Christine, Arnaud, Josyane, Garrel, Catherine, Pezet, Mylène, Wang, Yan, Faure, Patrice, Szymanski, Gautier, Duployez, Nicolas, Preudhomme, Claude, Biard, Denis, Polack, Benoît, Cahn, Jean-Yves, Moulis, Jean Marc, Park, Sophie, Université du Québec à Montréal = University of Québec in Montréal (UQAM), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire [Grenoble] (CHU), Unité de Biochimie Hormonale et Nutritionnelle, Département de Biologie - Toxicologie - Pharmacologie, Centre d'Explorations Fonctionnelles Intégré (CEFI), Institut National de la Santé et de la Recherche Médicale (INSERM), Leibniz Universität Hannover=Leibniz University Hannover, Institut de Biologie et de Pathologie (DBTP), CHU Grenoble, Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de Radiobiologie Cellulaire et Moléculaire (IRCM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), Département de cancérologie et d'hématologie, CHU Grenoble-Hôpital Michallon, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Grenoble, Leibniz Universität Hannover [Hannover] (LUH), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

306. Sound levels in a neonatal intensive care unit significantly exceeded recommendations, especially inside incubators

Author: Descamps, Claire Sophie, Chevallier, Marie, Pin, Isabelle, Epiard, Chloé, Parra, Johanna, de Suremain, Aurelie, Berne Audeoud, Frederique, Ego, Anne, Debillon, Thierry, Science et Technologie du Lait et de l'Oeuf (STLO), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Techniques pour l'Evaluation et la Modélisation des Actions de la Santé (TIMC-IMAG-ThEMAS), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Département de médecine aiguë spécialisée, CHU Grenoble-Hôpital Michallon, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Registre des Handicaps de l'Enfant et Observatoire Périnatal Isère, RHEOP, Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), CHU Chambéry, Centre Hospitalier Universitaire [Grenoble] (CHU), and Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: Male, Pediatrics, medicine.medical_specialty, Neonatal intensive care unit, Sensory development, health care facilities, manpower, and services, education, Audiology, Medical care, MESH: Noise, Incubators, 03 medical and health sciences, 0302 clinical medicine, Sound levels, Intensive Care Units, Neonatal, 030225 pediatrics, Humans, Medicine, Prospective Studies, Noise level, Sound (geography), Decibel, Incubator noise, geography, Decibels, 030219 obstetrics & reproductive medicine, geography.geographical_feature_category, MESH: Humans, business.industry, MESH: Infant, Newborn, Infant, Newborn, Incubator, General Medicine, Noise metrics, MESH: Incubators, MESH: Male, MESH: Prospective Studies, 3. Good health, Noise, Pediatrics, Perinatology and Child Health, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female, MESH: Intensive Care Units, Neonatal
Abstract: Aim This study measured sound levels in a 2008 built French neonatal intensive care unit (NICU) and compared them to the 2007 American Academy of Pediatrics (AAP) recommendations. The ultimate aim was to identify factors that could influence noise levels. Methods The study measured sound in 17 single or double rooms in the NICU. Two dosimeters were installed in each room, one inside and one outside the incubators, and these conducted measurements over a 24-hour period. The noise metrics measured were the equivalent continuous sound level (Leq), the maximum noise level (Lmax) and the noise level exceeded for 10% of the measurement period (L10). Results The mean Leq, L10 and Lmax were 60.4, 62.1 and 89.1 decibels (dBA), which exceeded the recommended levels of 45, 50 and 65 dBA (p
Published: 2017

307. Evaluation of the clinical benefit of an electromagnetic navigation system for CT-guided interventional radiology procedures in the thoraco-abdominal region compared with conventional CT guidance (CTNAV II): study protocol for a randomised controlled trial

Author: I. Bricault, S. Pottier, S. Aubry, R. C. Rouchy, Mostafa El Hajjam, F. Patat, E. de Kerviler, G. Kervio, M. Durand, X. Orry, R. Logier, A. Cherifi, B. Renard, E. Chipon, A. Moreau-Gaudry, M. Medici, J. Ghelfi, O. Favelle, C. Hughes, Lionel Pazart, B. Lapuyade, E. Quehen, A. Mounier, Centre d'Investigation Clinique - Innovation Technologique - INSERM - CHU de Grenoble (CIC-IT Grenoble (CIT803)), CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Bordeaux [Bordeaux], CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Ambroise Paré [AP-HP], Centre d’Investigation Clinique 1429 [Garches] (CIC 1429), Hôpital Raymond Poincaré [AP-HP]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301 (CIC Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [Tours], 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), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service central de radiologie et d'imagerie médicale, CHU Grenoble-Hôpital Michallon, This trial is funded by the French Ministry of Health as part of the Hospital Clinical Research Program (PHRC-N 2012)., 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), 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: Time Factors, Percutaneous, Active Comparator, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Medicine (miscellaneous), Radiography, Interventional, 030218 nuclear medicine & medical imaging, law.invention, Study Protocol, 0302 clinical medicine, Clinical Protocols, Randomized controlled trial, law, Electromagnetic navigation, Abdomen, Pharmacology (medical), Prospective Studies, Medical device, lcsh:R5-920, medicine.diagnostic_test, Interventional radiology, Equipment Design, Radiation Exposure, Thorax, 3. Good health, Needles, Research Design, 030220 oncology & carcinogenesis, Radiographic Image Interpretation, Computer-Assisted, France, Computer-assisted medical intervention, lcsh:Medicine (General), Electromagnetic Phenomena, medicine.medical_specialty, IMACTIS-CT®, Subgroup analysis, Punctures, Radiation Dosage, Imaging guidance, 03 medical and health sciences, Computed Tomography, Predictive Value of Tests, medicine, Humans, Medical physics, Minimally invasive, Protocol (science), business.industry, Navigation system, Surgery, Clinical trial, Tomography, X-Ray Computed, business, Software
Abstract: Background Interventional radiology includes a range of minimally invasive image-guided diagnostic and therapeutic procedures that have become routine clinical practice. Each procedure involves a percutaneous needle insertion, often guided using computed tomography (CT) because of its availability and usability. However, procedures remain complicated, in particular when an obstacle must be avoided, meaning that an oblique trajectory is required. Navigation systems track the operator’s instruments, meaning the position and progression of the instruments are visualised in real time on the patient’s images. A novel electromagnetic navigation system for CT-guided interventional procedures (IMACTIS-CT®) has been developed, and a previous clinical trial demonstrated improved needle placement accuracy in navigation-assisted procedures. In the present trial, we are evaluating the clinical benefit of the navigation system during the needle insertion step of CT-guided procedures in the thoraco-abdominal region. Methods/design This study is designed as an open, multicentre, prospective, randomised, controlled interventional clinical trial and is structured as a standard two-arm, parallel-design, individually randomised trial. A maximum of 500 patients will be enrolled. In the experimental arm (navigation system), the procedures are carried out using navigation assistance, and in the active comparator arm (CT), the procedures are carried out with conventional CT guidance. The randomisation is stratified by centre and by the expected difficulty of the procedure. The primary outcome of the trial is a combined criterion to assess the safety (number of serious adverse events), efficacy (number of targets reached) and performance (number of control scans acquired) of navigation-assisted, CT-guided procedures as evaluated by a blinded radiologist and confirmed by an expert committee in case of discordance. The secondary outcomes are (1) the duration of the procedure, (2) the satisfaction of the operator and (3) the irradiation dose delivered, with (4) subgroup analysis according to the expected difficulty of the procedure, as well as an evaluation of (5) the usability of the device. Discussion This trial addresses the lack of published high-level evidence studies in which navigation-assisted CT-guided interventional procedures are evaluated. This trial is important because it addresses the problems associated with conventional CT guidance and is particularly relevant because the number of interventional radiology procedures carried out in routine clinical practice is increasing. Trial registration ClinicalTrials.gov identifier: NCT01896219. Registered on 5 July 2013. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2049-6) contains supplementary material, which is available to authorized users.
Published: 2017

308. Interest of intra-operative 3D imaging in spine surgery: a prospective randomized study

Author: E. Chipon, Caroline Dubois, Michel Milaire, G. Kerschbaumer, A. Moreau-Gaudry, P Merloz, Jérôme Tonetti, Sébastien Ruatti, Centre Hospitalier Universitaire [Grenoble] (CHU), Service central de radiologie et d'imagerie médicale, CHU Grenoble-Hôpital Michallon, Centre d'Investigation Clinique - Innovation Technologique - INSERM - CHU de Grenoble (CIC-IT Grenoble (CIT803)), CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), and Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: medicine.medical_specialty, Percutaneous, Intra operative, [SDV]Life Sciences [q-bio], Navigation and spine surgery, 3D fluoroscope, law.invention, 03 medical and health sciences, Spine surgery, 0302 clinical medicine, Randomized controlled trial, 3D imaging, law, Medicine, Orthopedics and Sports Medicine, Prospective randomized study, Computer-aided surgery, Pedicle screw, book, 030222 orthopedics, business.industry, Computer aided surgery, 3. Good health, Surgery, book.journal, Neurosurgery, Radiology, business, 030217 neurology & neurosurgery
Abstract: International audience; We report a single-center, prospective, randomized study for pedicle screw insertion in opened and percutaneous spine surgeries, using a computer-assisted surgery (CAS) technique with three-dimensional (3D) intra-operative images intensifier (without planification on pre-operative CT scan) vs conventional surgical procedure.MATERIAL AND METHOD:We included 143 patients: Group C (conventional, 72 patients) and Group N (3D Fluoronavigation, 71 patients). We measured the pedicle screw running time, and surgeon's radiation exposure. All pedicle runs were assessed according to Heary by two independent radiologists on a post-operative CT scan.RESULTS:3D Fluoronavigation appeared less accurate in percutaneous procedures (24 % of misplaced pedicle screws vs 5 % in Group C) (p = 0.007), but more accurate in opened surgeries (5 % of misplaced pedicle screws vs 17 % in Group C) (p = 0.025). For one vertebra, the average surgical running time reached 8 min in Group C vs 21 min in Group N for percutaneous surgeries (p = 3.42 × 10(-9)), 7.33 min in Group C vs 16.33 min in Group N (p = 2.88 × 10(-7)) for opened surgeries. The 3D navigation device delivered less radiation in percutaneous procedures [0.6 vs 1.62 mSv in Group C (p = 2.45 × 10(-9))]. For opened surgeries, it was twice higher in Group N with 0.21 vs 0.1 mSv in Group C (p = 0.022).CONCLUSION:The rate of misplaced pedicle screws with conventional techniques was nearly the same as most papers and a little bit higher with CAS. Surgical running time and radiation exposure were consistent with many studies. Our work hypothesis is partially confirmed, depending on the type of surgery (opened or closed procedure).
Published: 2015

309. Iron for proliferation of cell lines and hematopoietic progenitors: Nailing down the intracellular functional iron concentration

Author: Nicolas Mobilia, Josiane Arnaud, Eric Fanchon, Marine Lénon, Jean-Yves Cahn, Pascal Mossuz, Jean-Marc Moulis, Emmanuel Pourcelot, Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie Computationnelle et Mathématique (TIMC-IMAG-BCM), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Département de cancérologie et d'hématologie, CHU Grenoble-Hôpital Michallon, Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Centre Hospitalier Universitaire [Grenoble] (CHU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Région Rhône Alpes (Programme Cible 2010), Institut Rhône-Alpin des systèmes complexes (IXXI), UJF Grenoble (Programme Agir 2013), Recherche Clinique CHU Grenoble (DRC), Novartis, and Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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)
Subjects: Cell division, [SDV]Life Sciences [q-bio], Iron, Intracellular Space, Transferrin receptor, Antigens, CD34, Cell cycle, Iron Chelating Agents, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Iron homeostasis, Humans, Progenitor cell, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Cell Proliferation, chemistry.chemical_classification, 0303 health sciences, Leukemia, biology, Cell growth, Post-transcriptional regulation, Cellular growth, Modeling, Transferrin, Cell Cycle Checkpoints, Cell Biology, Hematopoietic Stem Cells, Ferritin, Biochemistry, chemistry, 030220 oncology & carcinogenesis, biology.protein, Apoproteins, Intracellular
Abstract: Iron is an essential nutrient which must be provided in sufficient amounts to support growth of eukaryotic cells. All organisms devote specialized pathways to ensure proper delivery. Yet, a quantitative assessment of the intra-cellular iron concentration needed to allow the cell cycle to proceed in mammalian cells is missing. Starting from iron-depleted cell lines or primary hematopoietic progenitors prepared with clinically implemented iron chelators, replenishment via transferrin and other iron sources has been quantitatively monitored through the main endogenous markers of the cellular iron status, namely proteins involved in the uptake (transferrin receptor), the storage (ferritin), and the sensing (Iron Regulatory Proteins) of iron. When correlated with measurements of iron concentrations and indicators of growth, this minimally intrusive approach provided an unprecedented estimate of the intracellular iron concentration acting upon iron-centered regulatory pathways. The data were analyzed with the help of a previously developed theoretical treatment of cellular iron regulation. The minimal cellular iron concentration required for cell division was named functional iron concentration (FIC) to distinguish it from previous estimates of the cellular labile iron. The FIC falls in the low nanomolar range for all studied cells, including hematopoietic progenitors. These data shed new light on basic aspects of cellular iron homeostasis by demonstrating that sensing and regulation of iron occur well below the concentrations requiring storage or becoming noxious in pathological conditions. The quantitative assessment provided here is relevant for monitoring treatments of conditions in which iron provision must be controlled to avoid unwanted cellular proliferation.
Published: 2015
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310. Step-down strategy of spacing TNF-blocker injections for established rheumatoid arthritis in remission: results of the multicentre non-inferiority randomised open-label controlled trial(STRASS: Spacing of TNF-blocker injections in Rheumatoid ArthritiS Study)

Author: Violaine Foltz, Jacques Morel, Jean-Marie Berthelot, Toni Alfaiate, Frédérique Gandjbakhch, Xavier Mariette, Emmanuelle Dernis, Jean-Charles Balblanc, Olivier Brocq, Thao Pham, Elisabeth Solau-Gervais, Philippe Gaudin, Bruno Fautrel, Florence Tubach, Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Rhumatologie [Sainte- Marguerite - APHM] ( Hôpitaux Sud), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Département d’Epidémiologie et Recherche Clinique [AP-HP Hôpital Bichat - Claude Bernard] (CIC‑EC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Service de Rhumatologie [CH Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Service de Rhumatologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Hôpital Princesse Grace [Monaco], Service de rhumatologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Poitiers, Service de rhumatologie [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), CH Belfort-Montbéliard, Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Service de Rhumatologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Service de Rhumatologie - CH Le Mans, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris]-Université Paris Diderot - Paris 7 (UPD7), and AP-HP Hôpital universitaire Robert-Debré [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, medicine.medical_specialty, Immunology, Rheumatoid Arthritis, Severity of Illness Index, Drug Administration Schedule, General Biochemistry, Genetics and Molecular Biology, Etanercept, Maintenance Chemotherapy, law.invention, Arthritis, Rheumatoid, Anti-TNF, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Randomized controlled trial, Recurrence, law, Internal medicine, Epidemiology, medicine, Adalimumab, Humans, Immunology and Allergy, 030212 general & internal medicine, Aged, 030203 arthritis & rheumatology, Tumor Necrosis Factor-alpha, business.industry, Middle Aged, medicine.disease, Connective tissue disease, 3. Good health, Surgery, Radiography, Treatment, Treatment Outcome, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Equivalence Trial, Antirheumatic Agents, Rheumatoid arthritis, Female, Open label, business, medicine.drug
Abstract: Tumour necrosis factor (TNF)-blocker tapering has been proposed for patients with rheumatoid arthritis (RA) in remission. OBJECTIVE: The trial aims to compare the effect of progressive spacing of TNF-blocker injections (S-arm) to their maintenance (M-arm) for established patients with RA in remission. METHODS: The study was an 18-month equivalence trial which included patients receiving etanercept or adalimumab at stable dose for ≥1 year, patients in remission on 28-joint Disease Activity Score (DAS28) for ≥6 months and patients with stable joint damage. Patients were randomised into two arms: maintenance or injections spacing by 50% every 3 months up to complete stop. Spacing was reversed to the previous interval in case of relapse, and eventually reattempted after remission was reachieved. The primary outcome was the standardised difference of DAS28 slopes, based on a linear mixed-effects model (equivalence interval set at ±30%). RESULTS: 64 and 73 patients were included in the S-arm and M-arm, respectively, which was less than planned. In the S-arm, TNF blockers were stopped for 39.1%, only tapered for 35.9% and maintained full dose for 20.3%. The equivalence was not demonstrated with a standardised difference of 19% (95% CI -5% to 46%). Relapse was more common in the S-arm (76.6% vs 46.5%, p=0.0004). However, there was no difference in structural damage progression. CONCLUSIONS: Tapering was not equivalent to maintenance strategy, resulting in more relapses without impacting structural damage progression. Further studies are needed to identify patients who could benefit from such a strategy associated with substantial cost savings. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT00780793; EudraCT identifier: 2007-004483-41.
Published: 2015

311. Alternatives to heparin and protamine anticoagulation for cardiopulmonary bypass in cardiac surgery

Author: Aurore Bouraghda, Pierre Albaladejo, Pierre Gillois, Centre Hospitalier Universitaire [Grenoble] (CHU), Service d'anesthésie-réanimation, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Techniques pour l'Evaluation et la Modélisation des Actions de la Santé (TIMC-IMAG-ThEMAS), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), and VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)
Subjects: Ancrod, [STAT.AP]Statistics [stat]/Applications [stat.AP], Danaparoid Sodium, business.industry, medicine.drug_class, Idraparinux, Anticoagulant, [SCCO.COMP]Cognitive science/Computer science, General Medicine, Lepirudin, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Argatroban, Anesthesiology and Pain Medicine, [STAT.ML]Statistics [stat]/Machine Learning [stat.ML], [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], Anesthesia, medicine, Bivalirudin, business, [STAT.ME]Statistics [stat]/Methodology [stat.ME], ComputingMilieux_MISCELLANEOUS, medicine.drug, Discovery and development of direct thrombin inhibitors
Abstract: Heparin anticoagulation followed by protamine reversal is commonly used in cardiopulmonary bypass (CPB) cardiac procedures, but this strategy has some limitations. The primary objective of this study was to determine the reliable alternatives for anticoagulation during CPB for cardiac surgery. For each drug proposed, the secondary objectives were to outline the main advantages and disadvantages, to propose a therapeutic protocol, and to provide a cost-benefit analysis. A systematic review of the literature was performed between September 2012 and December 2013. It was based on the protocol established by the “Cochrane collaboration Handbook”. Twenty articles were analyzed. The Theriaque database from the University Hospital of Grenoble made the economic analysis possible. Seven alternative anticoagulation strategies were considered: danaparoid sodium, lepirudin, argatroban, bivalirudin, ancrod, idraparinux, and EP217609. Danaparoid sodium has issues with individual variability. Several studies (EVOLUTION-ON, CHOOSE-ON) proposed a reliable therapeutic protocol for bivalirudin. Ancrod resulted in an increase in the transfusion of blood products. Direct thrombin inhibitors offer a promising alternative. EP217609 is a synthetic anticoagulant currently undergoing Phase IIa clinical trials. It is an indirect inhibitor of factor Xa, a direct inhibitor of free and bound thrombin, and can be neutralized by avidin. The ideal anticoagulation strategy for cardiac surgery with CPB does not exist. Heparin and protamine remain the gold standard for anticoagulation therapy. To date, bivalirudin is the most promising molecule despite its high cost and lack of a readily available antagonist.
Published: 2015

