Author: "CIC - CHU Henri Mondor" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"CIC - CHU Henri Mondor"' showing total 39 results

Start Over Author "CIC - CHU Henri Mondor"

39 results on '"CIC - CHU Henri Mondor"'

1. Clinical features, therapeutic choice and response by phototype in psoriasis: analysis of the French PsoBioTeq cohort

Author: Salle-Siri, Romain, Tubach, Florence, Arlegui, Hugo, Curmin, Raphaëlle, Viguier, Manuelle, Beylot-Barry, Marie, Dupuy, Alain, Bénéton, Nathalie, Joly, Pascal, de Rycke, Yann, Jullien, Denis, Mahé, Emmanuel, Paul, Carle, Richard, Marie‐aleth, Bachelez, Hervé, Zago, Marilyn, Chosidow, Olivier, Sbidian, Emilie, Hôpital Henri Mondor, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Robert Debré, BoRdeaux Institute in onCology (Inserm U1312 - BRIC), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre Hospitalier Le Mans (CH Le Mans), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Centre Hospitalier Victor Dupouy, Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Marseille, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Dynamic Microbiology - EA 7380 (DYNAMIC), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est (UPE)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CIC - CHU Henri Mondor, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience; BACKGROUND: Little is known about phototype and the response to systemic treatment in psoriasis. OBJECTIVE: To assess the characteristics of psoriasis, the therapeutic choice and its efficacy according to phototype. METHODS: We included patients from the PsoBioTeq cohort initiating a first biologic. Patients were classified according to their phototype. The evaluation included disease characteristics, choice of the initial biologic and therapeutic response at 12 months based on PASI 90 and DLQI 0/1. RESULTS: Of the 1400 patients included, 423 (30.2%), 904 (64.6%) and 73 (5.2%) were in the phototype I-II, III-IV and V-VI groups, respectively. The V-VI group had a higher initial DLQI, more frequently initiated ustekinumab. Patients in the phototype V-VI group maintained the first sequence of biologic as the other phototype groups, even though the proportion of patients reaching the PASI 90 and DLQI 0/1 at 12 months was lower in this group than other groups. CONCLUSION: Patient phototype seems associated with quality of life and choice of the initial biologic in psoriasis. Phototype V-VI group less frequently switched treatments than did the other groups when the response was not efficient.
Published: 2023

2. Omicron BA.1 breakthrough infection drives long-term remodeling of the memory B cell repertoire in vaccinated individuals

Author: Sokal, Aurélien, Barba-Spaeth, Giovanna, Hunault, Lise, Fernández, Ignacio, Broketa, Matteo, Meola, Annalisa, Fourati, Slim, Azzaoui, Imane, Vandenberghe, Alexis, Lagouge-Roussey, Pauline, Broutin, Manon, Roeser, Anais, Bouvier-Alias, Magali, Crickx, Etienne, Languille, Laetitia, Fournier, Morgane, Michel, Marc, Godeau, Bertrand, Gallien, Sébastien, Melica, Giovanna, Nguyen, Yann, Canoui-Poitrine, Florence, Noizat-Pirenne, France, Megret, Jérôme, Pawlotsky, Jean-Michel, Fillatreau, Simon, Reynaud, Claude-Agnès, Weill, Jean-Claude, Rey, Félix, Bruhns, Pierre, Mahévas, Matthieu, Chappert, Pascal, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Virologie Structurale - Structural Virology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Physiologie, physiopathologie et thérapeutique (ED 394), Sorbonne Université (SU), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Henri Mondor [Créteil], 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), Hôpital Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Cochin [AP-HP], IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Etablissement Français du Sang [Créteil], Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and This work was funded by the CAPNET (Comité ad-hoc de pilotage national des essaisthérapeutiques et autres recherches, French government) and by the Fondation PrincesseGrace. Assistance Publique – Hôpitaux de Paris (AP-HP, Département de la Recherche Cli-nique et du Développement) was the promotor and sponsor of MEMO-COV-2. Work in theUnit of Structural Virology was funded by Institut Pasteur, Urgence COVID-19 FundraisingCampaign of Institut Pasteur. PB acknowledges funding from the Institut Pasteur and InsitutNational de la Santé et de la Recherche Médicale (INSERM). AS was supported by a Posted’accueil from INSERM.
Subjects: [SDV]Life Sciences [q-bio], [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract: SummaryHow infection by a viral variant showing antigenic drift impacts a preformed mature human memory B cell (MBC) repertoire remains an open question. Here, we studied the MBC response up to 6 months after Omicron BA.1 breakthrough infection in individuals previously vaccinated with three doses of mRNA vaccine. Longitudinal analysis, using single-cell multi-omics and functional analysis of monoclonal antibodies from RBD-specific MBCs, revealed that a BA.1 breakthrough infection mostly recruited pre-existing cross-reactive MBCs with limitedde novoresponse against BA.1-restricted epitopes. Reorganization of clonal hierarchy and new rounds of germinal center reaction, however, combined to maintain diversity and induce progressive maturation of the MBC repertoire against common Hu-1 and BA.1, but not BA.5-restricted, SARS-CoV-2 Spike RBD epitopes. Such remodeling was further associated with marked improvement in overall neutralizing breadth and potency. These findings have fundamental implications for the design of future vaccination booster strategies.
Published: 2023

3. Update on French recommendations for the treatment of uncomplicated Neisseria gonorrhoeae infections

Author: Pierre Tattevin, Jean-Michel Molina, Charles Cazanave, Sébastien Fouéré, Cécile Bébéar, Béatrice Berçot, Nicolas Dupin, Marie Beylot-Barry, Agnès Riche, Olivier Chosidow, Marion Hélary, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], Laboratoire de Bactériologie EA 3671, Université Bordeaux Segalen - Bordeaux 2, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Bordeaux (UB), Service de maladies infectieuses et tropicales [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), 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), Service de dermatologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier d'Angoulême (CH Angoulême), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, None, 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 ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord
Subjects: Neisseria gonorrhoeae Infections, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], Public Health, Environmental and Occupational Health, MEDLINE, Dermatology, 3. Good health, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, Internal medicine, medicine, Pharmacology (medical), 030212 general & internal medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: Letter; International audience
Published: 2021

4. Post‐traumatic stress disorder in Stevens–Johnson syndrome and toxic epidermal necrolysis: prevalence and risk factors. A prospective study of 31 patients

Author: K. Zaghbib, Laurence Valeyrie-Allanore, K. Chazelas, L. Hefez, Pierre Wolkenstein, A. Colin, Saskia Ingen-Housz-Oro, T.-A. Duong, O. Chosidow, F. Bellivier, N. de Prost, Emilie Sbidian, H. Romano, M. Allain, Hôpital Henri Mondor, Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), CHU Tenon [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 Henri Mondor, 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), and VO, alexandra
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, Psychometrics, Population, Dermatology, Severity of Illness Index, Stress Disorders, Post-Traumatic, Young Adult, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Severity of illness, Prevalence, medicine, Humans, Medical history, Prospective Studies, Survivors, education, Prospective cohort study, Adverse effect, Aged, Retrospective Studies, education.field_of_study, business.industry, Traumatic stress, Retrospective cohort study, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, Middle Aged, medicine.disease, Toxic epidermal necrolysis, Hydroxyzine, Stevens-Johnson Syndrome, Acute Disease, Histamine H1 Antagonists, Female, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Follow-Up Studies
Abstract: International audience; Background: Epidermal necrolysis is a rare and severe cutaneous adverse reaction to drugs with long-term somatic consequences and potentially underrecognized psychological complications.Objectives: To assess the prevalence and risk factors of post-traumatic stress disorder (PTSD) in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in a population of adults undergoing psychiatric evaluation.Methods: In this prospective study, we included adult patients admitted at the acute phase of SJS/TEN to our dermatology department from June 2009 to February 2013. The main objective was to assess the prevalence of PTSD at 6 months after the acute disease phase, defined by a PTSD Checklist score > 44. Secondary objectives were to investigate risk factors of PTSD in the medical history of patients and characteristics of the disease at the acute phase by the Peritraumatic Dissociative Experience Questionnaire (PDEQ) and Peritraumatic Distress Inventory (PDI) and the degree of impairment on the Sheehan Disability Scale.Results: We initially included 32 of 80 patients admitted during the study period. At 6 months, seven of 30 still followed up had a PTSD Checklist score > 44, suggesting a PTSD prevalence of 23%; 23 (77%) patients had a hydroxyzine prescription at the acute phase. The main risk factors associated with PTSD at 6 months were psychological results at the acute phase.Conclusions: Despite frequent prescription of hydroxyzine at the acute phase, almost one-quarter of patients with SJS/TEN had PTSD at 6 months. A systematic psychiatric evaluation should be offered regularly for at least 1 year after the acute disease phase.
Published: 2018

5. T-piece versus pressure-support ventilation for spontaneous breathing trials before extubation in patients at high risk of reintubation: protocol for a multicentre, randomised controlled trial (TIP-EX)

Author: Jean-Paul Mira, Jeremy Bourenne, Agathe Delbove, René Robert, Gaetan Beduneau, Jean-Pierre Frat, Jérôme Devaquet, Arnaud Gacouin, Laurence Dangers, Nicolas Terzi, Stéphanie Ragot, Guylaine Labro, Antoine Romen, Gael Pradel, Christophe Leroy, Jean Reignier, Laurent Argaud, Rémi Coudroy, Quentin Levrat, Stephan Ehrmann, Jean-Pierre Quenot, Emmanuel Vivier, Guillaume Lacave, Christophe Guitton, Marie-Ange Azais, Alexandre Lautrette, Mai-Anh Nay, Anahita Rouzé, Damien Contou, Martin Dres, Gwenaël Prat, Jean Dellamonica, Arnaud W. Thille, Nicholas Sedillot, Béatrice Lacombe, Université de Lille, CNRS, Centre hospitalier universitaire de Poitiers [CHU Poitiers], CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Tours [CHRU Tours], Centre Hospitalier Victor Dupouy, Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Centre hospitalier de Pau, Centre Hospitalier Le Mans (CH Le Mans), Centre Hospitalier de Versailles André Mignot [CHV], CHU Dijon, CIC - CHU Henri Mondor, Centre Hospitalier Universitaire [Grenoble] [CHU], CHRU Brest - Service de Réanimation Médicale [CHU - BREST - Réa Med], Centre Hospitalier Emile Muller [Mulhouse] [CH E.Muller Mulhouse], Centre hospitalier universitaire de Nantes [CHU Nantes], Service d'anesthésie et réanimation chirurgicale [Nantes], Service de réanimation médicale [CHU Rouen], Centre Hospitalier Universitaire de Nice [CHU Nice], Centre Hospitalier Régional d'Orléans [CHRO], Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Centre hospitalier Bretagne Atlantique (Morbihan) [CHBA], Hôpital Cochin [AP-HP], Hôpital de la Timone [CHU - APHM] [TIMONE], Centre Jean Perrin [Clermont-Ferrand] [UNICANCER/CJP], Hôpital Edouard Herriot [CHU - HCL], Hôpital Foch [Suresnes], Centre hospitalier Saint Joseph - Saint Luc [Lyon], Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon [CHD Vendée], Centre Hospitalier Emile Roux [AP-HP], INSERM CIC 0802 [INSERM - CHU de Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire Félix-Guyon [Saint-Denis, La Réunion, France], Centre Hospitalier de Versailles André Mignot (CHV), Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Groupe Hospitalier Bretagne Sud (GHBS), Centre Hospitalier Henri Mondor d'Aurillac, Unité de soins intensifs médicaux [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Hypoxie : Physiopathologie Respiratoire et Cardiovasculaire (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CHRU Brest - Service de Réanimation Médicale (CHU - BREST - Réa Med), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpital Charles Nicolle [Rouen], Unité de Recherche Clinique de la Côte d’Azur [Nice] (URRIS UR2CA), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Centre Hospitalier Fleyriat [Bourg en Bresse], Unité de Soins Intensifs [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Hospices Civils de Lyon (HCL), Centre Hospitalier de La Rochelle (CHR), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), REVA research network, CarMeN, laboratoire, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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), CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche Clinique de la Côte d’Azur (URRIS UR2CA), Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: medicine.medical_treatment, [SDV]Life Sciences [q-bio], Pressure support ventilation, law.invention, Spontaneous breathing trial, Positive-Pressure Respiration, 03 medical and health sciences, Work of breathing, 0302 clinical medicine, Randomized controlled trial, law, Informed consent, medicine, respiratory medicine (see thoracic medicine), Humans, 030212 general & internal medicine, adult intensive & critical care, respiratory physiology, Mechanical ventilation, business.industry, Intensive Care, General Medicine, Intensive care unit, Respiration, Artificial, 3. Good health, [SDV] Life Sciences [q-bio], 030228 respiratory system, Anesthesia, Breathing, Airway Extubation, Medicine, France, business, Ventilator Weaning
Abstract: IntroductionIn intensive care unit (ICU), the decision of extubation is a critical time because mortality is particularly high in case of reintubation. To reduce that risk, guidelines recommend to systematically perform a spontaneous breathing trial (SBT) before extubation in order to mimic the postextubation physiological conditions. SBT is usually performed with a T-piece disconnecting the patient from the ventilator or with low levels of pressure-support ventilation (PSV). However, work of breathing is lower during PSV than during T-piece. Consequently, while PSV trial may hasten extubation, it may also increase the risk of reintubation. We hypothesise that, compared with T-piece, SBT performed using PSV may hasten extubation without increasing the risk of reintubation.Methods and analysisThis study is an investigator-initiated, multicentre randomised controlled trial comparing T-piece vs PSV for SBTs in patients at high risk of reintubation in ICUs. Nine hundred patients will be randomised with a 1:1 ratio in two groups according to the type of SBT. The primary outcome is the number of ventilator-free days at day 28, defined as the number of days alive and without invasive mechanical ventilation between the initial SBT (day 1) and day 28. Secondary outcomes include the number of days between the initial SBT and the first extubation attempt, weaning difficulty, the number of patients extubated after the initial SBT and not reintubated within the following 72 hours, the number of patients extubated within the 7 days following the initial SBT, the number of patients reintubated within the 7 days following extubation, in-ICU length of stay and mortality in ICU, at day 28 and at day 90.Ethics and disseminationThe study has been approved by the central ethics committee ‘Ile de France V’ (2019-A02151-56) and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT04227639.
Published: 2020

6. A Multilevel Functional Study of aSNAP25At-Risk Variant for Bipolar Disorder and Schizophrenia

Author: Franck Schürhoff, Pierre-Michel Llorca, Marc-Antoine d'Albis, Stéphane Jamain, Julia Linke, Marion Leboyer, Philippe Le Corvoisier, Josselin Houenou, Anne Dumaine, Cyril Poupon, Christophe Lançon, Andrei Szöke, Annabelle Henrion, Michèle Wessa, Nora Hamdani, Claire Daban, Jennifer Boisgontier, Bruno Etain, Caroline Barau, Marine Delavest, Douhairie, Marie-Laurence, IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Fondation FondaMental [Créteil], Pôle de Psychiatrie [Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital H. Mondor - A. Chenevier, Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neuropsychopharmacologie des addictions. Vulnérabilité et variabilité expérimentale et clinique (NAVVEC - UM 81 (UMR 8206/ U705)), Université Paris Diderot - Paris 7 (UPD7)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Clermont-Ferrand, Département Universitaire de Psychiatrie - [Hôpital Sainte Marguerite - APHM] (Hôpitaux Sud), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), 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), Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Laboratoire d'Imagerie et de Spectroscopie (LRMN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Department of General Psychiatry, Heidelberg University, Service de psychiatrie, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), CIC - CHU Henri Mondor, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: 0301 basic medicine, [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, brain imaging, Amygdala, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, Synaptic vesicle docking, medicine, genetics, Bipolar disorder, Allele, Prefrontal cortex, ComputingMilieux_MISCELLANEOUS, bipolar disorder, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SCCO.NEUR]Cognitive science/Neuroscience, General Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, SNAP25, medicine.disease, schizophrenia, 030104 developmental biology, medicine.anatomical_structure, SNARE, Cohort, Psychology, Neuroscience, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 030217 neurology & neurosurgery
Abstract: The synaptosomal-associated protein SNAP25 is a key player in synaptic vesicle docking and fusion and has been associated with multiple psychiatric conditions, including schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder. We recently identified a promoter variant inSNAP25,rs6039769, that is associated with early-onset bipolar disorder and a higher gene expression level in human prefrontal cortex. In the current study, we showed that this variant was associated both in males and females with schizophrenia in two independent cohorts. We then combinedin vitroandin vivoapproaches in humans to understand the functional impact of the at-risk allele. Thus, we showedin vitrothat thers6039769C allele was sufficient to increase theSNAP25transcription level. In a postmortem expression analysis of 33 individuals affected with schizophrenia and 30 unaffected control subjects, we showed that theSNAP25b/SNAP25aratio was increased in schizophrenic patients carrying thers6039769at-risk allele. Last, using genetics imaging in a cohort of 71 subjects, we showed that male risk carriers had an increased amygdala–ventromedial prefrontal cortex functional connectivity and a larger amygdala than non-risk carriers. The latter association has been replicated in an independent cohort of 121 independent subjects. Altogether, results from these multilevel functional studies are bringing strong evidence for the functional consequences of this allelic variation ofSNAP25on modulating the development and plasticity of the prefrontal–limbic network, which therefore may increase the vulnerability to both early-onset bipolar disorder and schizophrenia.SIGNIFICANCE STATEMENTFunctional characterization of disease-associated variants is a key challenge in understanding neuropsychiatric disorders and will open an avenue in the development of personalized treatments. Recent studies have accumulated evidence that the SNARE complex, and more specifically the SNAP25 protein, may be involved in psychiatric disorders. Here, our multilevel functional studies are bringing strong evidence for the functional consequences of an allelic variation ofSNAP25on modulating the development and plasticity of the prefrontal–limbic network. These results demonstrate a common genetically driven functional alteration of a synaptic mechanism both in schizophrenia and early-onset bipolar disorder and confirm the shared genetic vulnerability between these two disorders.
Published: 2017

7. A new human pyridinium metabolite of furosemide, inhibitor of mitochondrial complex I, is a candidate inducer of neurodegeneration

Author: Sonia Lehri-Boufala, Christophe Morin, Céline Laurencé, Michael Rivard, Philippe Le Corvoisier, Isabelle Lachaise, Thierry Martens, Laure Garrigue-Antar, Narimane Zeghbib, Caroline Barau, Institut de Chimie et des Matériaux Paris-Est (ICMPE), Institut de Chimie du CNRS (INC)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Service d'hépato-gastro-entérologie [APHP 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), 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), laboratoire Eau Environnement et Systèmes Urbains (LEESU), AgroParisTech-École des Ponts ParisTech (ENPC)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Centre National de la Recherche Scientifique (CNRS)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: 0301 basic medicine, Male, endocrine system diseases, [SDV]Life Sciences [q-bio], Metabolite, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Apoptosis, Pyridinium Compounds, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Mitochondrion, Pharmacology, Biochemistry, Nervous System, chemistry.chemical_compound, Mice, 0302 clinical medicine, Furosemide, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], ComputingMilieux_MISCELLANEOUS, Molecular Structure, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Chemistry, Neurodegeneration, Middle Aged, 3. Good health, Mitochondria, 030220 oncology & carcinogenesis, Toxicity, Female, medicine.symptom, medicine.drug, 03 medical and health sciences, Oxygen Consumption, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, In vivo, Cell Line, Tumor, medicine, Animals, Humans, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Aged, Electron Transport Complex I, Tyrosine hydroxylase, medicine.disease, 030104 developmental biology, Mechanism of action, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Reactive Oxygen Species
Abstract: International audience; Pharmaceuticals and their by-products are increasingly a matter of concern, because of their unknown impacts on human health and ecosystems. The lack of information on these transformation products, which toxicity may exceed that of their parent molecules, makes their detection and toxicological evaluation impossible.Recently we characterized the Pyridinium of furosemide (PoF), a new transformation product of furosemide, the most widely used diuretic and an emerging pollutant. Here, we reveal PoF toxicity in SH-SY5Y cells leading to alpha-synuclein accumulation, reactive oxygen species generation, and apoptosis. We also showed that its mechanism of action is mediated through specific inhibition of striatal respiratory chain complex I, both in vitro by direct exposure of striatum mitochondria to PoF, and in vivo, in striatal mitochondria isolated from mice exposed to PoF for 7 days in drinking water and sacrificed 30 days later. Moreover, in mice, PoF induced neurodegenerative diseases hallmarks like phospho-Serine129 alpha-synuclein, tyrosine hydroxylase decrease in striatum, Tau accumulation in hippocampus. Finally, we uncovered PoF as a new metabolite of furosemide present in urine of patients treated with this drug by LC/MS. As a physiopathologically relevant neurodegeneration inducer, this new metabolite warrants further studies in the framework of public health and environment protection.
Published: 2019

8. Immunoglobulin sub-class distribution in bipolar disorder and schizophrenia: potential relationship with latent Toxoplasma Gondii infection

Author: Hamdani, Nora, Bengoufa, Djaouida, Godin, Ophélia, Doukhan, Raphael, Le Guen, Emmanuel, Daban-Huard, Claire, Bennabi, Meriem, Delavest, Marine, Lépine, Jean-Pierre, Boukouaci, Wahid, Laouamri, Hakim, Houenou, Josselin, Jamain, Stéphane, Richard, Jean-Romain, Lecorvosier, Philippe, Yolken, Robert, Rajagopal, Krishnamoorthy, Leboyer, Marion, Tamouza, Ryad, 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), Pôle de Psychiatrie [Hôpital Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital H. Mondor - A. Chenevier, Fondation FondaMental [Créteil], Laboratoire Jean Dausset, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Alloimmunité-Autoimmunité-Transplantation (A2T), 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), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Commissariat à l'énergie atomique et aux énergies alternatives (CEA), 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), Johns Hopkins University Medical Center, This work was supported by ANR wich funded the study, INSERM and AP-HP and fondation fondamental institutional wich participate for the collection and analysis of data., and Duchange, Nathalie
Subjects: Adult, Male, Bipolar disorder, lcsh:RC435-571, MESH: Bipolar disorder, Humoral immunity, Immunoglobulins, Schizophrenia, Toxoplasma gondii, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Middle Aged, Young Adult, Risk Factors, Case-Control Studies, lcsh:Psychiatry, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, parasitic diseases, Humans, Female, Toxoplasma, Toxoplasmosis, Research Article
Abstract: International audience; BACKGROUND:Immune dysfunction could play a significant role in the pathogenesis of bipolar disorder (BD) and schizophrenia (SZ), conditions with an underlying pro-inflammatory state. Studies on humoral immune responses (which reflects antibody mediated fight against pathogens) in schizophrenia and bipolar disorder are sparse and often providing contradictory results. The aim of this study was to assess humoral immunity in a group of stable bipolar disorder and schizophrenia patients compared to controls by determining total Immunoglobulins and IgG subclasses and to assess their association with latent Toxoplasma gondii and/or CMV infection.METHODS:334 subjects (124 BD, 75 SZ and 135 Healthy Controls [HC]) were included and tested for humoral immunity by determining the total immunoglobulins (IgG,A and M) and IgG subclasses (IgG1, IgG2, IgG3, IgG4) and their relationship with latent Toxoplasma gondii infection, an established risk factor for BD and SZ.RESULTS:Although lower levels of IgG, IgG1, IgG2, IgG4 and IgA were found among BD as compared to HC and/or SZ, after adjustment for confounding variables, only low levels of IgG and IgG1 in BD remai- ned significant. Strikingly highest levels of antibodies to T. gondii (but not CMV) infection in BD and SZ were associated with lowest levels of IgG3 and IgG4 levels as compared to controls.CONCLUSIONS:Schizophrenia and bipolar disorder patients with latent T. gondii specific infection may be more vulnerable to changes in immuno-inflammatory processes than controls with similar latent infectious state. Simultaneous sequential immunological monitoring both in steady state and active disease phases in the same BD and SZ patients are warranted to understand the role of Toxoplasma gondii latency in these disorders.
Published: 2018