312. Ultradeep Pyrosequencing of NS3 To Predict Response to Triple Therapy with Protease Inhibitors in Previously Treated Chronic Hepatitis C Patients

Author: Olivier François, Katia Fusillier, Michael G. B. Blum, Jean-Pierre Zarski, Sylvie Larrat, Pauline Tremeaux, Patrice Morand, Réjane Beugnot, Alice Marlu, Jean-Baptiste Claude, Agnès Plages, Om Kulkarni, Anne Signori-Schmuck, Julien Lupo, Hervé Duborjal, Vincent Leroy, Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Centre National de la Recherche Scientifique (CNRS)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Université Joseph Fourier - Grenoble 1 (UJF), Biologie Computationnelle et Mathématique (TIMC-IMAG-BCM), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Genostar, GENOME Express (GENOME Express), GENOME Express, Earth and Environmental, AMEC, Biochimie et Génétique Moléculaire, CHU Grenoble-Hôpital Michallon, Pôle Digidune, Pôle DigiDune, Unité de Biophysique, CRSSA, Département d'hépato-gastroentérologie, Université Grenoble Alpes (UGA)-CHU Grenoble, Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), CHU Grenoble-Université Grenoble Alpes (UGA), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, and Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Microbiology (medical), NS3, medicine.medical_specialty, Entropy, medicine.medical_treatment, Mutation, Missense, Salvage therapy, Viral quasispecies, Viral Nonstructural Proteins, Biology, Antiviral Agents, Peripheral blood mononuclear cell, Gastroenterology, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Virology, Internal medicine, Drug Resistance, Viral, Genotype, medicine, Humans, Protease Inhibitors, Aged, 030304 developmental biology, Aged, 80 and over, Salvage Therapy, 0303 health sciences, Protease, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Genetic Variation, High-Throughput Nucleotide Sequencing, virus diseases, Odds ratio, Hepatitis C, Chronic, Middle Aged, Prognosis, digestive system diseases, Confidence interval, 3. Good health, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], HCV, Immunology, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology
Abstract: Despite the gain in sustained virological responses (SVR) provided by protease inhibitors (PIs), failures still occur. The aim of this study was to determine if a baseline analysis of the NS3 region using ultradeep pyrosequencing (UDPS) can help to predict an SVR. Serum samples from 40 patients with previously nonresponding genotype 1 chronic hepatitis C who were retreated with triple therapy, including a PI, were analyzed. Baseline UDPS of the NS3 gene was performed on plasma and peripheral blood mononuclear cells (PBMC). Mutations conferring resistance to PIs were sought. The overall diversity of the quasispecies was evaluated by calculating the Shannon entropy (SE). Resistance mutations were found in plasma and PBMC but were not discriminating enough to predict an SVR. NS3 quasispecies heterogeneity was significantly lower at baseline in patients achieving an SVR than in those not achieving an SVR (SE of 26.98 ±16.64 x10^3 versus 44.93 ±19.58 x10^3, P =0.0047). With multivariate analysis, the independent predictors of an SVR were fibrosis of stage F <2 (odds ratio [OR], 13.3; 95% confidence interval [CI], 1.25 to 141.096; P < 0.03) and SE below the median (OR, 5.4; 95% CI, 1.22 to 23.87; P < 0.03). More than the presence of minor mutations at the baseline in plasma or in PBMC, the NS3 viral heterogeneity determined by UDPS is an independent factor for an SVR in previously treated patients receiving triple therapy that includes a PI.&nbsp
Published: 2015

313. Tumour size over 3 cm predicts poor short-term outcomes after major liver resection for hilar cholangiocarcinoma. By the HC-AFC-2009 group

Author: Laurence Chiche, Mustapha Adham, Jeanâ€Robert Delpero, Patrick Pessaux, Emmanuel Boleslawski, Daniel Azoulay, Denis Chatelain, Michel Scotté, Karim Boudjema, Alexis Laurent, Jean-Marc Regimbeau, Philippe Bachellier, Gérard Pascal, Jeanâ€Yves Mabrut, Momar Diouf, Olivier Farges, Gennaro Nuzzo, Christian Letoublon, Georges Mantion, Jeanâ€Francois Gigot, Yvesâ€Patrice Le Treut, Artigas Raventos, Francis Navarro, Michel Rivoire, Ahmet Ayav, David Fuks, CHU Amiens-Picardie, CHU Strasbourg, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Chirurgie Viscérale et Digestive [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Paul Brousse, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, 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), Département de chirurgie digestive et de l'urgence, CHU Grenoble-Hôpital Michallon, Hôpital Claude Huriez [Lille], CHU Lille, Centre Léon Bérard [Lyon], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital Edouard Herriot [CHU - HCL], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Chirurgie Digestive Hépatobiliaire et Endocrine [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pontchaillou [Rennes], Service de chirurgie digestive [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpital Beaujon, 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Herrada, Anthony
Subjects: Male, Curative resection, Time Factors, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, medicine.medical_treatment, Kaplan-Meier Estimate, 030230 surgery, Cholangiocarcinoma, 0302 clinical medicine, Risk Factors, Odds Ratio, Registries, Young adult, Aged, 80 and over, Gastroenterology, Middle Aged, Tumor Burden, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Female, France, Adult, medicine.medical_specialty, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Resection, Young Adult, 03 medical and health sciences, medicine, Hepatectomy, Humans, Aged, Retrospective Studies, Chi-Square Distribution, Hepatology, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Retrospective cohort study, Original Articles, Odds ratio, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Surgery, Bile Ducts, Intrahepatic, Logistic Models, Bile Duct Neoplasms, Tumour size, Multivariate Analysis, Lymph Node Excision, business, Chi-squared distribution
Abstract: International audience; INTRODUCTION:As mortality and morbidity after a curative resection remains high, it is essential to identify pre-operative factors associated with an early death after a major resection.METHODS:Between 1998 and 2008, we selected a population of 331 patients having undergone a major hepatectomy including segment I with a lymphadenectomy and a common bile duct resection for a proven hilar cholangiocarcinoma in 21 tertiary centres. The study's objective was to identify pre-operative predictors of early death (30 mm [odds ratio (OR) 2.471 (95% confidence interval (CI) 1.136-7.339), P = 0.001] and major post-operative complication [OR 3.369 (95% CI 1.038-10.938), P = 0.004] were independently associated with death 30 mm was independently associated with death
Published: 2015

314. Femoral Bifurcation Endarterectomy with Transection-Eversion of the Superficial Femoral Artery: Technique and Results

Author: Sébastien Perou, Amandine Elie, Jessica Morel, Jean-Luc Magne, Rafaelle Spear, Augustin Pirvu, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire [Grenoble] (CHU), Département de chirurgie thoracique, vasculaire et endocrinienne, CHU Grenoble-Hôpital Michallon, Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), and Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Critical Illness, Ischemia, Endarterectomy, 030204 cardiovascular system & hematology, 030230 surgery, Revascularization, 03 medical and health sciences, Peripheral Arterial Disease, 0302 clinical medicine, Postoperative Complications, Risk Factors, medicine, Deep Femoral Artery, Vascular Patency, Humans, Aged, Retrospective Studies, Aged, 80 and over, Superficial femoral artery, business.industry, Endovascular Procedures, Retrospective cohort study, General Medicine, Intermittent Claudication, Middle Aged, medicine.disease, 3. Good health, Surgery, Femoral Artery, Treatment Outcome, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, Claudication, business
Abstract: International audience; BACKGROUND:We evaluated the results of femoral bifurcation endarterectomy using the eversion technique with transection of the superficial femoral artery (femoral bifurcation endarterectomy with eversion [FBEE]).METHODS:We included all patients who underwent a femoral revascularization using the eversion technique, with or without antegrade or retrograde revascularization, from January 2006 to December 2015. Data were retrospectively collected. Primary and primary assisted patency (PAP) of the femoral bifurcation were analyzed. Secondary outcomes were 30-day postoperative complications.RESULTS:A total of 129 patients (143 limbs) underwent consecutive FBEE (86.8% men, with a mean age of 69.7 years). Patients presented with claudication (93, 65%) and critical ischemia (46, 32.2%). Primary patency was 96.3%, 94.6%, and 93% at 1, 2, and 5 years, respectively. PAP was 99% at 3 time points. Reintervention was necessary in 8 patients during follow-up. The 30-day mortality was 0.7% (1 patient), and the access complication rate was 18.8% (n = 27), of which only 2.8% (n = 4) were major complications.CONCLUSIONS:This retrospective study confirmed the efficiency and the reproducibility of this technique for the treatment of femoral bifurcation lesions. This technique allowed treating extensive atherosclerotic lesions of the deep femoral artery and may be associated with antegrade and retrograde revascularizations.
Published: 2017

315. Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban

Author: MARLU, Raphaël, Hodaj, Enkelejda, Paris, Adeline, Albaladejo, Pierre, Crackowski, Jean, Pernod, Gilles, Université Grenoble Alpes (UGA), Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Xénobiotiques, Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service d'anesthésie-réanimation, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), and Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: [SDV]Life Sciences [q-bio], [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2017

316. Transrectal ultrasound-guided prostate biopsies vs. magnetic resonance imaging ultrasound fusion targeted biopsies: Who are the best candidates?

Author: Q. Franquet, Elsa Bey, Gaelle Fiard, Jean-Luc Descotes, Jean-Alexandre Long, Jean-Jacques Rambeaud, Olivier Gaget, Centre Hospitalier Universitaire [Grenoble] (CHU), Service de chirurgie, CHU Grenoble-Hôpital Michallon, Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Grenoble Alpes - UFR Médecine (UGA UFRM), and Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: medicine.medical_specialty, medicine.diagnostic_test, business.industry, Urology, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Cancer, Magnetic resonance imaging, Rectal examination, Odds ratio, medicine.disease, Confidence interval, 3. Good health, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, medicine.anatomical_structure, Oncology, Prostate, 030220 oncology & carcinogenesis, Biopsy, medicine, Radiology, business, Original Research
Abstract: Introduction: The aim of this study was to compare the results of ultrasound-guided prostate biopsies (US-PB) and magnetic resonance imaging-ultrasound fusion biopsies (MRI-PB) in two contemporary cohorts and to describe the parameters orienting the choice of technique.Methods: Two contemporary cohorts of patients undergoing US-PB or MR-PB using the Urostation® (Koelis, Grenoble, France) between November 2010 and July 2015 were analyzed retrospectively. Patients with metastatic cancer or recurrence after treatment, saturation biopsies, and US-PB performed after a negative MRI were excluded. Comparison of populations, biopsy results, and clinical and biological parameters guiding the choice of technique were studied on multivariate analysis (logistic regression) taking into account the following confounding factors: age, prostate-specific antigen (PSA) rate, prostatic volume, number of previous biopsies, and abnormal digital rectal examination.Results: One hundred fourteen patients were included in the US-PB group and 118 in the MR-PB group. Prostate cancer was diagnosed among 65 patients in the US-PB group (detection rate 57.0%) and 70 patients in the MR-PB group (detection rate 59.3%) (odds ratio [OR] 3.00; 95% confidence interval [CI] 1.52–6.17; p=0.002). Among the cancers diagnosed in the MR-PB group, 21 were diagnosed by the two targeted biopsy cores only (15.5%). Patients undergoing MR-PB were significantly younger (p=0.0005), with a higher number of previous biopsy sessions (p
Published: 2017

317. Prise en charge diagnostique des uvéites : recommandations d’un groupe d’experts

Author: Philip Bielefeld, Jérémie Sellam, A. Brézin, D. Monnet, Salim Trad, David Bellocq, Patrice Cacoub, Christophe Chiquet, Gilles Kaplanski, D. Sène, Moritz Weber, Laurent Kodjikian, Bahram Bodaghi, David Saadoun, Pascal Sève, Equipe 14, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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 médecine interne et maladies systémiques (SOC 2) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de médecine interne [CHU Pitié-Salpétrière], 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), Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut für Umweltphysik [Bremen] (IUP), Universität Bremen, Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Ophtalmologie [Grenoble], Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Immunologie - Immunopathologie - Immunothérapie (I3), 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), Hôpital Ambroise Paré [AP-HP], Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département STIC [Brest] (STIC), École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Ophtalmologie (CHU de Dijon), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'Ophtalmologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'ophtalmologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Hôpital Ambroise Paré, Centre de Recherche Saint-Antoine (CR Saint-Antoine), CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Pole STIC, ENSTA Bretagne, and CHU Cochin [AP-HP]
Subjects: 030203 arthritis & rheumatology, Gynecology, medicine.medical_specialty, Etiology, business.industry, Epidemiology, [SDV]Life Sciences [q-bio], Gastroenterology, Standardized strategy, Recommendations, Uveitis, 03 medical and health sciences, 0302 clinical medicine, Diagnosis, 030221 ophthalmology & optometry, Internal Medicine, Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, business
Abstract: Pour citer cet article : Sève P, et al. Prise en charge diagnostique des uvéites : recommandations d'un groupe d'experts. Rev Med Interne (2017), http://dx.; International audience; Introduction. – La démarche diagnostique au cours des uvéites n’est pas standardisée. Elle doit prendre en compte l’épidémiologie des uvéites, cibler les affections les plus sévères et/ou les plus fréquentes, et/ou susceptibles de bénéficier d’un traitement spécifique. Ce travail a été réalisé afin de proposer des recommandations pour le diagnostic des uvéites.Méthodes. – Les recommandations ont été établies par un groupe de 15 experts, internistes, ophtalmo- logistes et rhumatologues, à partir d’une revue de la littérature et de l’étude ULISSE qui est la première étude prospective à avoir évalué une stratégie diagnostique pour les uvéites. Sont exclues de ces recom- mandations les uvéites de l’enfant, de l’immunodéprimé, les vascularites rétiniennes sévères et les entités purement ophtalmologiques.Résultats. – Le bilan paraclinique doit en premier lieu être orienté par les éléments de l’interrogatoire et les signes cliniques. La sérologie syphilitique est la seule sérologie systématique. Les sérologies toxoplasmose et herpès virus seront réalisées en cas de suspicion diagnostique et avant tout prélèvement oculaire. En l’absence de cause identifiée, nous proposons un bilan paraclinique orienté par les caractéristiques de l’uvéite. Il comporte un typage HLA B27 (uvéite antérieure aiguë unilatérale non granulomateuse), un dosage de l’enzyme de conversion de l’angiotensine, un test IFN-μ release assay (IGRA) et un scanner thoracique (uvéite chronique), une IRM cérébrale associée à une ponction de chambre antérieure avec dosage de l’interleukine 10 (uvéite intermédiaire ou postérieure après 40 ans). La rentabilité d’examens complémentaires non orientés est très faible.
Published: 2017

318. Evaluation of Imaging Strategy to Optimize and Improve Outcome of Transcatheter Aortic Valvular Implantation

Author: Laurent Riou, Adrien Jankowski, Nicolas Piliero, Daniel Fagret, Charlotte Casset, Jean-Louis Quesada, Gilbert Ferretti, Alexis Broisat, Gérald Vanzetto, Bernard Bertrand, Gilles Barone-Rochette, Carole Saunier, Catherine Ghezzi, Mathieu Rodière, Département de cardiologie [CHU de Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Service central de radiologie et d'imagerie médicale, CHU Grenoble-Hôpital Michallon, CIC - Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Radiopharmaceutiques biocliniques (LRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), French alliance clinical trial, French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), and Perret, Pascale
Subjects: Male, medicine.medical_specialty, Transcatheter aortic, Regurgitation (circulation), Kaplan-Meier Estimate, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 030204 cardiovascular system & hematology, Disease-Free Survival, [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, law.invention, Transcatheter Aortic Valve Replacement, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Multidetector Computed Tomography, medicine, Humans, 030212 general & internal medicine, Heart valve, Prospective Studies, Prospective cohort study, Stroke, Aged, Aged, 80 and over, End point, business.industry, Ultrasound, Aortic Valve Stenosis, medicine.disease, 3. Good health, medicine.anatomical_structure, Treatment Outcome, Cardiology, Female, Radiology, Cardiology and Cardiovascular Medicine, business, Echocardiography, Transesophageal
Abstract: International audience; Cardiac computed tomography (CT) provides additional information with ultrasound in the transcatheter heart valve (THV) size selection. However, the influence of these incremental data on outcomes has not been evaluated in a randomized study. A single-center prospective, randomized, and open study was performed. Patients referred for transfemoral transcatheter aortic valve implantation with a balloon-expandable endoprothesis were included. THV size selection was performed using either transthoracic and transesophageal echocardiography data (control group) or ultrasound and CT results (CT group). The primary composite end point included the occurrence of stroke, major vascular complications, and moderate or severe paravalvular aortic regurgitation (PAR) at 1 year. Fifty patients (n = 25 in the control and CT groups) were enrolled. The primary composite end point occurred in 40% and 8% of patients from the control and CT groups, respectively (p = 0.008). The Kaplan-Meier analysis revealed a pejorative association with not performing the CT (p = 0.007). A decrease in the occurrence of PAR was observed in the CT group compared with the control group (PAR 28% vs 4%, p = 0.04; major vascular complications 12% vs 4%, p = 0.6; all-cause death 16% vs. 4%, p = 0.34; no stroke). In conclusion, the use of cardiac CT in addition to ultrasound data in THV size selection reduced the long-term occurrence of cardiovascular events.
Published: 2017

319. C-Reactive Protein on Postoperative Day 1 Is a Reliable Predictor of Pancreas-Specific Complications After Pancreaticoduodenectomy

Author: O. Risse, Coralie Lemoine, Stéphane Berdah, Edouard Girard, Mircea Chirica, Théophile Guilbaud, David Jérémie Birnbaum, Vincent Moutardier, Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), Assistance Publique - Hôpitaux de Marseille (APHM), Département de chirurgie digestive et de l'urgence, CHU Grenoble-Hôpital Michallon, Laboratoire de Biomécanique Appliquée (LBA UMR T24), Aix Marseille Université (AMU)-Université Gustave Eiffel, Laboratoire d'Anatomie des Alpes Françaises (LADAF), CHU Grenoble, Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire [Grenoble] (CHU), Ingénierie Biomédicale et Mécanique des Matériaux (TIMC-IMAG-BioMMat), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), and Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: Adult, Male, medicine.medical_specialty, Abdominal Abscess, Time Factors, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Anastomotic Leak, 030230 surgery, Gastroenterology, Patient Readmission, Pancreaticoduodenectomy, 03 medical and health sciences, Pancreatic Fistula, Young Adult, 0302 clinical medicine, Predictive Value of Tests, Risk Factors, Internal medicine, medicine, Humans, Postoperative Period, Abscess, Pathological, ComputingMilieux_MISCELLANEOUS, Bile leak, Aged, Pancreatic duct, Aged, 80 and over, biology, business.industry, C-reactive protein, Anastomosis, Surgical, Pancreatic Ducts, Middle Aged, medicine.disease, 3. Good health, medicine.anatomical_structure, C-Reactive Protein, ROC Curve, Pancreatic fistula, 030220 oncology & carcinogenesis, biology.protein, Surgery, Female, Pancreas, business
Abstract: Postoperative pancreatic fistula and pancreas-specific complications have a significant influence on patient management and outcomes after pancreatoduodenectomy. The aim of the study was to assess the value of serum C-reactive protein on the postoperative day 1 as early predictor of pancreatic fistula and pancreas-specific complications. Between 2013 and 2016, 110 patients underwent pancreaticoduodenectomy. Clinical, biological, intraoperative, and pathological characteristics were prospectively recorded. Pancreatic fistula was graded according to the International Study Group on Pancreatic Fistula classification. A composite endpoint was defined as pancreas-specific complications including pancreatic fistula, intra-abdominal abscess, postoperative hemorrhage, and bile leak. The diagnostic accuracy of serum C-reactive protein on postoperative day 1 in predicting adverse postoperative outcomes was assessed by ROC curve analysis. Six patients (5%) died and 87 (79%) experienced postoperative complications (pancreatic-specific complications: n = 58 (53%); pancreatic fistula: n = 48 (44%)). A soft pancreatic gland texture, a main pancreatic duct diameter
Published: 2017

320. Solar simulated light exposure alters metabolization and genotoxicity induced by benzo[a]pyrene in human skin explants

Author: von Koschembahr, Anne, Béal, David, Leccia, Marie-Thérèse, Maitre, Anne, Douki, Thierry, Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Département Pluridisciplinaire de Médecine, Dermatologie, CHU Grenoble-Hôpital Michallon, Centre Hospitalier Universitaire [Grenoble] (CHU), Environnement et Prédiction de la Santé des Populations (TIMC-IMAG-EPSP), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
Subjects: [SDV.TOX]Life Sciences [q-bio]/Toxicology, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

321. Prolonged versus standard native E. coli asparaginase therapy in childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma: Final results of the EORTC-CLG randomized phase III trial 58951

Author: Mondelaers, Veerle, Suciu, Stefan, de Moerloose, Barbara, Ferster, Alina, Mazingue, Françoise, Plat, Genevieve, Yakouben, Karima, Uyttebroeck, Anne, Lutz, Patrick, Costa, Vitor, Sirvent, Nicolas, Plouvier, Emmanuel, Munzer, Martine, Poiree, Maryline, Minckes, Odile, Millot, Frédéric, Plantaz, Dominique, Maes, Philip, Hoyoux, Claire, Cavé, Hélène, Rohrlich, Pierre, Bertrand, Yves, Benoit, Yves, Department of Pediatric Hematology-Oncology and Stem Cell Transplantation [Ghent, Belgium], Universiteit Gent = Ghent University [Belgium] (UGENT)-Ghent University Hospital, EORTC Headquarters [Brussels, Belgium], Department of Pediatric Hematology-Oncology [Bruxelles, Belgium], Université libre de Bruxelles (ULB)-Children's University Hospital Queen Fabiola [Bruxelles, Belgium], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Department of Pediatric Hematology- Oncology [Leuven, Belgium], University Hospital Gasthuisberg, Hôpital de Hautepierre [Strasbourg], Department of Pediatrics [Porto, Portugal], Portuguese Oncology Institute, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Service de pédiatrie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Département d'hémato-oncologie pédiatrique [Hôpital American Memorial, Reims], Hôpital American Memorial [Reims], Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Département de pédiatrie, CHU Grenoble-Hôpital Michallon, Service de Pédiatrie [HU Antwerp, Belgium], Antwerp University Hospital [Edegem] (UZA), Service de Pédiatrie [CHR de la Citadelle, Liège, Belgium], Centre Hospitalier Régional de la Citadelle [Liège, Belgium] (CHR de la Citadelle), Unité fonctionnelle de génétique clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Hémopathies Myéloïdes : Cellules Souches, Modèles Pré-Cliniques et Recherche Translationnelle (UMR 1131), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL), European Org Res Treatment Canc, Universiteit Gent = Ghent University (UGENT)-Ghent University Hospital, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), University Hospital Gasthuisberg [Leuven], and Herrada, Anthony
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, MINIMAL RESIDUAL DISEASE, CHILDREN, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.CAN] Life Sciences [q-bio]/Cancer, Medicine and Health Sciences, ONCOLOGY-GROUP, EXPOSURE, ERWINIA-ASPARAGINASE, RISK, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Science & Technology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, INDUCTION THERAPY, CANCER, DEXAMETHASONE, REDUCTION, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Human medicine, Life Sciences & Biomedicine, Hématologie
Abstract: Asparaginase is an essential component of combination chemotherapy for childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma. The value of asparaginase was further addressed in a group of non-very high-risk patients by comparing prolonged (long-asparaginase) versus standard (short-asparaginase) native E. coli asparaginase treatment in a randomized part of the phase III 58951 trial of the European Organization for Research and Treatment of Cancer Children’s Leukemia Group. The main endpoint was disease-free survival. Overall, 1,552 patients were randomly assigned to long-asparaginase (775 patients) or short-asparaginase (777 patients). Patients with grade ≥2 allergy to native E. coli asparaginase were switched to equivalent doses of Erwinia or pegylated E. coli asparaginase. The 8-year disease-free survival rate (±standard error) was 87.0±1.3% in the long-asparaginase group and 84.4±1.4% in the short-asparaginase group (hazard ratio: 0.87; P=0.33) and the 8-year overall survival rate was 92.6±1.0% and 91.3±1.2% respectively (hazard ratio: 0.89; P=0.53). An exploratory analysis suggested that the impact of long-asparaginase was beneficial in the National Cancer Institute standard-risk group with regards to disease-free survival (hazard ratio: 0.70; P=0.057), but far less so with regards to overall survival (hazard ratio: 0.89). The incidences of grade 3-4 infection during consolidation (25.2% versus 14.4%) and late intensification (22.6% versus 15.9%) and the incidence of grade 2-4 allergy were higher in the long-asparaginase arm (30% versus 21%). Prolonged native E. coli asparaginase therapy in consolidation and late intensification for our non-very high-risk patients did not improve overall outcome but led to an increase in infections and allergy., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2017

322. Diagnostic value of stress thallium-201/rest technetium-99m-sestamibi sequential dual isotope high-speed myocardial perfusion imaging for the detection of haemodynamically relevant coronary artery stenosis

Author: Loïc Djaileb, Jean-Louis Quesada, Laurent Riou, Gilles Barone-Rochette, Nicolas Piliero, Jacques Machecourt, Alex Calizzano, Feras Zoreka, Catherine Ghezzi, Gérald Vanzetto, Daniel Fagret, Alexis Broisat, Radiopharmaceutiques biocliniques (LRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Département de cardiologie [CHU de Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), French alliance clinical trial [Paris] (F-CRIN), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Département de médecine Nucléaire [CHU Grenoble-Alpes], Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes), Centre d'Investigation Clinique [Grenoble] (CIC Grenoble ), CHU Grenoble-Hôpital Michallon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Perret, Pascale
Subjects: Male, Fractional flow reserve, 030204 cardiovascular system & hematology, Coronary Angiography, Coronary artery disease, 030218 nuclear medicine & medical imaging, 0302 clinical medicine, Occlusion, fractional flow reserve, Child, Aged, 80 and over, medicine.diagnostic_test, Myocardial Perfusion Imaging, Middle Aged, Fractional Flow Reserve, Myocardial, SPECT, Cardiology, Thallium, Female, Cardiology and Cardiovascular Medicine, Perfusion, Adult, Technetium Tc 99m Sestamibi, medicine.medical_specialty, Adolescent, chemistry.chemical_element, dual isotope, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Sensitivity and Specificity, [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 03 medical and health sciences, Myocardial perfusion imaging, Young Adult, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Rest (music), Aged, business.industry, Coronary Stenosis, medicine.disease, Stenosis, Thallium Radioisotopes, chemistry, Exercise Test, new camera CZT, Radiopharmaceuticals, business
Abstract: International audience; BACKGROUND:The aim of this study was to determine the diagnostic accuracy of stress thallium-201/rest technetium-99m-sestamibi sequential dual-isotope high-speed myocardial perfusion imaging (DI-HS-MPI) against invasively determined fractional flow reserve (FFR).METHODS:Fifty-four consecutive patients prospectively underwent DI-HS-MPI before invasive coronary angiography. Perfusion was scored visually by summed stress score on a patient and coronary territory basis. Significant coronary artery disease (CAD) was defined by the presence of ≥ 90% stenosis/occlusion or fractional flow reserve ≤ 0.80 for coronary stenosis ≥ 50%.RESULTS:FFR was measured in 69 of 162 coronary vessels, with 1.28 ± 0.56 vessels assessed/patient. Sensitivity, specificity, and diagnostic accuracy of MPI for the detection of significant CAD were 92.8%, 69.2%, and 81.4%, on a patient basis, and 83.7%, 90.4%, and 88.8% by coronary territory.CONCLUSIONS:DI-HS-MPI accurately detects functionally significant CAD as defined by using FFR.
Published: 2017

323. Characterization of foreign materials in paraffin-embedded pathological specimens using in situ multi-elemental imaging with laser spectroscopy

Author: Jean-Luc Coll, Julie Charles, Lucie Sancey, Michel D'Incan, Vincent Motto-Ros, Florian Trichard, Philippe Dugourd, Benoit Busser, S. Moncayo, Vincent Bonneterre, Frédéric Pelascini, N. Pinel, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut Lumière Matière [Villeurbanne] (ILM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Universidad Complutense de Madrid [Madrid] (UCM), Ablatom, Laboratoire de Spectrométrie Physique (LSP), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Environnement et Prédiction de la Santé des Populations (TIMC-IMAG-EPSP), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Département d'anatomie et cythologie pathologique, CHU Grenoble-Hôpital Michallon, CRITT Bio-Industrie, Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Institut de Chimie de Strasbourg, Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), and Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: 0301 basic medicine, In situ, Pathology, medicine.medical_specialty, Elemental imaging, Materials science, Tissue imaging, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, medicine, Pseudolymphoma, Humans, Retrospective Studies, Skin, Paraffin Embedding, Foreign-Body Reaction, Lasers, Spectrophotometry, Atomic, Histopathological analysis, Histology, medicine.disease, Paraffin embedded, 3. Good health, Characterization (materials science), 030104 developmental biology, Metals, 030220 oncology & carcinogenesis, Lymph Nodes
Abstract: International audience; Pathologists typically encounter many disparate exogenous materials in clinical specimens during their routine histopathological examinations, especially within the skin, lymph nodes, and lungs. These foreign substances may be free extracellular deposits or induce several clinical abnormalities or histopathological patterns. However, pathologists almost never investigate or report the chemical nature of exogenous metals in clinical specimens due to a lack of convenient and available technologies. In this paper, a novel strategy based on laser-induced breakdown spectroscopy (LIBS) technology is evaluated for in situ multi-elemental tissue imaging. The improved procedures allow visualization of the presence of chemical elements contained within paraffin-embedded specimens of medical interest with elemental images that are stackable with conventional histology images. We selected relevant medical situations for which the associated pathology reports were limited to the presence of lymphohistiocytic and inflammatory cells containing granules (a granuloma and a pseudolymphoma) or to lymph nodes or skin tissues containing pigments or foreign substances. Exogenous elements such as aluminum, titanium, copper, and tungsten were identified and localized within the tissues. The all-optical LIBS elemental imaging instrument that we developed is fully compatible with conventional optical microscopy used for pathology analysis. When combined with routine histopathological analysis, LIBS is a versatile technology that might help pathologists establish or confirm diagnoses for a wide range of medical applications, particularly when the nature of external agents present in tissues needs to be investigated.
Published: 2017

324. Organ preservation for rectal cancer (GRECCAR 2): a prospective, randomised, open-label, multicentre, phase 3 trial

Author: Michel Prudhomme, Igor Sileznieff, Frédéric Marchal, Anne Rullier, Julien Asselineau, Alain Valverde, Denis Pezet, G. Portier, Jean-Jacques Tuech, Bernard Lelong, Eric Rullier, Véronique Vendrely, Bernard Meunier, Jean-Luc Faucheron, Adélaïde Doussau, Michel Rivoire, Quentin Denost, Mehrdad Jafari, Marc Pocard, Philippe Rouanet, Centre d'investigation clinique et d'épidémiologie clinique 7 (CIC-EC7), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut Bergonié - CRLCC Bordeaux-Institut National de la Santé et de la Recherche Médicale (INSERM)-Cancéropôle du Grand Sud-Ouest, Department of Surgical Oncology, Centre Val d'Aurelle, Laboratoire d'éthique médicale et médecine légale (LEM), Université Paris Descartes - Paris 5 (UPD5), Service de chirurgie thoracique cardiaque et vasculaire [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Applications des ultrasons à la thérapie, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Chirurgie Générale et Digestive [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service de Chirurgie Hépatobiliaire et Digestive, Département de chirurgie digestive, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Department of Digestive Surgery, University Medical Hospital, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Groupe Hospitalier Saint-André, Groupe hospitalier Saint-André, Bioingénierie tissulaire (BIOTIS), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Soutien Méthodologique à la Recherche Clinique (USMR), CHU Bordeaux [Bordeaux], Pôle de Santé publique, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Cancéropôle du Grand Sud-Ouest, Service de Chirurgie Hépatobiliaire et Digestive [Rennes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de la Recherche Agronomique (INRA), Service de chirurgie thoracique cardiaque et vasculaire [Rennes] = Thoracic and Cardiovascular Surgery [Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [Rennes], Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Cancéropôle du Grand Sud-Ouest, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: medicine.medical_specialty, Population, 030230 surgery, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Clinical endpoint, medicine, Stage (cooking), Prospective cohort study, education, ComputingMilieux_MISCELLANEOUS, education.field_of_study, business.industry, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, General Medicine, Total mesorectal excision, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Surgery, Clinical trial, 030220 oncology & carcinogenesis, business, Chemoradiotherapy
Abstract: Summary Background Organ preservation is a concept proposed for patients with rectal cancer after a good clinical response to neoadjuvant chemotherapy, to potentially avoid morbidity and side-effects of rectal excision. The objective of this study was to compare local excision and total mesorectal excision in patients with a good response after chemoradiotherapy for lower rectal cancer. Methods We did a prospective, randomised, open-label, multicentre, phase 3 trial at 15 tertiary centres in France that were experts in the treatment of rectal cancer. Patients aged 18 years and older with stage T2T3 lower rectal carcinoma, of maximum size 4 cm, who had a good clinical response to neoadjuvant chemoradiotherapy (residual tumour ≤2 cm) were centrally randomly assigned by the surgeon before surgery to either local excision or total mesorectal excision surgery. Randomisation, which was done via the internet, was not stratified and used permuted blocks of size eight. In the local excision group, a completion total mesorectal excision was required if tumour stage was ypT2–3. The primary endpoint was a composite outcome of death, recurrence, morbidity, and side-effects at 2 years after surgery, to show superiority of local excision over total mesorectal excision in the modified intention-to-treat (ITT) population (expected proportions of patients having at least one event were 25% vs 60% for superiority). This trial was registered with ClinicalTrials.gov, number NCT00427375. Findings From March 1, 2007, to Sept 24, 2012, 186 patients received chemoradiotherapy and were enrolled in the study. 148 good clinical responders were randomly assigned to treatment, three were excluded (because they had metastatic disease, tumour >8 cm from anal verge, and withdrew consent), and 145 were analysed: 74 in the local excision group and 71 in the total mesorectal excision group. In the local excision group, 26 patients had a completion total mesorectal excision. At 2 years in the modified ITT population, one or more events from the composite primary outcome occurred in 41 (56%) of 73 patients in the local excision group and 33 (48%) of 69 in the total mesorectal excision group (odds ratio 1·33, 95% CI 0·62–2·86; p=0·43). In the modified ITT analysis, there was no difference between the groups in all components of the composite outcome, and superiority was not shown for local excision over total mesorectal excision. Interpretation We failed to show superiority of local excision over total mesorectal excision, because many patients in the local excision group received a completion total mesorectal excision that probably increased morbidity and side-effects, and compromised the potential advantages of local excision. Better patient selection to avoid unnecessary completion total mesorectal excision could improve the strategy. Funding National Cancer Institute of France, Sanofi, Roche Pharma.
Published: 2017