9. Percutaneous Left Atrial Appendage Closure Is a Reasonable Option for Patients With Atrial Fibrillation at High Risk for Cerebrovascular Events

Author: Emmanuel Teiger, Jean-Benoit Thambo, Pascal Defaye, Jean-Sylvain Hermida, Sélim Abbey, Didier Klug, Jean-Michel Juliard, Jean-Luc Pasquie, Gilles Rioufol, Antoine Lepillier, Meyer Elbaz, Jerome Horvilleur, Philippe Brenot, Bertrand Pierre, Philippe Le Corvoisier, Nicolas Amabile, Marian Andronache, Frederic Anselme, Sebastien Armero, Pierre Aubry, Etienne Audureau, Dominique Babuty, Babe Bakouboula, Clement Bars, Alban-Elouen Baruteau, Jacques Bille, Jean-Louis Bonnet, Francois Brigadeau, Eric Brochet, Sok-Sithikun Bun, Guillaume Cailla, Olivier Cesari, Didier Champagnac, Philippe Chevalier, Nicolas Combes, Bertrand Comet, Philippe Commeau, Jean-Claude Dearo, Antoine Dompnier, Bruno Farah, Philippe Garot, Daniel Gras, Cedric Giraudeau, Mathieu Granier, Patrice Guerin, Xavier Iriart, Zakaria Jalal, Laurence Jesel-Morel, Antoine Jeu, Priscille Kamtchueng, Nicolas Lellouche, Nicolas Meneveau, Norbert Nighoghossian, Akli Otmani, Remy Pelliere, Remy Pillière, Maxime Pons, Batric Popovic, Pénélope Pujadas, Roland Rossi, Antoine Roux, Yannick Saludas, Christian Spaulding, Victor Statiev, Julien Ternacle, Sarah Traulle, Pierre-François Winum, 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), Service cardiologie pédiatrique [Bordeaux], CHU Bordeaux [Bordeaux], Cardiac Stimulation and Rhythmology, CHU Grenoble, CHU Amiens-Picardie, Hôpital cardiologique, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Bichat - Claude Bernard, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Cardiovasculaire Louis Pradel, Hospices Civils de Lyon (HCL), Service de cardiologie [Toulouse], Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Griset SA, Diehl - Griset, and CIC - CHU Henri Mondor
Subjects: Male, medicine.medical_specialty, Cardiac Catheterization, anticoagulants, Percutaneous, Time Factors, Septal Occluder Device, [SDV]Life Sciences [q-bio], Population, Clinical Decision-Making, Atrial Appendage, Comorbidity, 030204 cardiovascular system & hematology, Prosthesis Design, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, atrial fibrillation, 030212 general & internal medicine, Prospective Studies, cardiovascular diseases, education, Stroke, Aged, education.field_of_study, cerebral hemorrhage, Interventional cardiology, business.industry, Incidence, atrial appendage, Atrial fibrillation, medicine.disease, stroke, 3. Good health, Clinical trial, Cerebrovascular Disorders, Treatment Outcome, Cardiology, Female, France, Cardiology and Cardiovascular Medicine, business
Abstract: Background— Percutaneous left atrial appendage (LAA) closure is an emerging option for patients with atrial fibrillation at high risk for cerebrovascular events. The multicenter FLAAC registry (French Nationwide Observational LAA Closure Registry) was established to assess LAA closure outcomes in everyday practice. Methods and Results— Four hundred thirty-six patients referred from April 2013 to September 2015 to 33 French interventional cardiology centers for percutaneous LAA closure were included prospectively in the FLAAC registry. Mean age was 75.4±0.4 years. The stroke risk was high (mean CHA 2 DS 2 –VASc score, 4.5±0.1) and most patients had experienced clinically significant bleeding (HAS-BLED score, 3.1±0.05). The device used was Amplatzer LAA occluder in 58% and the Watchman device in 42% of the patients. The procedural success rate was 98.4%. Median postprocedure follow-up was 12.0 (11.8–12.0) months and a single patient was lost to follow-up. During the periprocedural and subsequent follow-up period, procedure-related severe adverse events occurred in 21 (4.9%) and 10 (2.3%) patients, respectively. One-year cumulative incidences of ischemic stroke and cerebral hemorrhage were 2.9% (1.6–5.0) and 1.5% (0.7–3.2), respectively. Overall, 1-year mortality was 9.3% (6.9–12.5) with 7 of the 39 deaths related or possibly related to the device or procedure. Conclusions— This nationwide prospective registry shows that, in the French population, LAA closure is mainly used in patients with high comorbidity rates and a poor prognosis. LAA closure in such patients seems reasonable to decrease the stroke rate. The overall health status of these patients should be taken into account during the preprocedural evaluation process. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT02252861.
Published: 2018

10. 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

11. Factors associated with radiographic lesions in early axial spondyloarthritis. Results from the DESIR cohort

Author: Bijan Ghaleh, Aurélie Lethuaut, M. Blachier, Cécile Poulain, Valérie Farrenq, Bruno Fautrel, Pascal Claudepierre, Philippe Le Corvoisier, Salah Ferkal, Florence Canoui-Poitrine, Sylvie Bastuji-Garin, Maxime Dougados, Laboratoire d'Investigation Clinique (LIC), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Pôle Recherche Clinique-Santé Publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Service de rhumatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Rhumatologie, Université Paris Diderot - Paris 7 (UPD7), 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), 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 de rhumatologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri-Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Cochin [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12) - Institut National de la Santé et de la Recherche Médicale (INSERM) - IFR10, Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: MESH: Inflammation, Male, [SDV]Life Sciences [q-bio], Radiography, MESH : Sacroiliac Joint, MESH : Prospective Studies, Severity of Illness Index, MESH: Magnetic Resonance Imaging, Cohort Studies, 0302 clinical medicine, Epidemiology, MESH : Anti-Inflammatory Agents, Non-Steroidal, MESH : Female, Pharmacology (medical), Longitudinal Studies, Prospective Studies, MESH: Sacroiliac Joint, MESH: Longitudinal Studies, MESH: Cohort Studies, MESH : Longitudinal Studies, 0303 health sciences, MESH: Middle Aged, medicine.diagnostic_test, Anti-Inflammatory Agents, Non-Steroidal, MESH : Spondylarthritis, MESH : Adult, Middle Aged, MESH: Anti-Inflammatory Agents, Non-Steroidal, Magnetic Resonance Imaging, 3. Good health, [SDV] Life Sciences [q-bio], Cohort, MESH : Severity of Illness Index, Female, Radiology, MESH: Spine, Adult, medicine.medical_specialty, Alcohol Drinking, MESH : Male, MESH: Spondylarthritis, MESH : Cohort Studies, 03 medical and health sciences, Lumbar, Rheumatology, MESH : Magnetic Resonance Imaging, MESH: Severity of Illness Index, Spondylarthritis, MESH : Spine, medicine, Humans, MESH : Middle Aged, Spondylarthropathies, 030304 developmental biology, Inflammation, 030203 arthritis & rheumatology, Ankylosing spondylitis, MESH : Inflammation, MESH: Humans, business.industry, MESH : Humans, Sacroiliitis, MESH: Adult, Sacroiliac Joint, Magnetic resonance imaging, medicine.disease, MESH: Prospective Studies, MESH: Male, Spine, Surgery, MESH : Alcohol Drinking, business, MESH: Female, MESH: Alcohol Drinking
Abstract: International audience; OBJECTIVE: To assess whether factors such as inflammation by laboratory tests and MRI differ between early axial SpA with and without radiographic lesions. METHODS: Cross-sectional analysis of baseline data from Devenir des Spondylarthropathies Indifferenciées Récentes (DESIR) cohort patients having recent-onset inflammatory back pain and meeting Assessment of SpondyloArthritis international Society criteria. The baseline evaluation included radiographs and MRI of the SI joints (SIJs) and spine. Patients were classified as having radiographic lesions if they had at least one obvious sacroiliitis, grade 2 for at least one vertebral corner or grade 1 for at least two vertebral corners (at the cervical or lumbar level, according to the modified Stoke Ankylosing Spondylitis Spine Score). Associations between baseline characteristics and the presence of radiographic lesions were evaluated by estimating multi-adjusted odd ratios (aORs) and their 95% CIs using a logistic regression model. RESULTS: Of 475 patients, 180 (37.9%) had radiographic lesions. Factors positively associated with radiographic lesions were alcohol use (aOR 2.42; 95% CI 1.31, 4.44; P = 0.005), CRP level (aOR 1.44; 95% CI 1.13, 1.84; P = 0.003) and SIJ inflammation by MRI (aOR 2.25; 95% CI 1.40, 3.60; P = 0.001); negative associations occurred with good NSAID responsiveness (aOR 0.44; 95% CI 0.24, 0.81; P = 0.008); spinal MRI inflammation was associated with radiographic lesions only in smokers (aOR 1.99; 95% CI 1.01, 3.92; P = 0.048). CONCLUSION: Alcohol use, poor responsiveness to NSAIDs, CRP elevation, SIJ MRI inflammation and spinal MRI inflammation in smokers were independently associated with radiographic lesions in early axial SpA.
Published: 2013