325. Admission of tetanus patients to the ICU: a retrospective multicentre study

Author: Carole Schwebel, Jean Marc Tadié, Sébastien Gibot, Nicolas Lerolle, Damien du Cheyron, Nicolas Chudeau, Adel Maamar, Anne Courte, Arnaud W. Thille, Rafael Mahieu, Michael Darmon, Stephane Ehrmann, Ferhat Meziani, Thomas Reydel, Angéline Jamet, Achille Kouatchet, Jean Dellamonica, Gaetan Beduneau, Thibaut Wipf, Christophe Guitton, Steven Grangé, Julien Huntzinger, Julia Champey, Jérémie Lemarié, ATOMycA (CRCINA-ÉQUIPE 6), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Rennes - Faculté de Médecine (UR Médecine), Université de Rennes (UR), Etablissement français du sang [Rennes] (EFS Bretagne), Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Le Mans (CH Le Mans), Service de soins intensifs [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Soins Intensifs [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Réanimation Médicale [CHRU Nancy], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre hospitalier universitaire de Nantes (CHU Nantes), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Clinique de réanimation médicale, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Service de Réanimation Médicale [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Service de Soins Intensifs [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université de Rennes 1 - Faculté de Médecine (UR1 Médecine), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), and Ehrmann, Stephan
Subjects: Pediatrics, medicine.medical_specialty, medicine.medical_treatment, Ventilators, Comorbidity, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, 03 medical and health sciences, 0302 clinical medicine, Mechanical ventilation, Interquartile range, law, Anesthesiology, Medicine, Intensive care unit, 030212 general & internal medicine, Outcome, Aged, Tetanus, business.industry, Mortality rate, Research, lcsh:Medical emergencies. Critical care. Intensive care. First aid, 030208 emergency & critical care medicine, lcsh:RC86-88.9, medicine.disease, Prognosis, Mechanical, 3. Good health, SAPS II, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business, Elderly patient
Abstract: International audience; Background: An extended course of tetanus (up to 6 weeks) requiring ICU admission and protracted mechanical ventilation (MV) may have a significant impact on short-and long-term survival. The subject is noteworthy and deserves to be discussed. Methods: Twenty-two ICUs in France performed tetanus screenings on patients admitted between January 2000 and December 2014. Retrospective data were collected from hospital databases and through the registers of the town hall of the patients. Results: Seventy patients were included in 15 different ICUs. Sixty-three patients suffered from severe or very severe tetanus according to the Ablett classification. The median age was 80 years [interquartile range 73-84], and 86% of patients were women. Ninety per cent of patients (n = 63) required MV for a median of 36 days [26-46], and 66% required administration of a neuromuscular-blocking agent for 23 days [14-29]. A nosocomial infection occurred in 43 patients (61%). ICU and 1-year mortality rates were 14% (n = 10) and 16% (n = 11), respectively. Forty-five per cent of deaths occurred during the first week. Advanced age, a higher SAPS II, any infection, and the use of vasopressors were significantly associated with a lower number of days alive without ventilator support by day 90. Age was the only factor that significantly differed between deceased and survivors at 1 year (83 [81-85] vs. 79 [73-84] years, respectively; p = 0.03). Sixty-one per cent of survivors suffered no impairment to their functional status. Conclusion: In a high-income country, tetanus mainly occurs in healthy elderly women. Despite prolonged MV and extended ICU length of stay, we observed a low 1-year mortality rate and good long-term functional status.
Published: 2017

326. Dissection of a Renal Artery Originating in the Thorax and Coursing Through the Diaphragm: A Complication of Renal Artery Entrapment

Author: Frédéric Thony, Jean-Luc Magne, Mathieu Rodière, Julien Ghelfi, Gilbert Ferretti, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service central de radiologie et d'imagerie médicale, CHU Grenoble-Hôpital Michallon, Departement de Chirurgie Vasculaire et Thoracique, CHU Grenoble, Pôle d'imagerie, and Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble
Subjects: Thorax, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Dissection (medical), 030204 cardiovascular system & hematology, medicine.disease, Diaphragm (structural system), Surgery, 03 medical and health sciences, Entrapment, 0302 clinical medicine, medicine.artery, medicine, Radiology, Nuclear Medicine and imaging, Renal artery, Cardiology and Cardiovascular Medicine, Complication, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2017

327. Characteristics and Outcomes of Patients with Lung Cancer Harboring Multiple Molecular Alterations: Results from the IFCT Study Biomarkers France

Author: Eric Pichon, Annie Wdowik, Jean-Christophe Sabourin, François Guichard, Bénédicte Mastroianni, Nicolas Guibert, Fabrice Barlesi, Alexandra Langlais, Benjamin Besse, Denis Moro-Sibilot, Julien Mazieres, P. Missy, L. Moreau, Antoinette Lemoine, Renaud Descourt, L'Houcine Ouafik, Hervé Lena, Michèle Beau-Faller, Jean Mosser, Jean-Philippe Merlio, Université Fédérale Toulouse Midi-Pyrénées, Oncologie multidisciplinaire et innovations thérapeutiques (OMIT), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Service d'Oncologie Thoracique (BREST - ICH), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de pneumologie [Rennes] = Pneumology [Rennes], CHU Pontchaillou [Rennes], Institut Gustave Roussy (IGR), Laboratoire de Biochimie et de Biologie Moléculaire, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Institut de Génétique et Développement de Rennes (IGDR), Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Département de pathologie [Hôpital Haut Lévêque], Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Laboratoire de Transfert d'Oncologie Biologique [Hôpital Nord - APHM], Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Polyclinique Bordeaux Nord Aquitaine, Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital pasteur [Colmar], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), CHU Rouen, Normandie Université (NU), Microenvironnement et Physiopathologie de la Differenciation, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie et Biostatistique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Département de biologie intégrée, CHU Grenoble-Hôpital Michallon, Service de Pneumologie, Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Université de Toulouse (UT), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Polyclinique Bordeaux Nord Aquitaine (PBNA), Service Pneumologie-Allergologie [CHU Toulouse], Pôle Clinique des Voies respiratoires [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Male, 0301 basic medicine, Oncology, Biomarkers France, Lung Neoplasms, medicine.medical_treatment, Bioinformatics, medicine.disease_cause, NSCLC, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Single mutation, Antineoplastic Combined Chemotherapy Protocols, Anaplastic lymphoma kinase, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, Mutation, Middle Aged, Prognosis, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Female, KRAS, Adult, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Adolescent, EGFR, [SDV.CAN]Life Sciences [q-bio]/Cancer, Adenocarcinoma, Young Adult, 03 medical and health sciences, Multiple mutations, Internal medicine, Biomarkers, Tumor, medicine, Humans, Lung cancer, Gene, Aged, Chemotherapy, Oncogene, business.industry, medicine.disease, 030104 developmental biology, Concomitant, Carcinoma, Large Cell, business, Follow-Up Studies
Abstract: Little is known about the prevalence, prognosis, and response to treatment of advanced NSCLC harboring multiple genomic alterations.The French Biomarkers France database, which includes 17,664 patients, was used. The prevalence of multiple alterations, their associations, their impact on prognosis (overall survival [OS]), and their response to targeted or conventional treatments (progression-free survival [PFS] and objective response rate) were assessed and compared with those of patients harboring single or no mutation.We identified 162 patients (0.9%) with double alterations and three with triple mutations. Multiple molecular alterations preferentially involved KRAS (67.3%), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA) (53.3%), and EGFR (42.4%). Patients with multiple alterations were more likely to be male (56.4%), be never-smokers (25.8 versus 34.7%, p0.001), and exhibit adenocarcinomas (83.6%). OS did not differ between single and multiple alterations. Patients with EGFR/KRAS and EGFR/PIK3CA mutations experienced worse PFS than did patients with only EGFR mutations (7.1 and 7.1 versus 14.9 months, p = 0.02 and 0.002, respectively). Concomitant mutations in patients harboring anaplastic lymphoma receptor tyrosine kinase gene (ALK) rearrangement bore little impact on OS (17.7 versus 20.3 months, p = 0.57) or PFS (10.3 versus 12.1 months, p = 0.93). Patients harboring KRAS mutations plus another alteration had an OS time (13.4 versus 11.2 months, p = 0.28), PFS time (6.4 versus 7.2 months, p = 0.78), and objective response rate under first-line chemotherapy (41.7% versus 37.2%) similar to those of patients harboring KRAS mutations only.With almost 1% of patients harboring multiple alterations, the dogma of mutually exclusive mutations should be reconsidered. Although double mutations do not decrease OS, they do alter PFS under first-line treatment for patients with EGFR mutations. Among limited numbers of patients, therapies targeting the dominant oncogene seem to usually remain active.
Published: 2017

328. Muscle hypertrophy in hypoxia with inflammation is controlled by bromodomain and extra-terminal domain proteins

Author: Nicholas Smithers, Sophie Rousseaux, Christophe Pison, Clovis Chabert, Hervé Dubouchaud, Saadi Khochbin, Uwe Schlattner, Rab K. Prinjha, Rebecca C. Furze, Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), GlaxoSmithKline, Glaxo Smith Kline, Département de médecine aiguë spécialisée, CHU Grenoble-Hôpital Michallon, Fondation 'Agir pour les maladies chroniques', Grenoble, France, Fondation ARC, FRM, Institut National du Cancer (INCa), and ANR-15-CE12-0005,EpiSperm3,Bases moleculaires de la programmation post-méiotique du genome male(2015)
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, lcsh:Medicine, P70-S6 Kinase 1, Inflammation, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Systemic inflammation, Heterocyclic Compounds, 4 or More Rings, Article, Muscle hypertrophy, Histones, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, Muscular Diseases, Protein Domains, Internal medicine, medicine, Animals, Humans, Rats, Wistar, lcsh:Science, Hypoxia, Muscle, Skeletal, Myogenin, Soleus muscle, Multidisciplinary, biology, lcsh:R, Acetylation, Hypertrophy, Pneumonia, Hypoxia (medical), 3. Good health, 030104 developmental biology, Histone, Endocrinology, biology.protein, lcsh:Q, medicine.symptom
Abstract: Some of the Chronic Obstructive Pulmonary Disease (COPD) patients engaged in exercise-based muscle rehabilitation programs are unresponsive. To unravel the respective role of chronic hypoxia and pulmonary inflammation on soleus muscle hypertrophic capacities, we challenged male Wistar rats to repeated lipopolysaccharide instillations, associated or not with a chronic hypoxia exposure. Muscle hypertrophy was initiated by bilateral ablation of soleus agonists 1 week before sacrifice. To understand the role played by the histone acetylation, we also treated our animals with an inhibitor of bromodomains and extra terminal proteins (I-BET) during the week after surgery. Pulmonary inflammation totally inhibited this hypertrophy response under both normoxic and hypoxic conditions (26% lower than control surgery, p
Published: 2017

329. Functional cerebral reorganization of visual scene processing in age-related macular degeneration patients

Author: Peyrin, Carole, Ramanoël, Stephen, Hera, Ruxandra, Chiquet, Christophe, Krainik, Alexandre, Chokron, Sylvie, Laboratoire de Psychologie et NeuroCognition (LPNC ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'Ophtalmologie [Grenoble], Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Centre Hospitalier Universitaire [Grenoble] (CHU), INSERM U836, équipe 5, Neuroimagerie fonctionnelle et perfusion cérébrale, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Neuro-radiologie et IRM, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-CHU Grenoble, Laboratoire Psychologie de la Perception (LPP - UMR 8242), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), ANR-12-JSH2-0002,RECOR,Spécialisation hémisphérique, cartographie rétinotopique et interactions rétino-corticales lors de la perception de scènes(2012), Laboratoire de Psychologie et NeuroCognition (LPNC), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Département de Neuro-radiologie et IRM, and Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble
Subjects: genetic structures, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.PSYC]Cognitive science/Psychology, eye diseases
Abstract: International audience; Age-related macular degeneration (AMD) represents an interesting way to study cortical reorganization after a peripheral lesion of the visual system, as well as the link between cortical activation and visual function. In AMD, the processing of fine details in a visual scene, or high spatial frequencies (HSF), is impaired in patients' residual vision, while the processing of global shapes, or low spatial frequencies (LSF), is relatively well-preserved. The present fMRI study aimed to investigate the residual abilities and functional cerebral reorganization of spatial frequency processing in visual scenes in AMD patients.AMD patients and normally sighted elderly participants performed a categorization task under fMRI, using large black and white photographs of scenes (indoors vs. outdoors, with a visual angle of 24x18 degrees) filtered in LSF, HSF, and non-filtered scenes. The study also explored the effect of luminance contrast on spatial frequency processing. Contrast across scenes was either unmodified, or equalized using a root-mean-square contrast normalization in order to increase contrast in HSF scenes.Results showed that performances were lower for HSF than for NF and LSF scenes, for both AMD patients and controls. However, the selective deficit in the categorization of HSF scenes was more pronounced in AMD patients than in control participants, and was associated with lower activity in the occipital cortex and the parahippocampal place area, a distant cerebral region specialized for scene recognition. Increasing the contrast of HSF scenes improved the processing in the residual vision and spurred activation of the occipital cortex for AMD patients.Therefore, a deficit in processing HSF in scenes exists in AMD patients, in association with an absence of activation in the occipital cortex, but also in a distant scene selective region. Functional brain changes may explain why AMD patients exhibit greater difficulty with details processing even in their residual vision. The deficit can be partially restored by enhancing luminance contrast. These findings may lead to new perspectives for rehabilitation procedures for the residual vision of AMD patients.
Published: 2017

330. Ischemic Gastric Conditioning by Preoperative Arterial Embolization Before Oncologic Esophagectomy: A Single-Center Experience

Author: Sébastien Guigard, Ivan Bricault, Pierre-Yves Brichon, Julien Ghelfi, Bastien Boussat, Christian Sengel, Julien Frandon, Gilbert Ferretti, Service central de radiologie et d'imagerie médicale, CHU Grenoble-Hôpital Michallon, Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de Chirurgie thoracique, CHU Grenoble, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire [Grenoble] (CHU), and Biologie Computationnelle et Mathématique (TIMC-IMAG-BCM)
Subjects: Male, medicine.medical_specialty, Left gastric artery, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Embolization procedure, Anastomotic Leak, Anastomosis, Splenic artery, 03 medical and health sciences, Embolization, 0302 clinical medicine, Postoperative Complications, medicine.artery, Preoperative Care, medicine, Humans, Anastomotic leakage, Radiology, Nuclear Medicine and imaging, Ischemic Preconditioning, Aged, Retrospective Studies, business.industry, Arterial Embolization, Stomach, Middle Aged, Gastric artery, Embolization, Therapeutic, 3. Good health, Surgery, Esophagectomy, Treatment Outcome, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Ischemic conditioning, Radiology, Cardiology and Cardiovascular Medicine, business, Right gastric artery
Abstract: International audience; PURPOSE:Surgical esophagectomy is the gold standard treatment of early-stage esophageal cancer. The procedure is complicated with significant morbidity; the most severe complication being the anastomotic leakage. Anastomotic fistulas are reported in 5-25% of cases and are mainly due to gastric transplant ischemia. Here, we report our experience of ischemic pre-conditioning using preoperative arterial embolization (PreopAE) before esophagectomy.MATERIALS AND METHODS:The medical records of all patients who underwent oncologic esophagectomy from 2008 to 2015 were retrospectively reviewed. Patients were divided into two groups: patients who received PreopAE, and a control group of patients who did not benefit from ischemic pre-conditioning. The target arteries selected for PreopAE were the splenic artery, left gastric artery, and right gastric artery. Evaluation of the results was based on anastomotic leakage, postoperative mortality, technical success of PreopAE, and complications related to the embolization procedure.RESULTS:Forty-six patients underwent oncologic esophagectomy with PreopAE and 13 patients did not receive ischemic conditioning before surgery. Thirty-eight PreopAE were successfully performed (83%), but right gastric artery embolization failed for 8 patients. Anastomotic leakage occurred in 6 PreopAE patients (13%) and in 6 patients (46%) in the control group (p = 0.02). The mortality rate was 2% in the PreopAE group and 23% in the control group (p = 0.03). Eighteen patients suffered from partial splenic infarction after PreopAE, all treated conservatively.CONCLUSION:Preoperative ischemic conditioning by arterial embolization before oncologic esophagectomy seems to be effective in preventing anastomotic leakage.
Published: 2017

331. Prediction of hepatocellular carcinoma recurrence after liver transplantation: Comparison of four explant-based prognostic models

Author: Charlotte E, Costentin, Giuliana, Amaddeo, Thomas, Decaens, Karim, Boudjema, Philippe, Bachellier, Fabrice, Muscari, Ephrem, Salamé, Pierre-Henri, Bernard, Claire, Francoz, Sébastien, Dharancy, Claire, Vanlemmens, Sylvie, Radenne, Jérôme, Dumortier, Marie-Noelle, Hilleret, Olivier, Chazouillères, Georges P, Pageaux, Julien, Calderaro, Alexis, Laurent, Françoise, Roudot-Thoraval, Christophe, Duvoux, Alain, Luciani, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Pôle des Pathologies Digestives Hépatiques et Transplantation [Hôpital Hautepierre-Strasbourg], Hôpital de Hautepierre [Strasbourg], Chirurgie Générale et Digestive [Rangueil], CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Service d'hépatologie, 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), Physiopathologie des Maladies Inflammatoires de l'Intestin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), service d'Hépato-gastro-entérologie, Hospices Civiles de Lyon-Hôpital Edouard Heriault, Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Service d'hépatologie [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Assistance Publique-Hôpitaux de Paris, Department of Pathology, Centre hospitalier universitaire Henri Mondor, F-94000 Créteil, France, Service de chirurgie digestive, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Pôle Recherche Clinique-Santé Publique [Mondor], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), CHU Toulouse [Toulouse]-Hôpital de Rangueil, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz-Université de Franche-Comté (UFC), Service d'hépatologie [Saint-Antoine], CHU Saint-Antoine [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri-Mondor, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Oncology, Adult, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, recurrence, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, medicine.medical_treatment, Kaplan-Meier Estimate, 030230 surgery, Liver transplantation, Milan criteria, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Prognostic models, ComputingMilieux_MISCELLANEOUS, Neoplasm Staging, Retrospective Studies, Hepatology, liver transplantation, business.industry, Liver Neoplasms, explant pathology, Retrospective cohort study, hepatocellular carcinoma, Middle Aged, Models, Theoretical, medicine.disease, Prognosis, Tumor Burden, Hepatocellular carcinoma, Area Under Curve, Cohort, 030211 gastroenterology & hepatology, Neoplasm staging, Female, France, Neoplasm Recurrence, Local, business, Explant culture
Abstract: Aim Discordance between pre-LT imaging and explanted liver findings have been reported after liver transplantation (LT) for hepatocellular carcinoma (HCC), suggesting the need of reassessing the risk of HCC recurrence post-LT. Our aims were to compare pre-LT imaging and explants features and to test the performances of four explant-based predictive models of recurrence in an external cohort. Methods Staging according to pre-LT imaging and explant features were compared. Four explants-based models were retrospectively tested in a cohort of 372 patients transplanted for HCC in 19 French centres between 2003 and 2005. Accuracies of the scores were compared. Results Pre-LT imaging underestimated tumour burden in 83 (22.7%) patients according to Milan criteria. The highest AUCs for prediction of 5-years recurrence were observed in the "Up to seven" (0.7915 [95% CI: 0.7339-0.849]) and Decaens models (0.747 [95% CI: 0.6877-0.806]), with two levels of risk: low (10%) and high (>50%). Chan and Iwatsuki models identified 3 and 4 levels of risk, but had lower AUCs (0.68 and 0.70) respectively. Accuracy of the "Up to seven" model was superior to the Decaens model (P=.034), which was superior to the Chan model (P=.0041) but not to the Iwatsuki model (P=.17). Conclusion Pre-LT imaging underestimates tumour burden, and prediction of recurrence should be reassessed after LT. The explant-based "Up to seven" and Decaens models provided the best accuracy for prediction of 5-year recurrence, identifying only two levels of risk. New models are needed to further refine the prediction of recurrence after LT.
Published: 2017

332. Menopause Is Associated with Accelerated Lung Function Decline

Author: Sandra Suske, Jesús Martínez-Moratalla Rovira, Karl A. Franklin, Steinar Hustad, Francisco Gómez Real, Bénédicte Leynaert, Kai Triebner, Cecilie Svanes, Nicole Probst-Hensch, Deborah Jarvis, Isabelle Pin, Chantal Raherison, Eva Lindberg, Bryndis Benediktsdottir, Bobette Matulonga, José Luis Sánchez-Ramos, Luca Puggini, Vivi Schlünssen, Ane Johannessen, Mathias Holm, Shyamali C. Dharmage, Pascal Demoly, Joachim Heinrich, Rain Jögi, José Antonio Gullón Blanco, Jordi Sunyer, Judith Garcia-Aymerich, Nerea Muniozguren Agirre, Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Centre d'Investigation Clinique [Grenoble] (CIC Grenoble), Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Michallon, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Grenoble] (CIC Grenoble ), CHU Grenoble-Hôpital Michallon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Medical Research Council (MRC)
Subjects: SYSTEMIC INFLAMMATION, Aging, Respiratory System, Vital Capacity, Physiology, menopause, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Pulmonary function testing, 0302 clinical medicine, Forced Expiratory Volume, Longitudinal Studies, 030212 general & internal medicine, Lung, media_common, education.field_of_study, medicine.diagnostic_test, Age Factors, 11 Medical And Health Sciences, Middle Aged, Respiratory Function Tests, 3. Good health, Europe, Menopause, RESPIRATORY SYMPTOMS, ESTROGEN, medicine.anatomical_structure, POSTMENOPAUSAL WOMEN, Female, HEALTH, MENSTRUAL-CYCLE, Life Sciences & Biomedicine, TRANSITION, Adult, Pulmonary and Respiratory Medicine, Spirometry, medicine.medical_specialty, media_common.quotation_subject, Population, sex hormones, 03 medical and health sciences, FEV1/FVC ratio, Critical Care Medicine, General & Internal Medicine, Internal medicine, Journal Article, medicine, latent class analysis, Humans, education, Menstrual cycle, Asthma, Science & Technology, business.industry, lung function decline, PULMONARY-FUNCTION, medicine.disease, Endocrinology, 030228 respiratory system, reproductive aging, ASTHMA, SEX-HORMONES, business
Abstract: RATIONALE: Menopause is associated with changes in sex hormones, which affect immunity, inflammation, and osteoporosis and may impair lung function. Lung function decline has not previously been investigated in relation to menopause. OBJECTIVES: To study whether lung function decline, assessed by forced vital capacity and forced expiratory volume in one second, is accelerated in women who undergo menopause. METHODS: The population-based longitudinal European Community Respiratory Health Survey provided serum samples, spirometry and questionnaire data about respiratory and reproductive health from three study waves (N=1438). We measured follicle stimulating hormone and luteinizing hormone and added information on menstrual patterns, to determine menopausal status using latent class analysis. Associations with lung function decline were investigated using linear mixed effects models, adjusting for age, height, weight, packyears, current smoking, age at completed full-time education, spirometer and including study center as random effect. MEASUREMENTS AND MAIN RESULTS: Menopausal status was associated with accelerated lung function decline. The adjusted mean forced vital capacity decline was increased by -10.2 ml/yr (95% Confidence interval -13.1 to -7.2) in transitional women and -12.5 ml/yr (-16.2 to -8.9) in postmenopausal women, compared to women menstruating regularly. The adjusted mean forced expiratory volume in one second decline increased by -3.8 ml/yr (-6.3 to -2.9) in transitional women and -5.2 ml/yr (-8.3 to -2.0) in postmenopausal women. CONCLUSIONS: Lung function declined more rapidly among transitional and postmenopausal women, in particular for forced vital capacity, beyond the expected age change. Clinicians should be aware that respiratory health often deteriorates during reproductive aging.
Published: 2017

333. Partial nephrectomy versus ablative therapy for the treatment of renal tumors in an imperative setting

Author: François-Xavier Nouhaud, Idir Ouzaid, Karim Bensalah, Jérôme Rigaud, Laurent Salomon, Christian Sengel, Y. Grassano, Pierre Bigot, François Cornelis, P. Gimel, Nathalie Rioux-Leclercq, Gregory Verhoest, Quentin-Côme Le Clerc, C. Lanchon, Arnaud Mejean, Jean-Christophe Bernhard, Jean-Luc Descotes, Philippe Paparel, Romain Boissier, V. Comat, Nicolas Grenier, Laurence Albiges, Valentin Arnoux, Alexandra Masson-Lecomte, Morgan Rouprêt, Thomas Bodin, Jean-Alexandre Long, Centre Hospitalier Universitaire [Grenoble] (CHU), Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'urologie, andrologie et transplantation rénale, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'urologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), 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 ), Oncologie génito-urinaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre d'Urologie Prado Louvain [Marseille], UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Chirurgie urologique et transplantation rénale [Hôpital de la Conception - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Polyclinique Médipôle Saint-Roch [Cabestany], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Henri Mondor [Créteil], Imagerie moléculaire et fonctionnelle: de la physiologie à la thérapie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Centre National de la Recherche Scientifique (CNRS), Modélisation Mathématique pour l'Oncologie (MONC), Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), CHU Bordeaux [Bordeaux], Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'urologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service central de radiologie et d'imagerie médicale, CHU Grenoble-Hôpital Michallon, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pontchaillou [Rennes], Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Henri Mondor, Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Institut Bergonié [Bordeaux], Service d'Urologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Nephrology, Ablation Techniques, Male, Percutaneous, Radiofrequency ablation, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Comorbidity, Kidney, Cryosurgery, Nephrectomy, law.invention, Neoplasms, Multiple Primary, 0302 clinical medicine, Postoperative Complications, Robotic Surgical Procedures, law, Partial nephrectomy, Cryoablation, Middle Aged, Kidney Neoplasms, 3. Good health, Tumor Burden, Treatment Outcome, Renal cancer, 030220 oncology & carcinogenesis, Catheter Ablation, Female, Kidney Diseases, Glomerular Filtration Rate, medicine.medical_specialty, Urology, Renal function, Imperative indication, Disease-Free Survival, Congenital Abnormalities, 03 medical and health sciences, Internal medicine, medicine, Humans, Blood Transfusion, Renal Insufficiency, Chronic, Carcinoma, Renal Cell, Dialysis, Aged, Retrospective Studies, business.industry, Nephrons, Length of Stay, medicine.disease, Surgery, Radiofrequency, Multivariate Analysis, Laparoscopy, business, Organ Sparing Treatments, Kidney disease
Abstract: International audience; Purpose - To compare partial nephrectomy (PN) and percutaneous ablative therapy (AT) for renal tumor in imperative indication of nephron-sparing technique (NST). Materials and methods - Between 2000 and 2015, 284 consecutive patients with a kidney tumor in an imperative indication of NST were retrospectively included in a multicenter study. PN [open (n = 146), laparoscopic (n = 9), or robotic approach (n = 17)] and AT [radiofrequency ablation (n = 104) or cryoablation (n = 8)] were performed for solitary kidney (n = 146), bilateral tumor (n = 78), or chronic kidney disease (CKD) (n = 60). Results - Patients in the PN group had larger tumors and a higher RENAL score. There were no differences between the two groups with respect to age, reasons for imperative indication, and preoperative eGFR. Patients in the AT group had a higher ASA and CCI. PN had worse outcomes than AT in terms of transfusion rate, length of stay, and complication rate. Local radiological recurrence-free survival was better for PN, but metastatic recurrence was similar. Percentage of eGFR decrease was similar in the two groups. Temporary or permanent dialysis was not significantly different. On multivariate analysis, PN and AT had a similar eGFR change when adjusted for tumor complexity, reason of imperative indication and CCI. Conclusion - In imperative indication of nephron-sparing treatment for a kidney tumor, either PN or AT can be proposed. PN offers the ability to manage larger and more complex tumors while providing a better local control and a similar renal function loss.
Published: 2017

334. Anaemia as an independent key risk factor for major haemorrhage in patients treated with vitamin K antagonists: Results of the SCORE prospective cohort

Author: Yoann Gaboreau, Pierre Albaladejo, Nora Zenati, Gilles Pernod, Jean Luc Bosson, Cynthia Brousseau Provencher, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Techniques pour l'Evaluation et la Modélisation des Actions de la Santé (TIMC-IMAG-ThEMAS), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'anesthésie-réanimation, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, CHU Grenoble, and GIRC Thrombose
Subjects: Male, medicine.medical_specialty, Vitamin K, medicine.drug_class, Anemia, Hemorrhage, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, In patient, 030212 general & internal medicine, Prospective Studies, Risk factor, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, business.industry, Incidence (epidemiology), Incidence, Anticoagulants, Hematology, Vitamin K antagonist, Middle Aged, medicine.disease, Confidence interval, 3. Good health, Surgery, Female, France, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Cohort study
Abstract: Risk scores for the prediction of haemorrhage are poorly predictive of major bleeding. The aim of this study was to refine the estimation of bleeding risk by identifying one or several parameters of prognostic significance among these algorithms.The SCORE study was a prospective, multicentre cohort study conducted in France in 2009-2010. Patients were eligible if they had received vitamin K antagonist (VKA) for any therapeutic indication for at least 3months. The primary outcome was the occurrence of major bleeding at 1-year follow-up.In total, 962 patients were included in this study and evaluated at 1year. The incidence of major bleeding at 1-year follow-up (Kaplan-Meier method) was 2.9% [95% confidence interval (CI) 1.9-4.2]. The rate of major bleeding was 8.2% (95 CI 3.4-16.2) per year in patients classified as high risk by at least four scores. In a multivariate Cox analysis, of the risk factors for the different scores, only anaemia100g/l at inclusion was strongly associated with risk of major bleeding (hazard ratio 6.1, 95% CI 2.7-13.8, P0.0001). Through an induction tree analysis performed to identify a common parameter in the majority of scores, anaemia was found to be the main predictor of correct classification as high risk by at least four scores (55% of patients classified as high risk by at least four scores vs 3.3% in the absence of anaemia).Anaemia with haemoglobin100g/l is the most important predictor of high risk of bleeding in patients treated with VKA.
Published: 2017

335. Computer assisted electromagnetic navigation improves accuracy in computed tomography guided interventions: A prospective randomized clinical trial

Author: Anne-Sophie Silvent, Julien Frandon, Ivan Bricault, Maud Medici, Alexandre Moreau-Gaudry, Emilie Chipon, Pierre M. Durand, ZOPPIS, Catherine, Centre Hospitalier Universitaire [Grenoble] (CHU), Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre d'Investigation Clinique [Grenoble] (CIC Grenoble ), CHU Grenoble-Hôpital Michallon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), SIC, Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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), CIC - Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), and VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)
Subjects: Electromagnetics, Percutaneous, [SDV]Life Sciences [q-bio], Biopsy, lcsh:Medicine, Computed tomography, 030218 nuclear medicine & medical imaging, law.invention, Diagnostic Radiology, 0302 clinical medicine, Randomized controlled trial, Electricity, law, Ultrasound Imaging, Medicine and Health Sciences, Prospective Studies, lcsh:Science, Tomography, Multidisciplinary, medicine.diagnostic_test, Needle holder, Radiology and Imaging, Physics, Navigation, 3. Good health, [SDV] Life Sciences [q-bio], Professions, Research Design, 030220 oncology & carcinogenesis, Physical Sciences, Needle placement, Engineering and Technology, Radiology, Research Article, medicine.medical_specialty, Drug Research and Development, Imaging Techniques, Clinical Research Design, Neuroimaging, Surgical and Invasive Medical Procedures, Research and Analysis Methods, 03 medical and health sciences, Electromagnetic Fields, Diagnostic Medicine, Radiologists, medicine, Humans, Clinical Trials, Pharmacology, business.industry, lcsh:R, Navigation system, Biology and Life Sciences, Randomized Controlled Trials, Computed Axial Tomography, People and Places, lcsh:Q, Population Groupings, Adverse Events, Clinical Medicine, business, Tomography, X-Ray Computed, Neuroscience
Abstract: Purpose To assess the accuracy and usability of an electromagnetic navigation system designed to assist Computed Tomography (CT) guided interventions. Materials and methods 120 patients requiring a percutaneous CT intervention (drainage, biopsy, tumor ablation, infiltration, sympathicolysis) were included in this prospective randomized trial. Nineteen radiologists participated. Conventional procedures (CT group) were compared with procedures assisted by a navigation system prototype using an electromagnetic localizer to track the position and orientation of a needle holder (NAV group). The navigation system displays the needle path in real-time on 2D reconstructed CT images extracted from the 3D CT volume. The regional ethics committee approved this study and all patients gave written informed consent. The main outcome was the distance between the planned trajectory and the achieved needle trajectory calculated from the initial needle placement. Results 120 patients were analyzable in intention-to-treat (NAV: 60; CT: 60). Accuracy improved when the navigation system was used: distance error (in millimeters: median[P25%; P75%]) with NAV = 4.1[2.7; 9.1], vs. with CT = 8.9[4.9; 15.1] (p
Published: 2017

336. Molecular Classification of Hepatocellular Adenoma Associates With Risk Factors, Bleeding, and Malignant Transformation

Author: Nault , Jean-Charles, Couchy , Gabrielle, Balabaud , Charles, Morcrette , Guillaume, Caruso , Stefano, Blanc , Jean-Frederic, Bacq , Yannick, Calderaro , Julien, Paradis , Valérie, Ramos , Jeanne, Scoazec , Jean-Yves, Gnemmi , Viviane, Sturm , Nathalie, Guettier , Catherine, Fabre , Monique, Savier , Eric, Chiche , Laurence, Labrune , Philippe, Selves , Janick, Wendum , Dominique, Pilati , Camilla, Laurent , Alexis, De Muret , Anne, Le Bail , Brigitte, Rebouissou , Sandra, Imbeaud , Sandrine, Investigators , GENTHEP, Bioulac-Sage , Paulette, Letouzé , Eric, Zucman-Rossi , Jessica, Génomique Fonctionnelle des Tumeurs Solides ( U1162 ), Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Jean Verdier, Université Paris 13 ( UP13 ), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], CHU Trousseau [APHP]-Centre Hospitalier Régional Universitaire de Tours ( CHRU TOURS ), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), 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 ), Service d'Anatomo-Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy ( IGR ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc) - U1172 ( JPArc ), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département d'anatomie et cythologie pathologique, CHU Grenoble-Hôpital Michallon, Hôpital Paul Brousse, Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse, Hôpital Bicêtre, Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AP-HP Hôpital Paul Brousse, Service d'anatomie pathologique [CHU Necker], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Service de chirurgie digestive et hépato-bilio-pancréatique [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Hôpital Antoine Béclère, Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP), Thérapie génique, Génomique et Epigénomique ( U 1169 ), Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ), Institut Universitaire du Cancer de Toulouse - Oncopole ( IUCT Oncopole - UMR 1037 ), Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Anatomie Pathologique [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Service de chirurgie digestive, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor, Service d'Anatomopathologie [Tours], CHRU Tours-CHU Trousseau [APHP], Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service d'oncologie médicale [CHU HEGP], and Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP )
Subjects: Benign, Tumor Progression, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, HCC, SHH
Abstract: International audience; BACKGROUND & AIMS:Hepatocellular adenomas (HCAs) are benign liver tumors that can be assigned to molecular subtypes based on inactivating mutations in hepatocyte nuclear factor 1A, activating mutations in β-catenin, or activation of inflammatory signaling pathways. We aimed to update the classification system for HCA and associate the subtypes with disease risk factors and complications.METHODS:We analyzed expression levels of 20 genes and sequenced exon regions of 8 genes (HNF1A, IL6ST, CTNNB1, FRK, STAT3, GNAS, JAK1, and TERT) in 607 samples of 533 HCAs from 411 patients, collected from 28 centers mainly in France from 2000 and 2014. We performed gene expression profile, RNA sequence, whole-exome and genome sequence, and immunohistochemical analyses of select samples. Molecular data were associated with risk factors, histopathology, bleeding, and malignant transformation.RESULTS:Symptomatic bleeding occurred in 14% of the patients (85% of cases were female, median age, 38 years); 7% of the nodules were borderline between HCA and hepatocellular carcinoma, and 3% of patients developed hepatocellular carcinoma from HCA. Based on molecular features, we classified HCA into 8 subgroups. One new subgroup, composed of previously unclassified HCA, represented 4% of HCAs overall and was associated with obesity and bleeding. These tumors were characterized by activation of sonic hedgehog signaling, due to focal deletions that fuse the promoter of INHBE with GLI1. Analysis of genetic heterogeneity among multiple HCAs, from different patients, revealed a molecular subtype field effect; multiple tumors had different mutations that deregulated similar pathways. Specific molecular subtypes of HCA associated with various HCA risk factors, including imbalances in estrogen or androgen hormones. Specific molecular subgroup of HCA with β-catenin and sonic hedgehog activation associated with malignant transformation and bleeding, respectively.CONCLUSIONS:Using sequencing and gene expression analyses, we identified a subgroup of HCA characterized by fusion of the INHBE and GLI1 genes and activation of sonic hedgehog pathway. Molecular subtypes of HCAs associated with different patients' risk factors for HCA, disease progression, and pathology features of tumors. This classification system might be used to select treatment strategies for patients with HCA.
Published: 2017