12. Current aspects of the spectrum of acute heart failure syndromes in a real-life setting: the OFICA study

Author: Damien, Logeart, Richard, Isnard, Matthieu, Resche-Rigon, Marie-France, Seronde, Pascal, de Groote, Guillaume, Jondeau, Michel, Galinier, Geneviève, Mulak, Erwan, Donal, François, Delahaye, Yves, Juilliere, Thibaud, Damy, Patrick, Jourdain, Fabrice, Bauer, Jean-Christophe, Eicher, Yannick, Neuder, Jean-Noël, Trochu, Yaici, Khelil, Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, pharmacologie et physiopathologie des maladies cardiovasculaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de cardiologie, Hôpital Cardiologique-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Cardiologie [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Services de Pneumologie, Exploration Fonctionnelle Respiratoire et Cardiologie (Hôpital Louis Pradel), Hospices Civils de Lyon (HCL), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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), Pharmacologie des Dysfonctionnements Endotheliaux et Myocardiques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Cardiologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Radiopharmaceutiques biocliniques, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Heart Failure of the French Society of Cardiology, Biomarqueurs CArdioNeuroVASCulaires ( BioCANVAS ), Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( PCVP / CARDIO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Hôpital Cardiologique-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Hémostase, bio-ingénierie et remodelage cardiovasculaires ( LBPC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Galilée, Department of Cardiology, Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse], Laboratoire Traitement du Signal et de l'Image ( LTSI ), 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 ), Services de Pneumologie, Exploration Fonctionnelle Respiratoire et Cardiologie ( Hôpital Louis Pradel ), Hospices Civils de Lyon ( HCL ), Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), unité de recherche de l'institut du thorax UMR1087 UMR6291 ( ITX ), Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) (PCVP / CARDIO), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, Service de cardiologie [Toulouse], Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], 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), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, MESH: Registries, Hospital mortality, Cross-sectional study, MESH : Aged, [ SPI.SIGNAL ] Engineering Sciences [physics]/Signal and Image processing, MESH: Hospitalization, 030204 cardiovascular system & hematology, Severity of Illness Index, Medical Records, MESH : Cross-Sectional Studies, MESH: Aged, 80 and over, 0302 clinical medicine, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, Epidemiology, MESH : Female, Registries, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, 030212 general & internal medicine, MESH: Treatment Outcome, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, Ejection fraction, Medical record, MESH : Acute Disease, Middle Aged, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Health survey, 3. Good health, Hospitalization, Treatment Outcome, Acute Disease, MESH : Hospitalization, MESH: Acute Disease, Female, MESH : Severity of Illness Index, [SDV.IB]Life Sciences [q-bio]/Bioengineering, France, Cardiology and Cardiovascular Medicine, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, MESH: Medical Records, medicine.medical_specialty, [ INFO.INFO-TS ] Computer Science [cs]/Signal and Image Processing, MESH : Male, Heart failure, MESH : Treatment Outcome, Therapeutics, Guidelines, MESH : Hospital Mortality, 03 medical and health sciences, MESH: Cross-Sectional Studies, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH: Severity of Illness Index, Internal medicine, MESH : Medical Records, Severity of illness, medicine, Humans, MESH : Middle Aged, MESH: Hospital Mortality, MESH : Aged, 80 and over, MESH : France, Intensive care medicine, Aged, MESH: Humans, Aldosterone inhibitor, business.industry, MESH : Humans, medicine.disease, MESH: Male, MESH: France, Cross-Sectional Studies, Blood pressure, MESH: Heart Failure, MESH : Heart Failure, business, MESH: Female, MESH : Registries
Abstract: International audience; AIMS: To improve knowledge of epidemiological data, management, and clinical outcome of acute heart failure (AHF) in a real-life setting in France. METHODS AND RESULTS: We conducted an observational survey constituting a single-day snapshot of all unplanned hospitalizations because of AHF in 170 hospitals throughout France (the OFICA survey). A total of 1658 patients (median age 79 years, 55% male) were included. Family doctors were the first medical contact in 43% of cases, and patients were admitted through emergency departments in 64% of cases. Clinical scenarios were mainly acutely decompensated HF (48%) and acute pulmonary oedema (38%) with similar clinical and biological characteristics as well as outcome. Characteristics were different and severity higher in both shock and right HF. Infection and arrhythmia were the most frequent precipitating factors (27% and 24% of cases); diabetes and chronic pulmonary disease were the most frequent co-morbidities (31% and 21%). Over 80% of patients underwent both natriuretic peptide testing and echocardiography. LVEF was preserved (>50%) in 36% of patients and associated with specific characteristics and lower severity. Median hospital stay was 13 days; in-hospital mortality was 8.2%, and independent predictors were age, blood pressure, and creatinine. Treatment at discharge in patients with reduced LVEF included ACE inhibitors/ARBs, beta-blockers, and aldosterone inhibitors in 78, 67, and 27% cases. Non-surgical devices were reported in
Published: 2013

13. Functional status and co-morbidities are associated with in-hospital mortality among older patients with acute decompensated heart failure: a multicentre prospective cohort study

Author: Olivier Montagne, Isabelle Mahé, Jean-François Bergmann, Sylvie Bastuji-Garin, Herve Perchet, Dominique Mottier, Philippe Le Corvoisier, Bertrand Renaud, Elena Paillaud, 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), Laboratoire d'Investigation Clinique (LIC), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'Accueil des Urgences (Urgences - 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), Service de Médecine Interne (LOUIS MOURIER - Med Int), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Médecine Interne (DMI - Labiroisière), Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Département de Cardiologie - MEAUX, CH Meaux, Unité de médecine gériatrique (Gériatrie - Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)
Subjects: Male, Aging, Time Factors, Acute decompensated heart failure, Health Status, [SDV]Life Sciences [q-bio], Comorbidity, 030204 cardiovascular system & hematology, functional status, 0302 clinical medicine, Cognition, Interquartile range, Risk Factors, Odds Ratio, Prevalence, 030212 general & internal medicine, Hospital Mortality, Prospective Studies, Prospective cohort study, Aged, 80 and over, Age Factors, General Medicine, Prognosis, older patients, 3. Good health, Acute Disease, Cardiology, Female, France, Cohort study, medicine.medical_specialty, Acute coronary syndrome, acute decompensated heart failure, Renal function, Risk Assessment, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, medicine, Humans, Geriatric Assessment, Aged, Heart Failure, Inpatients, Chi-Square Distribution, business.industry, Odds ratio, medicine.disease, mortality, co-morbidities, Blood pressure, Logistic Models, Multivariate Analysis, Geriatrics and Gerontology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Among patients admitted for acute decompensated heart failure (ADHF), half are aged 75 years or over. The high prevalence of co-morbidities and functional impairments in this age group may affect patient outcomes. Objective To assess the association between co-morbidities, functional status and in-hospital mortality in patients with ADHF aged ≥75 years. Design A prospective, multicentre cohort study. Setting Five French hospitals. Subjects Five hundred and fifty-five patients aged ≥75 years admitted to the emergency department with ADHF. Methods Baseline clinical data and co-morbidities were recorded at admission. Functional status and cognition were assessed using the Katz index and Mini-Mental Status Examination score, respectively. The primary outcome was in-hospital mortality. Results We found high prevalences of co-morbidities and functional impairments including hypertension (74.0%), atrial fibrillation (40.2%), prior acute coronary syndrome (32.3%) and diabetes (18.2%). The average creatinine clearance was 56.3 ml/min/1.73 m(2) (interquartile range, 39.2-77.0). In-hospital mortality was 67/555 (12.1%; 95% confidence interval, 9.4-14.8). In multivariate analysis, in-hospital mortality showed a statistically positive association with prior loss of self-sufficiency (Odds ratio [OR]: 5.85 [2.25-12.19]), hyperglycaemia (OR: 1.80 [1.26-2.54] per 1 SD increase), prior cerebral ischaemic event (OR: 3.56 [1.51-8.44]) and troponin I elevation above upper limit of normal (OR: 2.81 [1.37-5.77]). In addition, systolic blood pressure (OR: 0.98 [0.97-0.99] per 1 mmHg increase) and creatinine clearance (OR: 0.72 [0.51-1.00] per 1 SD increase) were negatively associated with in-hospital mortality. Conclusion Co-morbidities and functional impairments are associated with a worse short-term prognosis in patients aged ≥75 years admitted for ADHF. Assessing these parameters at admission may improve patient management.
Published: 2015

14. Predictors of ventricular remodelling in patients with reperfused acute myocardial infarction and left ventricular dysfunction candidates for bone marrow cell therapy: insights from the BONAMI trial

Author: Alain Manrique, Jerome Roncalli, Christophe Piot, Alain Lebon, Claude Hossein-Foucher, Thierry Le Tourneau, Guillaume Lamirault, Béatrice Delasalle, Olivier Lairez, Patricia Lemarchand, Emmanuel Teiger, Marjorie Richardson, Catherine Sportouch-Duckan, Philippe Le Corvoisier, Yannick Neuder, Jean-Noël Trochu, Service de médecine nucléaire [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), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), 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), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CIC - Nantes, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), 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), Radiopharmaceutiques biocliniques, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plate-Forme de Recherche en Imagerie Cellulaire de Haute-Normandie (PRIMACEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-High-tech Research Infrastructures for Life Sciences (HeRacLeS), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Différenciation et communication neuronale et neuroendocrine (DC2N), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de cardiologie [Toulouse], Département de physiologie (CHU Henri Mondor), Hôpital Henri Mondor, Service de cardiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Troubles cognitifs vasculaires et dégénératifs, Université de Lille, Sciences et Technologies, 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), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Lemarchand, Patricia, Unité de recherche de l'institut du thorax (ITX-lab), Service Cardiologie [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Adult, Male, medicine.medical_specialty, Myocardial Infarction, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 030204 cardiovascular system & hematology, Article, 030218 nuclear medicine & medical imaging, Cell therapy, Ventricular Dysfunction, Left, 03 medical and health sciences, Myocardial perfusion imaging, 0302 clinical medicine, Radionuclide angiography, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Myocardial infarction, Ventricular remodeling, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Aged, Bone Marrow Transplantation, Tomography, Emission-Computed, Single-Photon, Ejection fraction, Ventricular Remodeling, medicine.diagnostic_test, business.industry, Myocardial Perfusion Imaging, General Medicine, Middle Aged, medicine.disease, Thallium Radioisotopes, Echocardiography, Cardiology, Female, Radiopharmaceuticals, business, Perfusion, Emission computed tomography
Abstract: Few data are available regarding the relation of left ventricular (LV) mechanical dyssynchrony to remodelling after acute myocardial infarction (MI) and stem cell therapy. We evaluated the 1-year time course of both LV mechanical dyssynchrony and remodelling in patients enrolled in the BONAMI trial, a randomized, multicenter controlled trial assessing cell therapy in patients with reperfused MI. Patients with acute MI and ejection fraction (EF) ≤ 45 % were randomized to cell therapy or to control and underwent thallium single-photon emission computed tomography (SPECT), radionuclide angiography, and echocardiography at baseline, 3 months, and 1 year. Eighty-three patients with a comprehensive 1-year follow-up were included. LV dyssynchrony was assessed by the standard deviation (SD) of the LV phase histogram using radionuclide angiography. Remodelling was defined as a 20 % increase in LV end-systolic volume index (LVESVI) at 1 year. At baseline, LVEF, wall motion score index, and perfusion defect size were significantly impaired in the 43 patients (52 %) with LV remodelling (all p
Published: 2015

15. Kawasaki disease in adults: observations in France and literature review Short title: Kawasaki disease in adults in France

Author: Fraison, Jean-Baptiste, Seve, Pascal, Dauphin, Claire, Mahr, Alfred, Gomard-Mennesson, Emeline, Varron, Loig, Pugnet, Gregory, Landron, Cédric, Roblot, Pascal, Oziol, Eric, Chalhoub, Gihane, Galempoix, Jean-Marc, Humbert, Sébastien, Humbert, Philippe, Sbidian, Emilie, Grange, Florent, Bayrou, Olivier, Cathebras, Pascal, Morlat, Philippe, Epaulard, Olivier, Pavese, Patricia, Du Boutin, Thi Huong, Zoulim, Abdelkader, Stankovic, Katia, Bachelez, Herve, Smail, Amar, Bachmeyer, C., Granel, Brigitte, Serratrice, Jacques, Brinchault, Graziella, Mekinian, Arsène, Costedoat-Chalumeau, Nathalie, Bourgarit-Durand, Anne, Puéchal, Xavier, Guillevin, Loïc, Piram, Maryam, Kone-Paut, Isabelle, Fain, Olivier, Jonchère, Laurent, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), 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), Service de Médecine Interne [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Médecine interne, Centre Hospitalier de Beziers, Centre Hospitalier de Montélimar, CH Montélimar, Service Médecine Interne et immunologie clinique [CHU Toulouse], Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service Médecine interne et immunopathologie clinique [CHU Toulouse], Pôle IUCT [CHU Toulouse], Service de Médecine Interne, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre Hospitalier de Charleville-Mezières, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), 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 Universitaire de Reims (CHU Reims), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Etienne-Hôpital Nord - Saint-Etienne, Service de médecine interne et maladies infectieuses [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, Department of infectious diseases, CHU Grenoble, Service des Maladies Infectieuses, CHU Pitié-Salpêtrière [AP-HP], Service de médecine interne [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), CHU Tenon [AP-HP], Service de Néphrologie - Médecine Interne, CHU Amiens-Picardie-hôpital Sud, Centre Hospitalier Creil, Hôpital Nord [CHU - APHM], Service de pneumologie [Rennes] = Pneumology [Rennes], CHU Pontchaillou [Rennes], Centre de référence des maladies autoimmunes et systémiques rares, 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), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pédiatrie Générale et Rhumatologie Pédiatrique, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service Pédiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de Médecine Interne, Centre Hospitalier Universitaire de Toulouse, PRES Université de Toulouse, Service de Néphrologie et Immunopathologie Clinique, Centre Hospitalier Universitaire de Toulouse, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), E14, Centre de Recherche en Cancérologie de Lyon ( 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 ) -Department of Internal Medicine, Hospices Civils de Lyon, Université de Lyon, Service de médecine interne, hôpital Gabriel-Montpied, CHU Clermont-Ferrand, Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Centre hospitalier régional Metz-Thionville ( CHR Metz-Thionville ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre Hospitalier Universitaire de Reims ( CHU Reims ), CHU Saint-Antoine [APHP], CHU Pitié-Salpêtrière [APHP], Service de médecine interne [Caen], Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -CHU Caen, CHU Tenon [APHP], CHU Amiens-Picardie-Hôpital Sud, Service de pneumologie, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CHU Pontchaillou [Rennes], Institut Cochin ( 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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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)-Department of Internal Medicine, Hospices Civils de Lyon, 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]), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and 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)
Subjects: Adult, [SDV] Life Sciences [q-bio], [ SDV ] Life Sciences [q-bio], intravenous immunoglobulin, [SDV]Life Sciences [q-bio], Mucocutaneous Lymph Node Syndrome
Abstract: International audience; Objective Kawasaki disease (KD) is a vasculitis that mostly occurs in young children and rarely in adults. We analyzed the characteristics of adult-onset KD (AKD) in France. Methods We collected retrospective and prospective data for patients with a diagnosis of KD occurring after the age of 18 years. Cases were obtained via various French medical networks and identified from the international literature. Results We included 43 patients of AKD at 26 institution from 1992 to 2015, with mean (SD) age 30 (11) years (range 18–68) and sex ratio (M/F) 1.2; 34 patients met the American Heart Association criteria and 9 were incomplete AKD. The median time to diagnosis was 13 days (interquartile range 8–21). The main symptoms were fever (100%), exanthema (98%), changes in the extremities (91%), conjunctivitis (77%), oral cavity changes (89%), cervical adenitis (55%) and cardiac abnormalities (45%). Overall, 35% of patients showed large-vessel vasculitis: coronary vasculitis (26%) and coronary aneurysm (19%). Treatment was mostly intravenous immunoglobulins (79%) and aspirin (81%). Four patients showed myocardial infarction due to coronary vasculitis, but none were treated with IVIg because of late diagnosis. After a median follow-up of 5 months (range 1–117), persistent aneurysm was noted in 9% of cases. Damage was significantly lower with early treatment than late or no treatment (p = 0.01). Conclusion Given the high frequency of cardiac involvement and complications in this series of AKD, diagnosis and treatment should not be delayed, and early IVIg treatment seems to improve the outcome
Published: 2015

16. Common and Rare Variant Analysis in Early-Onset Bipolar Disorder Vulnerability

Author: Liu, Chunyu, Cichon, Sven, Degenhardt, Franziska, Mattheisen, Manuel, Priebe, Lutz, Mathieu, Flavie, Kahn, Jean-Pierre, Henry, Chantal, Boland, Anne, Zelenika, Diana, Gut, Ivo, Heath, Simon, Etain, Bruno, Lathrop, Mark, Maier, Wolfgang, Albus, Margot, Rietschel, Marcella, Schulze, Thomas G., McMahon, Francis J., Kelsoe, John R., Hamshere, Marian, Craddock, Nicholas, Nöthen, Markus M., Mühleisen, Thomas, Bellivier, Frank, Leboyer, Marion, Georgi, Alexander, Zidane, Nora, Chevallier, Lucie, Deshommes, Jasmine, Nicolas, Aude, Henrion, Annabelle, 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), Fondation FondaMental [Créteil], Department of Genomics, Life and Brain Center, University of Bonn, Institute of Human Genetics, Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Division of Medical Genetics, University of Basel (Unibas), Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Department of Psychiatry, Plate-forme de Resources Biologiques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Albert Chenevier, 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), Department of Biomedicine and the Centre for Integrative Sequencing, Aarhus University [Aarhus], Service de Psychiatrie et Psychologie Clinique, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Hôpital Jeanne-d'Arc, Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centro Nacional de Análisi Genómico (CNAG), Centro Nacional de Análisis Genómico, Department of Psychiatry and Psychotherapy, Georg-August-University [Göttingen], Unit on the Genetic Basis of Mood and Anxiety Disorders, National Institutes of Health [Bethesda] (NIH), University of California [San Diego] (UC San Diego), University of California-University of California, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine [Cardiff], Cardiff University-Institute of Medical Genetics [Cardiff]-Cardiff University-Institute of Medical Genetics [Cardiff]-Medical Research Council (MRC), Pôle de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Medical Research Council (MRC)-School of Medicine [Cardiff], Institute of Medical Genetics [Cardiff]-Cardiff University-Institute of Medical Genetics [Cardiff]-Cardiff University, Guellaen, Georges, Georg-August-University = Georg-August-Universität Göttingen, University of California (UC)-University of California (UC), Cardiff University-Institute of Medical Genetics [Cardiff]-Cardiff University-Institute of Medical Genetics [Cardiff], Universität Bonn = University of Bonn, and University Hospital Mannheim | Universitätsmedizin Mannheim-University Hospital Mannheim | Universitätsmedizin Mannheim
Subjects: Male, Bipolar Disorder, lcsh:Medicine, Genome-wide association study, Disease, Bioinformatics, Cohort Studies, Chromosomal Disorders, Medicine and Health Sciences, Age of Onset, lcsh:Science, Genetics, Multidisciplinary, Genomics, 3. Good health, Meta-analysis, Medical genetics, Female, ddc:500, Research Article, medicine.medical_specialty, Biology, Bipolar disorder, Chromosomes, Genomic databases, Genotyping, Human genetics, Polymerase chain reaction, Polymorphism, Single Nucleotide, White People, Young Adult, Molecular genetics, Mental Health and Psychiatry, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Genome-Wide Association Studies, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetic Predisposition to Disease, Genetic Association Studies, Clinical Genetics, Mood Disorders, lcsh:R, Biology and Life Sciences, Computational Biology, Human Genetics, medicine.disease, Genome Analysis, R1, Genetics of Disease, RC0321, lcsh:Q, Age of onset, Genome-Wide Association Study
Abstract: The team of M. Leboyer is part of the École des Neurosciences de Paris Ile-de-France network, member of the Bio-Psy Labex and member of the European Network of Bipolar Research Expert Centres (ENBREC).; International audience; Bipolar disorder is one of the most common and devastating psychiatric disorders whose mechanisms remain largely unknown. Despite a strong genetic contribution demonstrated by twin and adoption studies, a polygenic background influences this multifactorial and heterogeneous psychiatric disorder. To identify susceptibility genes on a severe and more familial sub-form of the disease, we conducted a genome-wide association study focused on 211 patients of French origin with an early age at onset and 1,719 controls, and then replicated our data on a German sample of 159 patients with early-onset bipolar disorder and 998 controls. Replication study and subsequent meta-analysis revealed two genes encoding proteins involved in phosphoinositide signalling pathway (PLEKHA5 and PLCXD3). We performed additional replication studies in two datasets from the WTCCC (764 patients and 2,938 controls) and the GAIN-TGen cohorts (1,524 patients and 1,436 controls) and found nominal P-values both in the PLCXD3 and PLEKHA5 loci with the WTCCC sample. In addition, we identified in the French cohort one affected individual with a deletion at the PLCXD3 locus and another one carrying a missense variation in PLCXD3 (p.R93H), both supporting a role of the phosphatidylinositol pathway in early-onset bipolar disorder vulnerability. Although the current nominally significant findings should be interpreted with caution and need replication in independent cohorts, this study supports the strategy to combine genetic approaches to determine the molecular mechanisms underlying bipolar disorder.
Published: 2014

17. Early TNFα-antagonist therapy in everyday practice for inflammatory back pain suggesting axial spondyloarthritis: The DESIR cohort

Author: Canouï-Poitrine, Florence, Poulain, Cécile, Molto, Anna, Le Thuaut, Aurélie, Lafon, Cécile, Farrenq, Valérie, Ferkal, Salah, Le Corvoisier, Philippe, Ghaleh, Bijan, Bastuji-Garin, Sylvie, Fautrel, B., Dougados, Maxime, Claudepierre, Pascal, Laboratoire d'Investigation Clinique (LIC), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Pôle Recherche Clinique-Santé Publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Service de rhumatologie [CHU Henri Mondor], 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), 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 de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri-Mondor, Assistance publique - Hôpitaux de Paris (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), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12) - Institut National de la Santé et de la Recherche Médicale (INSERM) - IFR10, Service de Rhumatologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Cochin [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract: International audience; : Objective: To determine the frequency of, and factors associated with, early TNFα antagonist therapy in everyday clinical practice in patients with suspected axial spondyloarthropathy (ax-SpA). Methods: Prospective observational study in the French DESIR cohort of 708 patients with recent-onset (50 (OR, 1.88; 95%CI, 1.24;2.87; p=0.003), current or past disease-modifying antirheumatic drug use (OR, 2.09; 95%CI, 1.22;3.59; p=0.008), systemic corticosteroid use (OR, 2.48; 95%CI, 1.43;4.34; p=0.002), and mild to severe radiographic hip abnormalities (OR, 9.43; 95%CI, 2.11;42.09; p=0.003). After adjustment on these factors, Achilles enthesis hypervascularisation by power Doppler and number of workdays missed were associated with TNFα antagonist therapy. Conclusion: In DESIR cohort, about ¼ of patients with recent IBP suggestive of axSpA were under anti-TNFα therapy after one year of follow-up. All factors associated with this early initiation reflected higher disease activity, refractoriness, or severity, which suggests compliance of French rheumatologists with current treatment guidelines. © 2014 American College of Rheumatology.
Published: 2014

18. Role of natriuretic peptide to predict cardiac abnormalities in patients with hereditary transthyretin amyloidosis.: Cardiac biomarkers in FAP