337. Pancreaticobiliary Maljunctions in European Patients with Bile Duct Cysts: Results of the Multicenter Study of the French Surgical Association (AFC)

Author: Ragot E., Mabrut J. -Y., Ouaissi M., Sauvanet A., Dokmak S., Nuzzo G., Halkic N., Dubois R., Letoublon C., Cherqui D., Azoulay D., Irtan S., Boudjema K., Pruvot F. -R., Gigot J. -F., Kianmanesh R., Adham M., Doussot A., Branchereau S., Ayav A., Balladur P., Adam R., Troisi R. I., Regimbeau Jean M. -A., Majno P., Sommacale D., Bouzid C., Falconi M., Service de chirurgie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de chirurgie digestive, Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de chirurgie hepato-pancreato-biliaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Département de chirurgie digestive et de l'urgence, CHU Grenoble-Hôpital Michallon, Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Est (UPE), Service de Chirurgie Digestive Hépato-Billiaire [Henri Mondor], 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de neurochirurgie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de Chirurgie Hépatobiliaire et Digestive [Rennes] = Hepatobiliary and Digestive Surgery [Rennes], CHU Pontchaillou [Rennes], 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), Foie, métabolismes et cancer, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Chirurgie digestive et transplantation [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Espace éthique hospitalier et universitaire de Lille - EEHU, Ragot, E., Mabrut, J. -Y., Ouaissi, M., Sauvanet, A., Dokmak, S., Nuzzo, G., Halkic, N., Dubois, R., Letoublon, C., Cherqui, D., Azoulay, D., Irtan, S., Boudjema, K., Pruvot, F. -R., Gigot, J. -F., Kianmanesh, R., Adham, M., Doussot, A., Branchereau, S., Ayav, A., Balladur, P., Adam, R., Troisi, R. I., Regimbeau Jean, M. -A., Majno, P., Sommacale, D., Bouzid, C., Falconi, M., Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Beaujon, Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre de Recherches en Oncologie biologique et Oncopharmacologie ( CRO2 ), Aix Marseille Université ( AMU ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AP-HP Hôpital Paul Brousse, Université Paris-Est ( UPE ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de Chirurgie Hépatobiliaire et Digestive, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ) -Espace éthique hospitalier et universitaire de Lille - EEHU, Working Group of the French Surgical Association, Troisi, R.I., Regimbeau Jean, M.A., Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Paul Brousse, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]
Subjects: Male, Gastroenterology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Prevalence, Medicine, Cyst, Child, Aged, 80 and over, education.field_of_study, Bile duct, Incidence, Middle Aged, 3. Good health, medicine.anatomical_structure, Biliary Tract Neoplasms, Biliary tract, 030220 oncology & carcinogenesis, Child, Preschool, Choledochal Cyst, Amylases, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 030211 gastroenterology & hepatology, Female, France, Adult, medicine.medical_specialty, Adolescent, Population, Intrahepatic bile ducts, chemical and pharmacologic phenomena, [SDV.CAN]Life Sciences [q-bio]/Cancer, Congenital Abnormalities, 03 medical and health sciences, Young Adult, Predictive Value of Tests, Internal medicine, Carcinoma, Humans, education, Aged, Common Bile Duct, business.industry, fungi, Pancreatic Ducts, Cancer, Infant, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Lipase, Amylases/metabolism, Biliary Tract Neoplasms/complications, Biliary Tract Neoplasms/epidemiology, Choledochal Cyst/complications, Choledochal Cyst/enzymology, Choledochal Cyst/epidemiology, Common Bile Duct/abnormalities, Congenital Abnormalities/diagnosis, Congenital Abnormalities/epidemiology, Lipase/metabolism, Pancreatic Ducts/abnormalities, medicine.disease, Pancreatic juice, Surgery, business
Abstract: Background: Pancreaticobiliary maljunctions (PBMs) are congenital anomalies of the junction between pancreatic and bile ducts, frequently associated with bile duct cyst (BDC). BDC is congenital biliary tree diseases that are characterized by distinctive dilatation types of the extra- and/or intrahepatic bile ducts. Todani’s types I and IVa, in which dilatation involves principally the main bile duct, are the most frequent. PBM induces pancreatic juice reflux into the biliary tract that is supposed to be one of the main factors of biliary cancer degeneration, although the diagnostic criteria of PBM that can be either morphological and/or functional are not well defined especially in Western series. Objective: The aim of this study was to assess the relative prevalence of PBM in BDC in a large European multicenter study, to analyze the characteristics of PBM and try to propose diagnostic criteria of PBMs based on morphological and/or functional criteria and define the positive, negative predictive values, sensibility and specificity of either criteria. Results: From 1975 to 2012, 263 patients with BDC were analyzed. Among them, 190 (72.2%) were considered to present PBM. Types I and IVa had a similar rate of PBM association. According to the “AFC classification,” 57.2% had a C–P type, 34.5% a P–C type and 8.3% a complex type (“anse-de-seau”). The median length of the common channel in patients with PBM was 15.8±6.8mm (range 5–40mm). The median intrabiliary amylase and lipase levels were 65,249 and 172,104UI/L, respectively. For the diagnostic of PBM, a common channel length of more than 8mm and an intrabiliary amylase level superior to 8000UI/L were associated with a predictive positive value and a specificity of more than 90%. Synchronous biliary cancer had an incidence of 8.7% in all patients with BDC and PBM 11.1% in adults. Compared to type IV, the type I BDC was associated with statistically more cancer patients in the presence of PBM. Conclusions: Characteristics of PBM associated with BDC in Western population are quite close to reported Eastern series. The results suggest considering both the intrabiliary value of amylase >8000UI/L and a length of a common channel >8mm as appropriate values for positive diagnosis of PBM.
Published: 2017

338. Intensité des soins lors des exacerbations et des complications des pathologies respiratoires chroniques

Author: Sakhri, L., Saint-Raymond, C., Quetant, S., Pison, C., Lagrange, E., Hamidfar Roy, R., Janssens, J.-P., Maindet-Dominici, C., Garrouste-Orgeas, M., Levy-Soussan, M., Terzi, N., Toffart, C., CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Département de médecine aiguë spécialisée, CHU Grenoble-Hôpital Michallon, Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Hypoxie et physiopathologies cardiovasculaire et respiratoire, and Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Fibrose pulmonaire idiopathique, [SDV]Life Sciences [q-bio], Sclérose latérale amyotrophique, Bronchopneumopathie chronique obstructive, Soins palliatifs, Cancer bronchopulmonaire, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; The issue of intensive and palliative care in patients with chronic disease frequently arises. This review aims to describe the prognostic factors of chronic respiratory diseases in stable and in acute situations in order to improve the management of these complex situations. The various laws on patients’ rights provide a legal framework and define the concept of unreasonable obstinacy. For patients with chronic obstructive pulmonary disease, the most robust decision factors are good knowledge of the respiratory disease, the comorbidities, the history of previous exacerbations and patient preferences. In the case of idiopathic pulmonary fibrosis, it is necessary to know if there is a prospect of transplantation and to assess the reversibility of the respiratory distress. In the case of amyotrophic lateral sclerosis, treatment decisions depend on the presence of advance directives about the use of intubation and tracheostomy. For lung cancer patients, general condition, cancer history and the tumor treatment plan are important factors. A multidisciplinary discussion that takes into account the patient's medical history, wishes and the current state of knowledge permits the taking of a coherent decision.
Published: 2017

339. Population pharmacokinetics of micafungin in ICU patients with sepsis and mechanical ventilation

Author: Pierre Emmanuel Charles, Fabrice Bruneel, Samir Jaber, Joel Cousson, Muriel Cornet, Arnaud Foucrier, Jean-Louis Trouillet, Maité Garrouste-Orgeas, Thomas Le Saux, Vincent Jullien, Martin Cour, Ferhat Meziani, Elie Azoulay, Stéphane Ruckly, Michael Darmon, Carole Schwebel, Jean-François Timsit, Bertrand Souweine, Adeline Paris, Vincent Das, Bernard Allaouchiche, Jean-Pierre Gangneux, Kadda Klouche, Jean-Christophe Navellou, Didier Gruson, Michel Wolff, 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), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Réanimation Médicale [Grenoble], Hôpital Michallon-CHU Grenoble, Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Département d'anesthésie-réanimation[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de réanimation [CH Versailles], Centre Hospitalier de Versailles André Mignot (CHV), Continental Automotive France [Toulouse], Service de réanimation médicale, Centre Hospitalier Universitaire de Reims (CHU Reims), Département d'Endocrinologie et Nutrition (LOUVAIN - Endocrino), Université Catholique de Louvain = Catholic University of Louvain (UCL), CSE, Centre européen de sociologie et de science politique (CESSP), Université Paris 1 Panthéon-Sorbonne (UP1)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie pronostique des cancers et affections graves, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Réanimation médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Reanimation Médicale et Infectieuse [Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bichat-Claude Bernard, Service de Réanimation, Hospices Civils de Lyon (HCL)-Hôpital E. Herriot, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Space Science Institute [Boulder] (SSI), Unité de Soins Intensifs et de Maladies Infectieuses, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], University of Grenoble 1/Albert Michallon university hospital, Astellas company, Génétique, pharmacologie et physiopathologie des maladies cardiovasculaires [CHU Pitié-Salpétriêre], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Grenoble-Hôpital Michallon, École normale supérieure - Paris (ENS-PSL), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Strasbourg, CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), 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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Epilepsies de l'Enfant et Plasticité Cérébrale ( U1129 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris Descartes - Paris 5 ( UPD5 ), Hopital Saint Louis Paris, CHU Saint Louis [APHP], Service de Réanimation Médicale, CHU Grenoble-Hôpital Albert Michallon, École normale supérieure - Paris ( ENS Paris ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Thérapeutique Recombinante Expérimentale ( TIMC-IMAG-THEREX ), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Laboratoire Microorganismes : Génome et Environnement ( LMGE ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Centre National de la Recherche Scientifique ( CNRS ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ), Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Gui de Chauliac, 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 ), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition ( ICAN ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP], réanimation chirurgicale, CH Versailles, Ministère de la santé, Continental Automotive France SA, Centre Hospitalier Universitaire de Reims ( CHU Reims ), Département d'Endocrinologie et Nutrition ( LOUVAIN - Endocrino ), Université Catholique de Louvain ( UCL ), Centre européen de sociologie et de science politique ( CESSP ), Université Panthéon-Sorbonne ( UP1 ) -École des hautes études en sciences sociales ( EHESS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Panthéon-Sorbonne ( UP1 ) -École des hautes études en sciences sociales ( EHESS ) -Centre National de la Recherche Scientifique ( CNRS ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bichat-Claude Bernard, Hospices Civils de Lyon ( HCL ) -Hôpital E. Herriot, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut de recherche, santé, environnement et travail ( Irset ), Université d'Angers ( UA ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -École des Hautes Études en Santé Publique [EHESP] ( EHESP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) -Université des Antilles ( UA ), Space Science Institute [Boulder] ( SSI ), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), and Cornet, Muriel
Subjects: Male, 0301 basic medicine, Antifungal Agents, Candida parapsilosis, 030226 pharmacology & pharmacy, Gastroenterology, Plasma, Echinocandins, 0302 clinical medicine, Caspofungin, Medicine, Pharmacology (medical), Candida albicans, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Candida, Aged, 80 and over, biology, Middle Aged, 3. Good health, Intensive Care Units, Infectious Diseases, Anesthesia, Female, SOFA score, Monte Carlo Method, medicine.drug, Adult, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Microbial Sensitivity Tests, Lipopeptides, 03 medical and health sciences, Pharmacokinetics, Internal medicine, Humans, Intensive care unit, Healthy volunteers, Aged, Pharmacology, Candida glabrata, business.industry, Adult patients, Micafungin, Candidemia, biology.organism_classification, [SDV.MP.MYC] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Respiration, Artificial, NONMEM, Pharmacodynamics, Critically-ill patients, business
Abstract: International audience; Objectives: To identify the factors associated with the interindividual pharmacokinetic (PK) variability of micafungin and to evaluate the probability of reaching the previously determined PK/pharmacodynamic efficacy thresholds (AUC/MIC >5000 for non-parapsilosis Candida sp. and ≥285 for Candida parapsilosis) with the recommended 100 mg daily dose in ICU patients with sepsis and mechanical ventilation.Methods: One hundred patients were included and 436 concentrations were available for PK analysis performed with NONMEM software. PTA was determined by Monte Carlo simulations.Results: Micafungin obeyed a two-compartment model with first-order elimination from the central compartment. Mean parameter estimates (percentage interindividual variability) were 1.34 L/h (34%) for clearance (CL), 11.80 L (38%) and 7.68 L (39%) for central (Vc) and peripheral (Vp) distribution volumes, respectively, and 4.67 L/h (37%) for distribution clearance. CL, Vc and Vp increased by 14% when the albumin level was ≤25 g/L and CL decreased by 25% when SOFA score was ≥10. Body weight was related to CL, Vc and Vp by allometric models. PTA was ≥90% in Candida albicans and Candida glabrata infections, except when the MIC was ≥0.015 mg/L, and ranged between 0% and 40% for C. parapsilosis infections with MIC ≥0.5 mg/L.Conclusions: A possible increase in the dose should be evaluated for infections due to C. parapsilosis and for infections due to C. albicans and C. glabrata with MICs ≥0.015 mg/L.
Published: 2017

340. Rye polyphenols and the metabolism of n-3 fatty acids in rats: a dose dependent fatty fish-like effect

Author: Fayçal Ounnas, Pedro Mena, Michel de Lorgeril, François Laporte, Christine Demeilliers, Patricia Salen, Daniele Del Rio, Furio Brighenti, Luca Calani, Hamant, Sarah, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Département de biologie intégrée, CHU Grenoble-Hôpital Michallon, Università degli studi di Parma = University of Parma (UNIPR), Environnement et Prédiction de la Santé des Populations (TIMC-IMAG-EPSP), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), and University of Parma = Università degli studi di Parma [Parme, Italie]
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], 030209 endocrinology & metabolism, Biology, Gut flora, Article, 03 medical and health sciences, Fatty fish, 0302 clinical medicine, Fatty Acids, Omega-3, Animals, N-3 fatty acids, 14. Life underwater, Food science, 2. Zero hunger, chemistry.chemical_classification, 030109 nutrition & dietetics, Multidisciplinary, Overfishing, Secale, Polyphenols, Fatty acid, Metabolism, biology.organism_classification, Diet, Gastrointestinal Microbiome, Rats, [SDV] Life Sciences [q-bio], Liver, chemistry, Biochemistry, Polyphenol, lipids (amino acids, peptides, and proteins), Composition (visual arts)
Abstract: As long-chain fatty acids (LCFA) of the n-3 series are critically important for human health, fish consumption has considerably increased in recent decades, resulting in overfishing to respond to the worldwide demand, to an extent that is not sustainable for consumers’ health, fisheries economy, and marine ecology. In a recent study, it has been shown that whole rye (WR) consumption improves blood and liver n-3 LCFA levels and gut microbiota composition in rats compared to refined rye. The present work demonstrates that specific colonic polyphenol metabolites may dose dependently stimulate the synthesis of n-3 LCFA, possibly through their microbial and hepatic metabolites in rats. The intake of plant n-3 alpha-linolenic acid and WR results in a sort of fatty fish-like effect, demonstrating that the n-3 LCFA levels in blood and tissues could be increased without eating marine foods, and therefore without promoting unsustainable overfishing, and without damaging marine ecology.
Published: 2017

341. Molecular Classification of Hepatocellular Adenoma Associates With Risk Factors, Bleeding, and Malignant Transformation