Author: Damy, Thibaud, Deux, Jean-François, Moutereau, Stéphane, Guendouz, Soulef, Mohty, Dania, Rappeneau, Stéphane, Guellich, Aziz, Hittinger, Luc, Loric, Sylvain, Lefaucheur, Jean-Pascal, Plante-Bordeneuve, Violaine, INSERM U955, équipe 8, 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Service de Cardiologie [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-Réseau AMYLOSE Mondorien, Réseau AMYLOSE Mondorien-Réseau AMYLOSE Mondorien-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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), Réseau AMYLOSE Mondorien, Service de Radiologie [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 de Biochimie [Mondor], Service de cardiologie [CHU Limoges], CHU Limoges, INSERM U955, équipe 3, INSERM U955, équipe 7, Departement de Biochimie-Pharmacotoxicologie, 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)-Institut Mondor de Recherche Biomédicale (IMRB), Service de neurophysiologie [Mondor], Service de neurologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de neurologie [Mondor], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, and Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Hôpital Henri Mondor-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: MESH: Aged, MESH: Humans, MESH: Middle Aged, natriuretic peptide, troponin, cardiac amyloidosis, MESH: Adult, transthyretin, MESH: Male, echocardiography speckle tracking, MESH: Cardiomyopathies, MESH: Amyloid Neuropathies, Familial, MESH: Echocardiography, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, cardiovascular diseases, MESH: Troponin T, MESH: Natriuretic Peptide, Brain, MESH: Peptide Fragments, MESH: Female, cardiac markers
Abstract: International audience; BACKGROUND: Familial amyloid polyneuropathy (FAP) mainly targets the peripheral nervous system and heart. Early noninvasive detection of cardiac impairment is critical for therapeutic management. AIM: To assess if amino-terminal pro-brain natriuretic peptide (NT-proBNP) or troponin T (cTnT) can predict echocardiographic left-ventricle (LV) impairment in FAP. METHODS: Thirty-six asymptomatic carriers and patients with FAP had echocardiographic measurement of left-ventricular (LV) systolic function, hypertrophy (LVH) and estimation of filling pressure (FP). RESULTS: Overall, median age, NT-proBNP, and LV ejection fraction were, respectively, 59 years (41-74), 323 pg/ml (58-1960), and 60% (51-66). Twelve patients had increased cTnT. Prevalence of ATTR gene mutations was 53% for Val30Met. Four individuals were asymptomatic, 6 patients had isolated neurological clinical signs, and 26 had echo-LV abnormalities. The ROC curve identified NT-proBNP patients with echo-LV abnormalities (area: 0.92; (0.83-0.99), p = 0.001) at a threshold >82 pg/ml with a sensitivity of 92%, and a specificity of 90%. Increased in NT-proBNP occurred in patients with SD and/or LVH with or without increase in FP. Elevated cTnT (>0.01 ng/ml) was only observed in patients with LVH and systolic dysfunction, with or without FP. CONCLUSION: In FAP, NT-proBNP was associated with cardiac impairment suggesting that NT-proBNP could be used in carriers or in FAP patients with only neurologic symptoms for identifying the appropriate time to start cardiac echocardiographic assessment and follow-up. cTnT identified patients with severe cardiac disease.
Published: 2013

19. Ambulatory transradial percutaneous coronary intervention: A safe, effective, and cost-saving strategy.: Ambulatory PCI: a safe and effective strategy

Author: Le Corvoisier, Philippe, Gellen, Barnabas, Lesault, Pierre-François, Cohen, Remy, Champagne, Stéphane, Duval, Anne-Marie, Montalescot, Gilles, Elhadad, Simon, Montagne, Olivier, Durand-Zaleski, Isabelle, Dubois-Randé, Jean-Luc, Teiger, Emmanuel, Guellaen, Georges, 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), 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), Département de Cardiologie Interventionnelle, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Service de Cardiologie, Centre Hospitalier Lagny-Marne la Vallée, Fédération de Cardiologie, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Service de Santé Publique
Subjects: radial approach, safety, economic evaluation, percutaneous coronary intervention, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, ambulatory procedure, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, cardiovascular diseases
Abstract: International audience; Objectives: The aim of this prospective, multicenter study was to assess the safety, feasibility, acceptance, and cost of ambulatory transradial percutaneous coronary intervention (PCI) under the conditions of everyday practice. Background: Major advances in PCI techniques have considerably reduced the incidence of post-procedure complications. However, overnight admission still constitutes the standard of care in most interventional cardiology centers. Methods: Eligibility for ambulatory management was assessed in 370 patients with stable angina referred to three high-volume angioplasty centers. On the basis of pre-specified clinical and PCI-linked criteria, 220 patients were selected for ambulatory PCI. Results: The study population included a substantial proportion of patients with complex procedures: 115 (52.3%) patients with multivessel coronary artery disease, 50 (22.7%) patients with multilesion procedures, and 60 (21.5%) bifurcation lesions. After 4-6 hr observation period, 213 of the 220 patients (96.8%) were cleared for discharge. The remaining seven (3.2%) patients were kept overnight for unstable angina (n = 1), atypical chest discomfort (n = 2), puncture site hematoma (n = 1), or non-cardiovascular reasons (n = 3). Within 24 hr after discharge, no patients experienced readmission, stent occlusion, recurrent ischemia, or local complications. Furthermore, 99% of patients were satisfied with ambulatory management and 85% reported no anxiety. The average non-procedural cost was lower for ambulatory PCI than conventional PCI (1,230 ± 98 Euros vs. 2,304 ± 1814 Euros, P < 10(-6) ). Conclusions: Ambulatory PCI in patients with stable coronary artery disease is safe, effective, and well accepted by the patients. It may both significantly reduce costs and optimize hospital resource utilization. © 2012 Wiley Periodicals, Inc.
Published: 2013

20. Ambulatory transradial percutaneous coronary intervention: A safe, effective, and cost-saving strategy

Author: Le Corvoisier, Philippe, Gellen, Barnabas, Lesault, Pierre-François, Cohen, Remy, Champagne, Stéphane, Duval, Anne-Marie, Montalescot, Gilles, Elhadad, Simon, Montagne, Olivier, Durand-Zaleski, Isabelle, Dubois-Randé, Jean-Luc, Teiger, Emmanuel, 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), 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), Département de Cardiologie Interventionnelle, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Service de Cardiologie, Centre Hospitalier Lagny-Marne la Vallée, Fédération de Cardiologie, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Santé Publique, and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: radial approach, safety, economic evaluation, percutaneous coronary intervention, ambulatory procedure, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, cardiovascular diseases
Abstract: International audience; Objectives: The aim of this prospective, multicenter study was to assess the safety, feasibility, acceptance, and cost of ambulatory transradial percutaneous coronary intervention (PCI) under the conditions of everyday practice. Background: Major advances in PCI techniques have considerably reduced the incidence of post-procedure complications. However, overnight admission still constitutes the standard of care in most interventional cardiology centers. Methods: Eligibility for ambulatory management was assessed in 370 patients with stable angina referred to three high-volume angioplasty centers. On the basis of pre-specified clinical and PCI-linked criteria, 220 patients were selected for ambulatory PCI. Results: The study population included a substantial proportion of patients with complex procedures: 115 (52.3%) patients with multivessel coronary artery disease, 50 (22.7%) patients with multilesion procedures, and 60 (21.5%) bifurcation lesions. After 4-6 hr observation period, 213 of the 220 patients (96.8%) were cleared for discharge. The remaining seven (3.2%) patients were kept overnight for unstable angina (n = 1), atypical chest discomfort (n = 2), puncture site hematoma (n = 1), or non-cardiovascular reasons (n = 3). Within 24 hr after discharge, no patients experienced readmission, stent occlusion, recurrent ischemia, or local complications. Furthermore, 99% of patients were satisfied with ambulatory management and 85% reported no anxiety. The average non-procedural cost was lower for ambulatory PCI than conventional PCI (1,230 ± 98 Euros vs. 2,304 ± 1814 Euros, P < 10(-6) ). Conclusions: Ambulatory PCI in patients with stable coronary artery disease is safe, effective, and well accepted by the patients. It may both significantly reduce costs and optimize hospital resource utilization. © 2012 Wiley Periodicals, Inc.
Published: 2013

21. Évaluation économique prospective de la radiothérapie guidée par l'image des cancers de la prostate dans le cadre du programme national de soutien aux thérapeutiques innovantes et coûteuses. [Prospective economic evaluation of image-guided radiation therapy for prostate cancer in the framework of the national programme for innovative and costly therapies assessment.]

Author: Pommier, Pascal, Morelle, Magali, Perrier, Lionel, De Crevoisier, Renaud, Laplanche, A., Dudouet, Philippe, Mahé, Marc-André, Chauvet, Bruno, Nguyen, T.-D., Créhange, Gilles, Zawadi, Ayman, Chapet, O., Latorzeff, I., Bossi, Alberto, Beckendorf, Valérie, Touboul, Emmanuel, Muracciole, Xavier, Bachaud, Jean-Marc, Supiot, S., Lagrange, Jean Léon, Centre Léon Bérard [Lyon], CRLCC Eugène Marquis (CRLCC), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Département de Radiothérapie, Centre René Gauducheau-Centre de Lutte Contre le Cancer Nantes Atlantique 'René Gauducheau' (CLCC)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy (IGR), Centre Alexis Vautrin (CAV), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut Claudius Regaud, 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), Cette étude a reçu un financement de l'Institut national du cancer (Inca) dans le cadre du programme de soutien aux innovations diagnostiques et thérapeutiques coûteuses., Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Centre de Lutte Contre le Cancer Nantes Atlantique 'René Gauducheau' (CLCC), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Cone Beam CT, Microcosting, Fiduciels, Prostate, Radiothérapie guidée par l'image, Randomisée, [SDV.IB]Life Sciences [q-bio]/Bioengineering, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Coût, IGRT
Abstract: International audience; Purpose The main objective of the economical study was to prospectively and randomly assess the additional costs of daily versus weekly patient positioning quality control in image-guided radiotherapy (IGRT), taking into account the modalities of the 3D-imaging: tomography (CBCT) or gold seeds implants. A secondary objective was to prospectively assess the additional costs of 3D versus 2D imaging with portal imaging for patient positioning controls. Patients and methods Economics data are issued from a multicenter randomized medico-economics trial comparing the two frequencies of patient positioning control during prostate IGRT. A prospective cohort with patient positioning control with PI (control group) was constituted for the cost comparison between 3D (IGRT) versus 2D imaging. The economical evaluation was focused to the radiotherapy direct costs, adopting the hospital's point of view and using a microcosting method applied to the parameters that may lead to cost differences between evaluated strategies. Results The economical analysis included a total of 241 patients enrolled between 2007 and 2011 in seven centres, 183 in the randomized study (128 with CBCT and 55 with fiducial markers) and 58 in the control group. Compared to weekly controls, the average additional cost per patient of daily controls was €847 (CBCT) and €179 (markers). Compared to PI, the average additional cost per patient was €1392 (CBCT) and €997 (fiducial markers) for daily controls; €545 (CBCT) and €818 (markers) in case of weekly controls. Conclusion A daily frequency for image control in IGRT and 3D images patient positioning control (IGRT) for prostate cancer lead to significant additional cost compared to weekly control and 2D imaging (PI). Long-term clinical assessment will permit to assess the medico-economical ratio of these innovative radiotherapy modalities.
Published: 2012

22. Genetic and functional abnormalities of the melatonin biosynthesis pathway in patients with bipolar disorder

Author: Sarah Moreno, Marion Leboyer, Frank Bellivier, Sven Cichon, Bruno Etain, Stéphane Jamain, Cécile Pagan, Thomas W. Mühleisen, Flavie Mathieu, Jasmine Deshommes, Jean-Pierre Kahn, Thomas Bourgeron, Katia Le Dudal, Anne Dumaine, Khaled Moustafa, Jean-Marie Launay, Hany Goubran-Botros, Chantal Henry, Laetitia Francelle, Fondation FondaMental [Créteil], Psychiatrie génétique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Mondor de Recherche Biomédicale, Université Paris-Est (UPE), Gènes, Synapses et Cognition, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], 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 de Nancy (CHRU Nancy), University of Bonn, Research Center Juelich, This work was supported by the Institut Pasteur, the Institut National pour la Recherche Médicale (INSERM), the Assistance Publique des Hôpitaux de Paris (AP-HP), the Agence Nationale pour la Recherche (ANR – Project Manage_BPAD), the Fondation pour la Recherche sur le Cerveau (FRC), and the Réseau Thématique de Recherche et de Soin en Santé Mentale (Fondation FondaMental)., We thank the patients for participating in this study. We thank the cell bank of Cochin Hospital (J. Chelly). We thank C. Bouchier and S. Duthoy for the use of sequencing facilities at the Génopole Pasteur, B. Costes and N. Martin at the Genomic platform of the IMRB (M. Gossens), A. Hchikat, L. Margarit and G. Rouffet for technical assistance. We thank E. Abadie, C. Bulach, B. Cochet, M.J. Pereira Gomes, A. Raust, R. Cohen and O. Elgrabli-Wajsbrot for their assistance., ANR-06-NEURO-0026,MANAGE_BPAD,Approche multidisciplinaire incluant la génétique, la biochimie et la neuroimagerie pour l'exploration du trouble bipolaire(2006), Gènes, Synapses et Cognition (CNRS - UMR3571 ), 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), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), ANR-06-NEUR-0026,MANAGE_BPAS,Approche multidisciplinaire incluant la génétique, la biochimie et la neuroimagerie pour l'exploration du trouble bipolaire(2006), 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), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Universität Bonn = University of Bonn
Subjects: Male, Bipolar Disorder, Transcription, Genetic, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, [SCCO]Cognitive science, 0302 clinical medicine, Gene Frequency, MESH: Bipolar Disorder, Missense mutation, MESH: DNA Mutational Analysis, Promoter Regions, Genetic, Cells, Cultured, Genetics (clinical), Melatonin, MESH: Melatonin, MESH: Genetic Association Studies, MESH: Acetylserotonin O-Methyltransferase, MESH: Statistics, Nonparametric, MESH: Polymorphism, Single Nucleotide, MESH: Genetic Predisposition to Disease, General Medicine, MESH: Case-Control Studies, Female, medicine.drug, MESH: Cells, Cultured, Acetylserotonin O-Methyltransferase, medicine.medical_specialty, Mutation, Missense, Biology, Polymorphism, Single Nucleotide, Statistics, Nonparametric, 03 medical and health sciences, Internal medicine, MESH: Promoter Regions, Genetic, Genetics, medicine, MESH: Gene Frequency, Humans, Genetic Predisposition to Disease, Circadian rhythm, Bipolar disorder, Molecular Biology, Allele frequency, Gene, Genetic Association Studies, MESH: Mutation, Missense, MESH: Humans, Precursor Cells, B-Lymphoid, MESH: Transcription, Genetic, Haplotype, Case-control study, MESH: Haplotypes, medicine.disease, MESH: Male, 030227 psychiatry, Endocrinology, Haplotypes, MESH: Precursor Cells, B-Lymphoid, Case-Control Studies, MESH: Female, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Patients affected by bipolar disorder (BD) frequently report abnormalities in sleep/wake cycles. In addition, they showed abnormal oscillating melatonin secretion, a key regulator of circadian rhythms and sleep patterns. The acetylserotonin O-methyltransferase (ASMT) is a key enzyme of the melatonin biosynthesis and has recently been associated with psychiatric disorders such as autism spectrum disorders and depression. In this paper, we analysed rare and common variants of ASMT in patients with BD and unaffected control subjects and performed functional analysis of these variants by assaying the ASMT activity in their B-lymphoblastoid cell lines. We sequenced the coding and the regulatory regions of the gene in a discovery sample of 345 patients with BD and 220 controls. We performed an association study on this discovery sample using common variants located in the promoter region and showed that rs4446909 was significantly associated with BD (P= 0.01) and associated with a lower mRNA level (P< 10(-4)) and a lower enzymatic activity (P< 0.05) of ASMT. A replication study and a meta-analysis using 480 independent patients with BD and 672 controls confirmed the significant association between rs4446909 and BD (P= 0.002). These results correlate with the general lower ASMT enzymatic activity observed in patients with BD (P= 0.001) compared with controls. Finally, several deleterious ASMT mutations identified in patients were associated with low ASMT activity (P= 0.01). In this study, we determined how rare and common variations in ASMT might play a role in BD vulnerability and suggest a general role of melatonin as susceptibility factor for BD.
Published: 2012

23. Does the site of magnetic resonance imaging abnormalities match the site of recent-onset inflammatory back pain? The DESIR cohort

Author: Florence Canoui-Poitrine, Valérie Farrenq, M. Blachier, Cécile Poulain, Pascal Claudepierre, Bertrand Coutanceau, Bijan Ghaleh, Sylvie Bastuji-Garin, Alain Saraux, Philippe Le Corvoisier, Salah Ferkal, Maxime Dougados, Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Laboratoire d'Investigation Clinique (LIC), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Pôle Recherche Clinique-Santé Publique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Centre de référence des Neurofibromatoses, 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), 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)-IFR10, Service de rhumatologie [CHU Henri Mondor], Université Paris-Est Marne-la-Vallée (UPEM), Service de santé publique et d'épidémiologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Cochin [AP-HP], Université de Brest (UBO) - Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO) - IFR148, Assistance publique - Hôpitaux de Paris (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), Institut National de la Santé et de la Recherche Médicale (INSERM) - IFR10 - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor, and Université Paris-Sud - Paris 11 (UP11) - Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Bicêtre
Subjects: musculoskeletal diseases, Adult, Male, medicine.medical_specialty, Immunology, Lumbar vertebrae, General Biochemistry, Genetics and Molecular Biology, Thoracic Vertebrae, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Lumbar, Rheumatology, Spondylarthritis, Back pain, Immunology and Allergy, Medicine, Humans, 030212 general & internal medicine, Prospective Studies, 030203 arthritis & rheumatology, Sacroiliac joint, Ankylosing spondylitis, Lumbar Vertebrae, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Buttock Pain, Sacroiliac Joint, Middle Aged, medicine.disease, Low back pain, Magnetic Resonance Imaging, 3. Good health, Surgery, Radiography, medicine.anatomical_structure, Cross-Sectional Studies, Logistic Models, Back Pain, Thoracic vertebrae, Female, Radiology, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: ObjectivesTo assess whether the site of axial pain (thoracic spine, lumbar spine or buttock(s)) was associated with the site of MRI lesions in patients with recent inflammatory back pain (IBP) suggesting spondyloarthritis.MethodsWe conducted a cross-sectional study of baseline data in 708 patients with recent IBP from the DESIR cohort. Radiographs of the sacroiliac joints (SIJs) and MRI scans of the SIJs and thoracic and lumbar spine were obtained routinely. Associations between pain sites and sites of inflammatory and structural MRI changes were evaluated using separate multivariate logistic regressions.ResultsOf the 648 patients with complete data, 61% had thoracic pain, 91.6% lumbar pain and 79.2% buttock pain. MRI inflammation was seen in 19%, 21% and 46% of patients at the thoracic, lumbar and SIJ sites, respectively. By multivariate analysis, pain was significantly associated with MRI inflammation only at the same site (adjusted OR (aOR)thoracicpain1.71; 95% CI 1.09 to 2.67; p=0.02; aORlumbar pain2.53; 95% CI 1.03 to 6.20; p=0.04; aORbuttock pain2.86; 95% CI 1.84 to 4.46; pbuttock pain1.89; 95% CI 1.22 to 2.90; p=0.004). The association between pain site and site of MRI inflammation persisted in the subgroups with normal or doubtful SIJ radiographs or with Assessment of SpondyloArthritis international Society criteria for axial spondyloarthritis.ConclusionsThe site of pain (thoracic spine, lumbar spine or buttock(s)) is associated with MRI inflammation at the same site in patients with recent IBP.
Published: 2012

24. Waiting times before initiation of radiotherapy might not affect outcomes for patients with glioblastoma: a French retrospective analysis of patients treated in the era of concomitant temozolomide and radiotherapy

Author: Renaud de Crevoisier, Maud Aumont, Pierre Verrelle, Aymeri Huchet, Marie Pierre Sunyach, Christine Kerr, Sandrine Vinchon-Petit, Pierre Yves Bondiau, Jean Philippe Maire, Chantal Henzen, Fernand Missohou, Valérie Bernier, Xavier Durando, Georges Noël, Jean-Baptiste Clavier, Luc Taillandier, Philippe Collin, Emilie Le Rhun, A. d’Hombres, Jean Leon Lagrange, Loïc Feuvret, F. Thillays, Gilles Truc, D. Atlani, Centre Paul Strauss, CRLCC Paul Strauss, CHU Bordeaux [Bordeaux], Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Centre René Gauducheau, CRLCC René Gauducheau, Centre Léon Bérard [Lyon], CRLCC Eugène Marquis (CRLCC), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre Alexis Vautrin (CAV), Centre Paul Papin, CRLCC Paul Papin, 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), Service de Neuro-Oncologie [CHRU Nancy], and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Subjects: Male, Cancer Research, Multivariate analysis, Neurology, Time Factors, Survival, medicine.medical_treatment, MESH: Antineoplastic Agents, Alkylating, 0302 clinical medicine, MESH: Aged, 80 and over, MESH: Radiotherapy Dosage, MESH: Chemoradiotherapy, Aged, 80 and over, MESH: Aged, Univariate analysis, MESH: Middle Aged, Brain Neoplasms, MESH: Glioblastoma, Radiotherapy Dosage, Chemoradiotherapy, MESH: Follow-Up Studies, Middle Aged, Prognosis, 3. Good health, Dacarbazine, Survival Rate, Oncology, MESH: Waiting Lists, Chemotherapy, Adjuvant, MESH: Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, MESH: Brain Neoplasms, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], France, medicine.drug, Waiting time, Adult, medicine.medical_specialty, Waiting Lists, MESH: Survival Rate, Affect (psychology), Glioblastoma multiforme, MESH: Dacarbazine, MESH: Prognosis, 03 medical and health sciences, medicine, Temozolomide, Humans, Antineoplastic Agents, Alkylating, Aged, Retrospective Studies, MESH: Humans, Radiotherapy, business.industry, MESH: Time Factors, MESH: Adult, MESH: Retrospective Studies, MESH: Male, Surgery, Radiation therapy, MESH: France, Concomitant, Neurology (clinical), business, Glioblastoma, MESH: Female, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: International audience; Purpose of this study was to determine the effect of waiting time for radiotherapy on overall survival of patients with glioblastoma treated in the EORTC-NCIC trial at 18 centers in France. A total of 400 adult patients with glioblastoma who were treated between January 1, 2006 and December 31, 2006 were included. There were 282 patients with "minimum criteria" according to the EORTC-NCIC trial: (i) concurrent chemotherapy with temozolomide; and (ii) age between 18 and 70 years old. Among these patients, 229 were treated with adjuvant temozolomide and were classified as "maximal criteria". One-hundred and eighteen patients were in the "without minimal criteria" group. Waiting time from the first symptom (FS-RT), pathology diagnosis (P-RT), multidisciplinary meeting (MM-RT), surgery (S-RT), and CT scan for delineation (CT-RT) until the start of radiotherapy were recorded. Median follow-up for all patients was 327 days. Overall, median FS-RT, P-RT, MM-RT, CT-RT, and S-RT times were 77, 36, 32, 12, and 41 days, respectively. Median, and 12 and 24-month overall survival were 409 days, and 56.3 ± 2.1 % and 27.6 ± 2.6 %, respectively. Univariate analysis failed to reveal a difference in survival, irrespective of the delay. In multivariate analysis, independent favorable prognostic factors for overall survival were age (p ≤ 0.0001) and type of surgery (p = 0.0006). In this large series treated during the EORTC-NCIC protocol period, waiting time until radiotherapy did not seem to affect patient outcome.
Published: 2012