Author: Viviane Gnemmi, Gabrielle Couchy, Jean-Frédéric Blanc, Eric Savier, Jean Saric, Georges-Philippe Pageaux, Christophe Letoublon, Jean-Charles Nault, Guillaume Morcrette, Valérie Vilgrain, Brigitte Le Bail, Denis Castaing, Christophe Laurent, Anne de Muret, Vincenzo Mazzaferro, Yannick Bacq, Alain Luciani, Julien Calderaro, Valérie Paradis, Laurence Chiche, Nora Frulio, Luigi Terraciano, Emmanuel Jacquemin, Emmanuel Boleslawski, Jeanne Ramos, Sandrine Imbeaud, Benoit Terris, Marie Christine Saint Paul, Brigitte Bancel, Jean-Christophe Vaillant, François Paye, Catherine Guettier, Jacques Belghiti, Janick Selves, Daniel Azoulay, Camilla Pilati, Eric Letouzé, Dominique Wendum, Stefano Caruso, Charles Balabaud, Pascal Bourlier, Claire Castain, Jean-Michel Fabre, Jessica Zucman-Rossi, Alexis Laurent, Sophie Prevot, Zin Benchellal, Fanny Dujardin, Monique Fabre, Sandra Rebouissou, Paulette Bioulac-Sage, Nathalie Sturm, Philippe Labrune, Jean-Marie Péron, Alberto Quaglia, Jean-Yves Scoazec, Université Paris 13 (UP13), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Service d'Anatomo-Pathologie, 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Gustave Roussy (IGR), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Département d'anatomie et cythologie pathologique, CHU Grenoble-Hôpital Michallon, Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], 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, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anatomie Pathologique [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Service d'Anatomopathologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service d'oncologie médicale [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), 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 d'Anatomie et cytologie pathologiques [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Paul Brousse-Université Paris-Sud - Paris 11 (UP11), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), CHU Necker - Enfants Malades [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), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Malignant transformation, 0302 clinical medicine, Risk Factors, Cytokine Receptor gp130, GTP-Binding Protein alpha Subunits, Gs, Hepatocyte Nuclear Factor 1-alpha, Child, Telomerase, beta Catenin, Inhibin-beta Subunits, Aged, 80 and over, biology, Liver Neoplasms, Gastroenterology, hepatocellular carcinoma, Middle Aged, Protein-Tyrosine Kinases, Neoplasm Proteins, 3. Good health, HNF1A, Cell Transformation, Neoplastic, 030220 oncology & carcinogenesis, Fyn-related kinase, Female, 030211 gastroenterology & hepatology, Gene Fusion, Signal Transduction, Adenoma, Adult, STAT3 Transcription Factor, Carcinoma, Hepatocellular, Adolescent, hepatocellular adenoma, Hemorrhage, Zinc Finger Protein GLI1, Young Adult, 03 medical and health sciences, sonic hedgehog, Chromogranins, GNAS complex locus, medicine, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Hedgehog Proteins, benign liver tumor, Unclassified Hepatocellular Adenoma, Aged, Hepatology, Sequence Analysis, RNA, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Janus Kinase 2, Hepatocellular adenoma, medicine.disease, Mutation, biology.protein, Cancer research, Inflammatory Hepatocellular Adenoma, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Transcriptome
Abstract: International audience; BACKGROUND & AIMS: Hepatocellular adenomas (HCAs) are benign liver tumors that can be assigned to molecular subtypes based on inactivating mutations in hepatocyte nuclear factor 1A, activating mutations in β-catenin, or activation of inflammatory signaling pathways. We aimed to update the classification system for HCA and associate the subtypes with disease risk factors and complications.METHODS: We analyzed expression levels of 20 genes and sequenced exon regions of 8 genes (HNF1A, IL6ST, CTNNB1, FRK, STAT3, GNAS, JAK1, and TERT) in 607 samples of 533 HCAs from 411 patients, collected from 28 centers mainly in France from 2000 and 2014. We performed gene expression profile, RNA sequence, whole-exome and genome sequence, and immunohistochemical analyses of select samples. Molecular data were associated with risk factors, histopathology, bleeding, and malignant transformation.RESULTS: Symptomatic bleeding occurred in 14% of the patients (85% of cases were female, median age, 38 years); 7% of the nodules were borderline between HCA and hepatocellular carcinoma, and 3% of patients developed hepatocellular carcinoma from HCA. Based on molecular features, we classified HCA into 8 subgroups. One new subgroup, composed of previously unclassified HCA, represented 4% of HCAs overall and was associated with obesity and bleeding. These tumors were characterized by activation of sonic hedgehog signaling, due to focal deletions that fuse the promoter of INHBE with GLI1. Analysis of genetic heterogeneity among multiple HCAs, from different patients, revealed a molecular subtype field effect; multiple tumors had different mutations that deregulated similar pathways. Specific molecular subtypes of HCA associated with various HCA risk factors, including imbalances in estrogen or androgen hormones. Specific molecular subgroup of HCA with β-catenin and sonic hedgehog activation associated with malignant transformation and bleeding, respectively.CONCLUSIONS: Using sequencing and gene expression analyses, we identified a subgroup of HCA characterized by fusion of the INHBE and GLI1 genes and activation of sonic hedgehog pathway. Molecular subtypes of HCAs associated with different patients' risk factors for HCA, disease progression, and pathology features of tumors. This classification system might be used to select treatment strategies for patients with HCA.
Published: 2017

342. Socioeconomic position and outdoor nitrogen dioxide (NO2) exposure in Western Europe: A multi-city analysis

Author: Mark J. Nieuwenhuijsen, Ming-Yi Tsai, Nicole Probst-Hensch, Emilie Burte, Nino Künzli, Anne-Elie Carsin, Xavier Basagaña, Bert Brunekreef, Jean Bousquet, Alessandro Marcon, Margaux Sanchez, Kees de Hoogh, Lars Modig, Valérie Siroux, Bénédicte Jacquemin, Rachel Nadif, Isabelle Pin, Josep M. Antó, Jordi Sunyer, Morgane Stempfelet, Sofia Temam, Roberto Bono, Bruna Galobardes, Deborah Jarvis, Martin Adam, Dirk Keidel, Nicole Le Moual, Joachim Heinrich, Medical Research Council (MRC), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Département de pédiatrie, CHU Grenoble-Hôpital Michallon, Institut de Veille Sanitaire (INVS), dIRAS RA-2, and LS IRAS EEPI ME (Milieu epidemiologie)
Subjects: Socioeconomic position, Air pollution, 010501 environmental sciences, medicine.disease_cause, 01 natural sciences, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Environmental protection, Environmental health, 11. Sustainability, MD Multidisciplinary, medicine, Nitrogen dioxide, 030212 general & internal medicine, lcsh:Environmental sciences, 0105 earth and related environmental sciences, General Environmental Science, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, lcsh:GE1-350, Environmental inequality, Europe, social sciences, Geography, chemistry, 13. Climate action, Western europe, 8. Economic growth, population characteristics, Environmental Sciences
Abstract: Background: Inconsistent associations between socioeconomic position (SEP) and outdoor air pollution have been reported in Europe, but methodological differences prevent any direct between-study comparison. Objectives: Assess and compare the association between SEP and outdoor nitrogen dioxide (NO2) exposure as a marker of traffic exhaust, in 16 cities from eight Western European countries. Methods: Three SEP indicators, two defined at individual-level (education and occupation) and one at neighborhood-level (unemployment rate) were assessed in three European multicenter cohorts. NO2 annual concentration exposure was estimated at participants' addresses with land use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE; http://www.escapeproject.eu/). Pooled and city-specific linear regressions were used to analyze associations between each SEP indicator and NO2. Heterogeneity across cities was assessed using the Higgins' I-squared test (I2). Results: The study population included 5692 participants. Pooled analysis showed that participants with lower individual-SEP were less exposed to NO2. Conversely, participants living in neighborhoods with higher unemployment rate were more exposed. City-specific results exhibited strong heterogeneity (I2 > 76% for the three SEP indicators) resulting in variation of the individual- and neighborhood-SEP patterns of NO2 exposure across cities. The coefficients from a model that included both individual- and neighborhood-SEP indicators were similar to the unadjusted coefficients, suggesting independent associations. Conclusions: Our study showed for the first time using homogenized measures of outcome and exposure across 16 cities the important heterogeneity regarding the association between SEP and NO2 in Western Europe. Importantly, our results showed that individual- and neighborhood-SEP indicators capture different aspects of the association between SEP and exposure to air pollution, stressing the importance of considering both in air pollution health effects studies. The ESCAPE study, funded by the European Community's Seventh Framework Program (FP7/2007-2011) under grant agreement no. 211250 (http://www.escapeproject.eu/).
Published: 2017

343. Harnessing Si CMOS technology for quantum information

Author: S. Barraud, Xavier Jehl, Benoit Bertrand, L. Bourdet, T. Meunier, Baptiste Jadot, Louis Hutin, Romain Maurand, Yann-Michel Niquet, M. Vinet, S. De Franceschi, Matias Urdampilleta, M. Sanquer, Christopher Bäuerle, H. Bohuslavskyi, Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Clinique Cardiologie et Hypertension Artérielle, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Laboratoire de Transport Electronique Quantique et Supraconductivité (LaTEQS), PHotonique, ELectronique et Ingénierie QuantiqueS (PHELIQS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Circuits électroniques quantiques Alpes (NEEL - QuantECA), Institut Néel (NEEL), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratory of Atomistic Simulation (LSIM ), Modélisation et Exploration des Matériaux (MEM), European Project: 688539,MOSQUITO, Circuits électroniques quantiques Alpes (QuantECA ), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: Coupling, Computer science, 02 engineering and technology, 021001 nanoscience & nanotechnology, 01 natural sciences, Computer Science::Emerging Technologies, CMOS, [PHYS.QPHY]Physics [physics]/Quantum Physics [quant-ph], Logic gate, Qubit, 0103 physical sciences, Scalability, Electronic engineering, Hardware_ARITHMETICANDLOGICSTRUCTURES, Quantum information, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, 010306 general physics, 0210 nano-technology, Quantum tunnelling, ComputingMilieux_MISCELLANEOUS, Spin-½
Abstract: We present some recent progress towards the implementation of the basic building blocks of quantum information processing derived from a Si CMOS technology platform. In our approach, characterized by an emphasis on foundry compatibility in terms of processes and materials, the so-called qubits are encoded in the spin degree of freedom of gate-confined elementary charges. After introducing various qubit manipulation, coupling and readout schemes, we discuss some prospects for scalability, and in particular some potential advantages of the FDSOI technology.
Published: 2017
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344. DNA Methylation Is an Independent Prognostic Marker of Survival in Adrenocortical Cancer

Author: Anne, Jouinot, Guillaume, Assie, Rossella, Libe, Martin, Fassnacht, Thomas, Papathomas, Olivia, Barreau, Bruno, de la Villeon, Simon, Faillot, Nadim, Hamzaoui, Mario, Neou, Karine, Perlemoine, Fernande, Rene-Corail, Stéphanie, Rodriguez, Mathilde, Sibony, Frédérique, Tissier, Bertrand, Dousset, Silviu, Sbiera, Cristina, Ronchi, Matthias, Kroiss, Esther, Korpershoek, Ronald, de Krijger, Jens, Waldmann, Detlef, K, Bartsch, Marcus, Quinkler, Magalie, Haissaguerre, Antoine, Tabarin, Olivier, Chabre, Nathalie, Sturm, Michaela, Luconi, Franco, Mantero, Massimo, Mannelli, Regis, Cohen, Véronique, Kerlan, Philippe, Touraine, Gaelle, Barrande, Lionel, Groussin, Xavier, Bertagna, Eric, Baudin, Laurence, Amar, Felix, Beuschlein, Eric, Clauser, Joel, Coste, Jérôme, Bertherat, Pathology, Institut Cochin (IC UM3 (UMR 8104 / U1016)), 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), CHU Cochin [AP-HP], Department of Psychiatry, Chirurgie digestive, hépato-biliaire et endocrinienne [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München (LMU), Comprehensive Cancer Center Mainfranken, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Department of Pathology, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Clinical Genetics, Département d'endocrinologie - Bordeaux 2, Université Bordeaux Segalen - Bordeaux 2, Groupement Hospitalier Lyon-Est (GHE), Hospices Civils de Lyon (HCL), Laboratoire de Cytologie, Département d'Anatomie et de Cytologie Pathologiques, CHU Grenoble-Hôpital Michallon, Department of Endocrinology and Diabetes Mellitus, Hôpital Delafontaine, Service d'Endocrinologie (CHRU - Endocrino), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Département d'endocrinologie et Médecine Reproductive [AP-HP Hôpital Pitié-Salpétrière], AP-HP Hôpital Universitaire Pitié Salpêtrière - GHU Pitié Salpêtrière, Centre Hospitalier Régional d'Orléans (CHR), Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Université de Brest (UBO)-Université de Brest (UBO), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional d'Orléans (CHRO), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
Subjects: 0301 basic medicine, Male, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, medical, Biochemistry, 0302 clinical medicine, Endocrinology, Adrenocortical Carcinoma, Methylation, DNA, Neoplasm, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Middle Aged, Prognosis, 3. Good health, Tumor Burden, Diabetes and Metabolism, Survival Rate, CpG site, 030220 oncology & carcinogenesis, Cohort, DNA methylation, Female, Adult, medicine.medical_specialty, Context (language use), Biology, Disease-Free Survival, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Journal Article, Humans, Survival rate, Aged, Neoplasm Staging, Proportional Hazards Models, Retrospective Studies, Biochemistry, medical, Proportional hazards model, Biochemistry (medical), Retrospective cohort study, DNA Methylation, Adrenal Cortex Neoplasms, 030104 developmental biology, Ki-67 Antigen, Multivariate Analysis, CpG Islands, Multiplex Polymerase Chain Reaction, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Context:Adrenocortical cancer (ACC) is an aggressive tumor with a heterogeneous outcome. Prognostic stratification is difficult even based on tumor stage and Ki67. Recently integrated genomics studies have demonstrated that CpG islands hypermethylation is correlated with poor survival.Objective:The goal of this study was to confirm the prognostic value of CpG islands methylation on an independent cohort.Design:Methylation was measured by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA).Setting:MS-MLPA was performed in a training cohort of 50 patients with ACC to identify the best set of probes correlating with disease-free survival (DFS) and overall survival (OS). These outcomes were validated in an independent cohort from 21 ENSAT centers.Patients:The validation cohort included 203 patients (64% women, median age 50 years, 80% localized tumors).Main Outcome Measures:DFS and OS.Results:In the training cohort, mean methylation of 4 genes (PAX5, GSTP1, PYCARD, PAX6) was the strongest methylation marker. In the validation cohort, methylation was a significant prognostic factor of DFS (P < 0.0001) and OS (P < 0.0001). Methylation, Ki67, and ENSAT stage were combined in multivariate models. For DFS, methylation (P = 0.0005) and stage (P < 0.0001) but not Ki67 (P = 0.19) remained highly significant. For OS, methylation (P = 0.0006), stage (P < 0.0001), and Ki67 (P = 0.024) were independent prognostic factors.Conclusions:Tumor DNA methylation emerges as an independent prognostic factor in ACC. MS-MLPA is readily compatible with clinical routine and should enhance our ability for prognostication and precision medicine.
Published: 2017

345. Sex Differences in Spontaneous Degranulation Activity of Intrahepatic Natural Killer Cells during Chronic Hepatitis B: Association with Estradiol Levels

Author: Macek Jilkova, Zuzana, Decaens, Thomas, Marlu, Alice, Marche, Hélène, Jouvin-Marche, Evelyne, Marche, Patrice N., Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Département de Gastroentérologie et hépatologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and MARCHE, Patrice
Subjects: Male, [SDV.IMM] Life Sciences [q-bio]/Immunology, Article Subject, Estradiol, virus diseases, Flow Cytometry, digestive system diseases, Cell Line, Killer Cells, Natural, Hepatitis B, Chronic, Sex Factors, Liver, lcsh:Pathology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Humans, Female, Research Article, lcsh:RB1-214
Abstract: International audience; Major sex differences are observed in the prevalence, intensity, and severity of hepatitis B virus (HBV) infection. Here, we investigated degranulation activity of circulating and intrahepatic natural killer (NK) cells from HBV and HCV chronically infected patients before any treatment (n = 125). The frequency of CD107 + NK cells in the female liver was significantly higher compared to that in males during chronic HBV infection (p = 0 002) and correlated with the plasma levels of estradiol (correlation coefficient r = 0 634; p < 0 0001). Our results clearly show sex differences in degranulation activity of intrahepatic NK cells of HBV-infected patients. This probably contributes to the ability of females to better deal with HBV disease.
Published: 2017

346. Consolidation anti-CD22 fractionated radioimmunotherapy with 90Y-epratuzumab tetraxetan following R-CHOP in elderly patients with diffuse large B-cell lymphoma: a prospective, single group, phase 2 trial

Author: Isabelle Soubeyran, Anne Moreau, David M. Goldenberg, Amandine Pallardy, Jean-Philippe Vuillez, Jacques Barbet, Loïc Campion, Olivier Tournilhac, Nadine Morineau, Caroline Bodet-Milin, Krimo Bouabdallah, Thierry Lamy, Etienne Garin, Philippe Moreau, Steven Le Gouill, Pierre Soubeyran, Pierre-Yves Salaun, Hervé Maisonneuve, Anne-Laure Cazeau, Bénédicte Deau, Sophie Sadot, Valérie Gouilleux-Gruart, Françoise Kraeber-Bodéré, Henry Jardel, Remy Gressin, Emmanuel Gyan, Christian Berthou, Etienne Daguindau, William A. Wegener, Marie-Pierre Moles, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hématologie, Centre hospitalier La Roche-Sur-Yon, Centre René Gauducheau, CRLCC René Gauducheau, Plateforme de génétique moléculaire des cancers d'Aquitaine, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Service d'hématologie clinique, Hôpital Hôtel-Dieu [Paris], Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias - Clermont Auvergne (CHELTER), Université Clermont Auvergne (UCA), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Service de Médecine Interne, CH Bretagne Atlantique, Centre Catherine-de-Sienne [Nantes] (CCS), Université Mohamed Boudiaf de M'sila, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Grenoble-Hôpital Michallon, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Institut de Recherche sur la Fusion par confinement Magnétique (IRFM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Microenvironnement et remodelage, Service de médecine nucléaire, Centre régional de lutte contre le cancer-Centre régional de lutte contre le cancer, Radiopharmaceutiques biocliniques, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Développement normal et pathologique des lymphocytes et signalisation, Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Accélérateur pour la Recherche en Radiochimie et Oncologie [Nantes Atlantique] (GIP ARRONAX), Université de Nantes (UN)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Garden State Cancer Center (GSCC), Garden State Cancer Center, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Service de Médecine Nucléaire [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Médecine Onco-hématologie [La Roche sur Yon], Centre Hospitalier Universitaire de Nantes, Génétique tumorale - Pathologie, UNICANCER-UNICANCER-CHU Bordeaux [Bordeaux], CIC Plurithématique de Nantes, Institut National de la Santé et de la Recherche Médicale (INSERM)-Ministère des Affaires sociales et de la Santé-Direction générale de l'offre de soins (DGOS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Médecine interne - Maladies hématologiques - Maladies infectieuses [Vannes], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), PRES Université Nantes Angers Le Mans (UNAM), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de cancérologie et d'hématologie, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Département de Médecine Nucléaire (NANTES - Médecine Nucléaire), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Médecine Nucléaire [Bordeaux], Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-CRLCC Eugène Marquis (CRLCC), CHRU Brest - Service de médecine nucléaire (CHU - BREST - Med Nucléaire), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Recherches en cancérologie, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunomedics, Inc., Université de Rennes (UR)-Hôpital Pontchaillou, CHU Bordeaux [Bordeaux]-Institut Bergonié [Bordeaux], 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)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-CRLCC Eugène Marquis (CRLCC), Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux]-Centre Régional de Lutte Contre le Cancer Institut Bergonié (Bordeaux), Centre Hospitalier Bretagne Atlantique [Vannes], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital Morvan [Brest], CHU Cochin [AP-HP], and Institut Bergonié - CRLCC Bordeaux
Subjects: 0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Chemoimmunotherapy, immune system diseases, Internal medicine, hemic and lymphatic diseases, medicine, education, ComputingMilieux_MISCELLANEOUS, education.field_of_study, business.industry, Induction chemotherapy, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, 3. Good health, Surgery, Transplantation, 030104 developmental biology, 030220 oncology & carcinogenesis, Radioimmunotherapy, Rituximab, business, Epratuzumab, Diffuse large B-cell lymphoma, medicine.drug
Abstract: BACKGROUND: Radioimmunotherapy represents a potential option as consolidation after chemoimmunotherapy in patients with diffuse large B-cell lymphoma who are not candidates for transplantation. We aimed to assess activity and toxicity of fractionated radioimmunotherapy using anti-CD22 (90)Y-epratuzumab tetraxetan as consolidation after front-line induction chemoimmunotherapy in untreated elderly patients with diffuse large B-cell lymphoma. METHODS: We did a prospective, single-group, phase 2 trial at 28 hospitals in France, with patients recruited from 17 hospitals. Eligible patients were aged 60-80 years with bulky stage 2-3 or stage 3-4 CD20-positive diffuse large B-cell lymphoma, previously untreated, and not eligible for transplantation. Patients received six cycles of R-CHOP (rituximab [375 mg/m(2)], cyclophosphamide [750 mg/m(2)], doxorubicin [50 mg/m(2)], and vincristine [1·4 mg/m(2), up to 2 mg] all on day 1, and prednisone [40 mg/m(2)] daily for 5 days), administered every 14 days. 6-8 weeks after R-CHOP, responders received two doses of 15 mCi/m(2) (555 MBq/m(2)) (90)Y-epratuzumab tetraxetan administered 1 week apart. The primary endpoint was 2 year event-free survival in all registered eligible patients who received at least 1 day of study treatment; the safety analysis was done in the same population. This trial is registered with ClinicalTrials.gov, number NCT00906841. FINDINGS: Between Oct 22, 2008, and Dec 16, 2010, we recruited 75 patients, of whom four (5%) were excluded after central pathology review; hence, 71 (95%) patients were included in the analysis. All patients started induction treatment; 57 (80%) received radioimmunotherapy. With a median follow-up of 37 months (IQR 30-44), the estimated 2 year event-free survival was 75% (95% CI 63-84). Radioimmunotherapy toxicity consisted of grade 3-4 thrombocytopenia in 48 (84%) of 57 patients and neutropenia in 45 (79%) of 57 patients. One patient developed myelodysplastic syndrome 28 months after receiving radioimmunotherapy and one patient developed acute myeloid leukaemia 5 months after receiving radioimmunotherapy. INTERPRETATION: Fractionated radioimmunotherapy with (90)Y-epratuzumab tetraxetan might be appropriate for response consolidation after induction chemotherapy in older patients with advanced diffuse large B-cell lymphoma, but further comparative studies are needed. FUNDING: Immunomedics, Amgen, Canceropole Grand Ouest, the GOELAMS/LYSA group and the French National Agency for Research (Investissements d'Avenir).
Published: 2017

347. A Single Test Combining Blood Markers and Elastography is More Accurate Than Other Fibrosis Tests in the Main Causes of Chronic Liver Diseases

Author: Dominique Salmon, Paul Calès, Victor de Ledinghen, Brigitte Le Bail, Alexandra Ducancelle, Julien Vergniol, Jean-Pierre Zarski, Vincent Leroy, Eric Nguyen Khac, Nathalie Sturm, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépato-gastroentérologie [CHU Grenoble Alpes], Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Département d'anatomie et cythologie pathologique, CHU Grenoble-Hôpital Michallon, Laboratoire d'anatomie pathologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Département d'hépato-gastroentérologie, CHU Grenoble-Université Grenoble Alpes (UGA), Service d'Hépato-gastroentérologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Service Maladies infectieuses et tropicales [AP-HP Hôpital Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Centre d'investigation de la fibrose hépatique [CHU de Bordeaux] (Hôpital Haut-Lévêque ), Hôpital Haut-Lévêque [CHU de Bordeaux], Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), and Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble
Subjects: Adult, Liver Cirrhosis, Male, Pathology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Disease, Severity of Illness Index, End Stage Liver Disease, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, Severity of illness, Medicine, Blood test, Humans, Aspartate Aminotransferases, Prospective Studies, Stage (cooking), Prospective cohort study, Retrospective Studies, medicine.diagnostic_test, business.industry, Platelet Count, Liver Diseases, Fatty liver, Gastroenterology, Middle Aged, medicine.disease, 3. Good health, Liver, ROC Curve, 030220 oncology & carcinogenesis, Elasticity Imaging Techniques, 030211 gastroenterology & hepatology, Female, Elastography, business, Biomarkers
Abstract: International audience; BACKGROUND AND GOAL: International guidelines suggest combining a blood test and liver stiffness measurement (LSM) to stage liver fibrosis in chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD). Therefore, we compared the accuracies of these tests between the main etiologies of chronic liver diseases.STUDY: Overall, 1968 patients were included in 5 etiologies: CHC: 698, chronic hepatitis B: 152, human immunodeficiency virus/CHC: 628, NAFLD: 225, and alcoholic liver disease (ALD): 265. Sixteen tests [13 blood tests, LSM (Fibroscan), 2 combined: FibroMeters] were evaluated. References were Metavir staging and CHC etiology. Accuracy was evaluated mainly with the Obuchowski index (OI) and accessorily with area under the receiver operating characteristics (F≥2, F≥3, cirrhosis).RESULTS: OIs in CHC were: FibroMeters: 0.812, FibroMeters: 0.785 to 0.797, Fibrotest: 0.762, CirrhoMeters: 0.756 to 0.771, LSM: 0.754, Hepascore: 0.752, FibroMeter: 0.750, aspartate aminotransferase platelet ratio index: 0.742, Fib-4: 0.741. In other etiologies, most tests had nonsignificant changes in OIs. In NAFLD, CHC-specific tests were more accurate than NAFLD-specific tests. The combined FibroMeters had significantly higher accuracy than their 2 constitutive tests (FibroMeters and LSM) in at least 1 diagnostic target in all etiologies, except in ALD where LSM had the highest OI, and in 3 diagnostic targets (OIs and 2 area under the receiver operating characteristics) in CHC and NAFLD.CONCLUSIONS: Some tests developed in CHC outperformed other tests in their specific etiologies. Tests combining blood markers and LSM outperformed single tests, validating recent guidelines and extending them to main etiologies. Noninvasive fibrosis evaluation can thus be simplified in the main etiologies by using a unique test: either LSM alone, especially in ALD, or preferably combined to blood markers.
Published: 2017

348. Identification of pyrrolopyrimidine derivative PP-13 as a novel microtubule-destabilizing agent with promising anticancer properties

Author: Pauline Gilson, Fernando Josa-Prado, Claire Beauvineau, Delphine Naud-Martin, Laetitia Vanwonterghem, Florence Mahuteau-Betzer, Alexis Moreno, Pierre Falson, Laurence Lafanechère, Véronique Frachet, Jean-Luc Coll, Jose Fernando Díaz, Amandine Hurbin, Benoit Busser, Hurbin, Amandine, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Dpt biochimie, toxicologie, pharmacologie [CHU Grenoble], CHU Grenoble, Centro de Investigaciones Biológicas (CSIC), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Chimie, Modélisation et Imagerie pour la Biologie [Orsay], Université Paris-Sud - Paris 11 (UP11)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Microbiologie moléculaire et biochimie structurale / Molecular Microbiology and Structural Biochemistry (MMSB), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Institut Curie, the CNRS, the INSERM, and by grants from La Fondation de France, La Ligue contre le Cancer (comité de l’Isère), Cancéropôle CLARA (Lyon Auvergne Rhône-Alpes), and BFU2016–75319-R (AEI/FEDER, UE) from Ministerio de Economia y Competitividad (JFD)., Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Biochemistry Pharmacology and Toxicology Department, Centre Hospitalo-Universitaire de Grenoble, Institut de biologie et chimie des protéines [Lyon] (IBCP), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL), Université Grenoble Alpes - UFR Pharmacie ( UGA UFRP ), Université Grenoble Alpes ( UGA ), Unité de pharmacologie chimique et génétique et d'imagerie ( UPCGI - UMR 8151 / UMR_S 1022 ), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Conception, synthèse et vectorisation de biomolécules. ( CSVB ), INSTITUT CURIE-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ), Laboratoire d'Etudes et de Recherches Appliquées en Sciences Sociales ( LERASS ), Université Paul-Valéry - Montpellier 3 ( UM3 ) -Université Toulouse - Jean Jaurès ( UT2J ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Groupe Plateforme et Moyens Scientifiques et techniques communs / Centre de Criblage pour Molécules Bio-Actives ( GPMS / CMBA ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), INSERM U823, équipe 5 (cibles diagnostiques ou thérapeutiques et vectorisation de drogues dans le cancer du poumon), Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Biochimie des Cancers et Biothérapies, CHU Grenoble-Hôpital Michallon-Hôpital Michallon, and Falson, pierre
Subjects: Cell Survival, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, lcsh:Medicine, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Chick Embryo, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Article, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Tubulin, Cell Line, Tumor, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Animals, Humans, Pyrroles, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], lcsh:Science, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], ComputingMilieux_MISCELLANEOUS, Cell Proliferation, lcsh:R, Neoplasms, Experimental, Xenograft Model Antitumor Assays, Tubulin Modulators, Pyrimidines, Drug Resistance, Neoplasm, lcsh:Q, Drug Screening Assays, Antitumor, Colchicine
Abstract: International audience; Despite the emergence of targeted therapies and immunotherapy, chemotherapy remains the gold-standard for the treatment of most patients with solid malignancies. Spindle poisons that interfere with microtubule dynamics are commonly used in chemotherapy drug combinations. However, their troublesome side effects and the emergence of chemoresistance highlight the need for identifying alternative agents. We performed a high throughput cell-based screening and selected a pyrrolopyrimidine molecule (named PP-13). In the present study, we evaluated its anticancer properties in vitro and in vivo. We showed that PP-13 exerted cytotoxic effects on various cancer cells, including those resistant to current targeted therapies and chemotherapies. PP-13 induced a transient mitotic blockade by interfering with both mitotic spindle organization and microtubule dynamics and finally led to mitotic slippage, aneuploidy and direct apoptotic death. PP-13 was identified as a microtubule-targeting agent that binds directly to the colchicine site in β-tubulin. Interestingly, PP-13 overcame the multidrug-resistant cancer cell phenotype and significantly reduced tumour growth and metastatic invasiveness without any noticeable toxicity for the chicken embryo in vivo. Overall, PP-13 appears to be a novel synthetic microtubule inhibitor with interesting anticancer properties and could be further investigated as a potent alternative for the management of malignancies including chemoresistant ones. In the last two decades, advances in the understanding of carcinogenesis have revolutionized the management of cancer patients with the development of targeted therapies and immunotherapy. Identification of genetic alterations in subsets of cancers leading to different subcellular signals of tumour growth and progression elicited the clinical use of oncogene-targeted therapies for patients harbouring such anomalies 1-4. In lung cancers with EGFR-activating mutations, anti-EGFR therapies, including gefitinib, erlotinib, and afatinib, have been shown to improve progression-free survival and were approved as first-line options 5. However, despite the initial response, resistance mechanisms almost inevitably ensue and limit the long-term potency of targeted therapies 6, 7. Moreover, efforts are still needed for the management of patients without targetable oncogenic driver
Published: 2017

349. Usefulness of 18F-FDG PET Associated With a High-Fat, Low-Carbohydrate Preparation for the Detection of a Myocardial-Embedded Metastasis

Author: Pierre-Yves Marie, Laurent Riou, Damien Mandry, Loïc Djaileb, Antoine Verger, Service de médecine nucléaire et biophysique, CHU Grenoble-Hôpital Michallon, Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Radiopharmaceutiques biocliniques (LRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Nancyclotep- Experimental Imaging Platform = Plate-forme d'imagerie moléculaire, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Lorraine (UL), Service de Médecine Nucléaire [Nancy], and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Subjects: Male, medicine.medical_specialty, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 030204 cardiovascular system & hematology, Ventricular tachycardia, 030218 nuclear medicine & medical imaging, Metastasis, Heart Neoplasms, 03 medical and health sciences, 0302 clinical medicine, Text mining, Fluorodeoxyglucose F18, Renal cell carcinoma, medicine, Carcinoma, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Ingestion, Radiology, Nuclear Medicine and imaging, cardiovascular diseases, Carcinoma, Renal Cell, ComputingMilieux_MISCELLANEOUS, Aged, medicine.diagnostic_test, business.industry, General Medicine, medicine.disease, Kidney Neoplasms, 3. Good health, medicine.anatomical_structure, Ventricle, Positron emission tomography, Positron-Emission Tomography, cardiovascular system, Radiology, Radiopharmaceuticals, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: The detection of left ventricle metastases is highly relevant because of the risk of severe adverse outcomes such as ventricular arrhythmia. We report herein the case of a 68-year-old man who presented with a ventricular tachycardia due to a myocardial metastasis from a renal cell carcinoma. The metastasis was embedded within the left ventricular lateral wall. It was identified on the basis of persistent F-FDG focal uptake following the ingestion of a high-fat, low-carbohydrate preparation.
Published: 2017

350. New advances in DPYD genotype and risk of severe toxicity under capecitabine

Author: Jean-Louis Merlin, Frédéric Pinguet, Fabienne Thomas, N. Dohollou, Alexandre Evrard, Philippe Follana, Mireille Mousseau, Emmanuel Chamorey, Christophe Ferrand, Gérard Milano, Marie-Christine Etienne-Grimaldi, Gilles Romieu, André B.P. van Kuilenburg, Laurence Llorca, Rémy Largillier, V. Servent, Thomas Bachelot, Judith L Meijer, Litaty Mbatchi, David Salgado, Jean-Christophe Boyer, Jean-Pierre Desvignes, Véronique Diéras, Jacques Bonneterre, Yann Château, Christine Bobin-Dubigeon, Christophe Béroud, Etienne Chatelut, Henri Roché, Anthony Gonçalves, Loic Chaigneau, Jean-Marc Ferrero, Xavier Pivot, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Génétique Médicale et Génomique Fonctionnelle (GMGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Institut Claudius Regaud, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), CRLCC Val d'Aurelle - Paul Lamarque, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Oncogénèse et progression tumorale, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut Curie [Paris], Centre Azureen de cancérologie, Service d'oncologie médicale, CHU Grenoble-Hôpital Michallon, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Département d'oncologie médicale, Département de Sénologie, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, Université Lille Nord de France (COMUE)-UNICANCER, Polyclinique Bordeaux Nord Aquitaine, CRLCC Antoine Lacassagne, Centre Hospitalier Régional Universitaire de Nîmes ( CHRU Nîmes ), Institut de génétique humaine ( IGH ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche en Cancérologie de Montpellier ( IRCM - U1194 Inserm - UM ), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] ( AMC ), University of Amsterdam [Amsterdam] ( UvA ), Institut de cancérologie de l'Ouest - Nantes ( ICO Nantes ), CRLCC Paul Papin-CRLCC René Gauducheau, CRLCC Institut Claudius Regaud, Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), Centre de Recherche en Automatique de Nancy ( CRAN ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Val d'Aurelle-Paul Lamarque, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Centre Léon Bérard [Lyon], Service d'oncologie Médicale, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Institut Curie, Centre de Recherche en Cancérologie de Marseille ( CRCM ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université ( AMU ), CRLCC Oscar Lambret, Center Oscar Lambret, Génétique Médicale et Génomique Fonctionnelle ( GMGF ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Université de Lille-UNICANCER-Université de Lille-UNICANCER, Université de Lille-UNICANCER, Polyclinique Bordeaux Nord Aquitaine (PBNA), AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, CCA - Cancer biology and immunology, Laboratory Genetic Metabolic Diseases, CCA -Cancer Center Amsterdam, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), and Salgado, David
Subjects: Oncology, lcsh:Medicine, Toxicology, Pathology and Laboratory Medicine, 030226 pharmacology & pharmacy, Biochemistry, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Predictive toxicology, Genotype, Medicine and Health Sciences, Prospective Studies, Prospective cohort study, lcsh:Science, Exome, Multidisciplinary, Nucleotides, Genomics, Middle Aged, 3. Good health, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], 030220 oncology & carcinogenesis, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Cancer treatment, Female, medicine.drug, Research Article, Adult, medicine.medical_specialty, Antimetabolites, Antineoplastic, Genotyping, Single-nucleotide polymorphism, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Genome Complexity, Research and Analysis Methods, Polymorphism, Single Nucleotide, Capecitabine, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Dihydropyrimidine dehydrogenase, Genetics, Humans, Uracils, Molecular Biology Techniques, Molecular Biology, Dihydrouracil Dehydrogenase (NADP), Alleles, Aged, Nucleobases, Toxicity, business.industry, lcsh:R, [ SDV.SP.PHARMA ] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Biology and Life Sciences, Computational Biology, Introns, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Genetic Loci, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, DPYD, lcsh:Q, business, Biomarkers
Abstract: International audience; Background: Deficiency in dihydropyrimidine dehydrogenase (DPD) enzyme is the main cause of severe and lethal fluoropyrimidine-related toxicity. Various approaches have been developed for DPD-deficiency screening, including DPYD genotyping and phenotyping. The goal of this prospective observational study was to perform exhaustive exome DPYD sequencing and to examine relationships between DPYD variants and toxicity in advanced breast cancer patients receiving capecitabine.Methods: Two-hundred forty-three patients were analysed (88.5% capecitabine monotherapy). Grade 3 and grade 4 capecitabine-related digestive and/or neurologic and/or hemato-toxicities were observed in 10.3% and 2.1% of patients, respectively. DPYD exome, along with flanking intronic regions 3’UTR and 5’UTR, were sequenced on MiSeq Illumina. DPD phenotype was assessed by pre-treatment plasma uracil (U) and dihydrouracil (UH2) measurement.Results: Among the 48 SNPs identified, 19 were located in coding regions, including 3 novel variations, each observed in a single patient (among which, F100L and A26T, both pathogenic in silico). Combined analysis of deleterious variants *2A, I560S (*13) and D949V showed significant association with grade 3–4 toxicity (sensitivity 16.7%, positive predictive value (PPV) 71.4%, relative risk (RR) 6.7, p16 ng/ml) did not substantially increase the sensitivity, while impairing PPV and RR.Conclusions: Exploring an extended set of deleterious DPYD variants improves the performance of DPYD genotyping for predicting both grade 3–4 and grade 4 toxicities (digestive and/or neurologic and/or hematotoxicities) related to capecitabine, as compared to conventional genotyping restricted to consensual variants *2A, *13 and D949V.
Published: 2017

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