25. Molecular characteristics of Human Endogenous Retrovirus type-W in schizophrenia and bipolar disorder

Author: Perron, Hervé, Hamdani, Nora, Faucard, Raphaël, Lajnef, Mohamed, Jamain, Stéphane, Daban-Huard, Claire, Sarrazin, Samuel, Leguen, Emmanuel, Houenou, Josselin, Delavest, Marine, Moins-Teiserenc, Hélène, Bengoufa, Djaouida, Yolken, Robert, Madeira, Alexandra, Garcia-Montojo, Marta, Gehin, Nadège, Burgelin, Ingrid, Ollagnier, Guillaume, Bernard, Corinne, Dumaine, Anne, Henrion, Annabelle, Gombert, Anaïs, Le Dudal, Katia, Charron, Dominique, Krishnamoorthy, Rajagopal, Tamouza, Ryad, Leboyer, Marion, Guellaen, Georges, Geneuro, GeNeuro, Geneuro-Innovation, Université de Lyon, Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (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), Fondation FondaMental [Créteil], IFR49 - Neurospin - CEA, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hématologie -Immunologie -Cibles thérapeutiques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Stanley Laboratory of Developmental Neurovirology, Johns Hopkins University Medical Center, Plateforme de Ressources Biologiques, Stanley Research Program, 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), Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by the Institut National pour la Recherche Médicale (INSERM), France, the Assistance Publique des Hôpitaux de Paris (AP-HP) , France, and the Agence Nationale pour la Recherche (ANR - Project V .I.P.) , France and the Réseau Thématique de Recherche et de Soin en Santé Mentale, Fondation FondaMental, France.
Subjects: Bipolar Disorder, HERV-W, viruses, MSRV, embryonic structures, CNV, Schizophrenia, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Toxoplasma
Abstract: International audience; Epidemiological and genome-wide association studies of severe psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD), suggest complex interactions between multiple genetic elements and environmental factors. The involvement of genetic elements such as Human Endogenous Retroviruses type 'W' family (HERV-W) has consistently been associated with SZ. HERV-W envelope gene (env) is activated by environmental factors and encodes a protein displaying inflammation and neurotoxicity. The present study addressed the molecular characteristics of HERV-W env in SZ and BD. Hundred and thirty-six patients, 91 with BD, 45 with SZ and 73 healthy controls (HC) were included. HERV-W env transcription was found to be elevated in BD (P
Published: 2012

26. Molecular characteristics of Human Endogenous Retrovirus type-W in schizophrenia and bipolar disorder.: HERV-W in schizophrenia and bipolar disorder

Author: Perron, Hervé, Hamdani, Nora, Faucard, Raphaël, Lajnef, Mohamed, Jamain, Stéphane, Daban-Huard, Claire, Sarrazin, Samuel, Leguen, Emmanuel, Houenou, Josselin, Delavest, Marine, Moins-Teiserenc, Hélène, Bengoufa, Djaouida, Yolken, Robert, Madeira, Alexandra, Garcia-Montojo, Marta, Gehin, Nadège, Burgelin, Ingrid, Ollagnier, Guillaume, Bernard, Corinne, Dumaine, Anne, Henrion, Annabelle, Gombert, Anaïs, Le Dudal, Katia, Charron, Dominique, Krishnamoorthy, Rajagopal, Tamouza, Ryad, Leboyer, Marion, Geneuro, GeNeuro, Geneuro-Innovation, Université de Lyon, Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (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), Fondation FondaMental [Créteil], IFR49 - Neurospin - CEA, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hématologie -Immunologie -Cibles thérapeutiques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Stanley Laboratory of Developmental Neurovirology, Johns Hopkins University Medical Center, Plateforme de Ressources Biologiques, Stanley Research Program, 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), Dynamique des Structures et Interactions des Macromolécules Biologiques - Pôle de La Réunion (DSIMB Réunion), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by the Institut National pour la Recherche Médicale (INSERM), France, the Assistance Publique des Hôpitaux de Paris (AP-HP) , France, the Agence Nationale pour la Recherche (ANR - Project V .I.P.) , France and the Réseau Thématique de Recherche et de Soin en Santé Mentale, Fondation FondaMental, France., and Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)
Subjects: Bipolar Disorder, HERV-W, viruses, MSRV, embryonic structures, CNV, Schizophrenia, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Toxoplasma
Abstract: International audience; Epidemiological and genome-wide association studies of severe psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD), suggest complex interactions between multiple genetic elements and environmental factors. The involvement of genetic elements such as Human Endogenous Retroviruses type 'W' family (HERV-W) has consistently been associated with SZ. HERV-W envelope gene (env) is activated by environmental factors and encodes a protein displaying inflammation and neurotoxicity. The present study addressed the molecular characteristics of HERV-W env in SZ and BD. Hundred and thirty-six patients, 91 with BD, 45 with SZ and 73 healthy controls (HC) were included. HERV-W env transcription was found to be elevated in BD (P
Published: 2012

27. Intracoronary autologous mononucleated bone marrow cell infusion for acute myocardial infarction: results of the randomized multicenter BONAMI trial

Author: Emmanuel Teiger, Bernard Klein, Frédéric Mouquet, Jerome Roncalli, Guillaume Lamirault, Alain Manrique, Philippe Bourin, Yannick Neuder, Christophe Piot, Jean-Michel Nguyen, Michel Galinier, Eric Van Belle, Philippe Le Corvoisier, Marie-Jeanne Richard, Gérald Vanzetto, Dominique Crochet, Virginia Gaxotte, Sophie Susen, Anne-Sophie Polge, Hélène Rouard, Jean-Paul Beregi, Didier Carrié, Pierre Croisille, Béatrice Delasalle, Denis Agostini, Patricia Lemarchand, Thierry Le Tourneau, Angelo Parini, Jean-Noël Trochu, Catherine Sportouch, Fédération de Cardiologie, CHU Toulouse [Toulouse], Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Interface sang vaisseaux et réparation cardiovasculaire, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de recherche en biothérapie (IRB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Institut du thorax, Université de Nantes (UN)-IFR26-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), 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), Radiopharmaceutiques biocliniques, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe coeur et ischémie, 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), Therapies Interventionnelles Assistees Par l'Image et la Simulation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, 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), GIP Cyceron (Cyceron), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pôle de Pathologie cardiologie-vasculaire, Institut d'Hématologie-Transfusion-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-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 Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Thérapie Cellulaire [Grenoble], CHU Grenoble-EFS, Laboratoire de thérapie cellulaire (EFS), Etablissement Français du Sang, PIMESP, Université de Nantes (UN), PHRC national, AFM (téléthon), Fondation de France, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Therapies Interventionnelles Assistees Par l'Image et la Simulation - U 703 (Thiais), Fédération de Cardiologie [CHU Toulouse], Service Cardiologie [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-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 Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Lemarchand, Patricia, Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-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 Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Infarction, MESH: Magnetic Resonance Angiography, 030204 cardiovascular system & hematology, Coronary Angiography, MESH: Stroke Volume, law.invention, Ventricular Dysfunction, Left, 0302 clinical medicine, Randomized controlled trial, law, MESH: Ventricular Dysfunction, Left, Clinical endpoint, Medicine, MESH: Coronary Vessels, Myocardial infarction, MESH: Bone Marrow Transplantation, Bone Marrow Transplantation, MESH: Treatment Outcome, MESH: Aged, 0303 health sciences, Ejection fraction, MESH: Middle Aged, medicine.diagnostic_test, Smoking, Middle Aged, Coronary Vessels, MESH: Transplantation, Autologous, 3. Good health, MESH: Leukocytes, Mononuclear, MESH: Myocardial Infarction, Treatment Outcome, MESH: Young Adult, Cardiology, Female, Cardiology and Cardiovascular Medicine, Adult, medicine.medical_specialty, Adolescent, Cells, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Transplantation, Autologous, Article, MESH: Tomography, Emission-Computed, Single-Photon, Young Adult, 03 medical and health sciences, Radionuclide angiography, Reperfusion therapy, Internal medicine, Humans, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Aged, 030304 developmental biology, Tomography, Emission-Computed, Single-Photon, MESH: Adolescent, MESH: Humans, business.industry, Stroke Volume, MESH: Adult, medicine.disease, MESH: Male, MESH: Coronary Angiography, Transplantation, Leukocytes, Mononuclear, business, MESH: Female, Magnetic Resonance Angiography
Abstract: International audience; AIMS: Intracoronary administration of autologous bone marrow cells (BMCs) leads to a modest improvement in cardiac function, but the effect on myocardial viability is unknown. The aim of this randomized multicentre study was to evaluate the effect of BMC therapy on myocardial viability in patients with decreased left ventricular ejection fraction (LVEF) after acute myocardial infarction (AMI) and to identify predictive factors for improvement of myocardial viability. METHODS AND RESULTS: One hundred and one patients with AMI and successful reperfusion, LVEF ≤45%, and decreased myocardial viability (resting Tl201-SPECT) were randomized to either a control group (n = 49) or a BMC group (n = 52). Primary endpoint was improvement of myocardial viability 3 months after AMI. Baseline mean LVEF measured by radionuclide angiography was 36.3 ± 6.9%. Bone marrow cell infusion was performed 9.3 ± 1.7 days after AMI. Myocardial viability improved in 16/47 (34%) patients in the BMC group compared with 7/43 (16%) in the control group (P = 0.06). The number of non-viable segments becoming viable was 0.8 ± 1.1 in the control group and 1.2 ± 1.5 in the BMC group (P = 0.13). Multivariate analysis including major post-AMI prognostic factors showed a significant improvement of myocardial viability in BMC vs. control group (P = 0.03). Moreover, a significant adverse role for active smoking (P = 0.04) and a positive trend for microvascular obstruction (P = 0.07) were observed. CONCLUSION: Intracoronary autologous BMC administration to patients with decreased LVEF after AMI was associated with improvement of myocardial viability in multivariate-but not in univariate-analysis. A large multicentre international trial is warranted to further document the efficacy of cardiac cell therapy and better define a group of patients that will benefit from this therapy. Clinical Trial Registration Information: URL: http://www.clinicaltrials.gov. Unique identifier NCT00200707.
Published: 2011

28. Immune risk phenotype is associated with nosocomial lung infections in elderly in-patients

Author: C Brisacier, A. Plonquet, E Paillaud, Katia Ledudal, F Tahmasebi, JP Farcet, S Bastuji-Garin, Service d'immunologie biologique, 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, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Unité de recherche clinique, Service de médecine interne [Mondor], 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), This study was supported by the Soins Courants 2006 grant SCR06010 from the French Ministry of Health, Direction de la Recherche Clinique., and BMC, Ed.
Subjects: lcsh:Immunologic diseases. Allergy, Aging, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Clinical nutrition, lcsh:Geriatrics, elderly patients, 03 medical and health sciences, 0302 clinical medicine, Immunophenotyping, Immune system, medicine, Risk factor, 030304 developmental biology, immunosenescence, 0303 health sciences, Lung, biology, business.industry, Immune Risk Phenotype, Research, Immunosenescence, CMV status, Phenotype, 3. Good health, Ageing, lcsh:RC952-954.6, medicine.anatomical_structure, nosocomial infection, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antibody, business, lcsh:RC581-607, 030215 immunology
Abstract: Background Nosocomial infections are extremely common in the elderly and may be related to ageing of the immune system. The Immune Risk Phenotype (IRP), which predicts shorter survival in elderly patients, has not been evaluated as a possible risk factor for nosocomial infection. Our aim was to assess the prevalence of nosocomial infections in elderly in-patients and to investigate potential relationships between nosocomial infections and the immunophenotype, including IRP parameters. Results We included 252 consecutive in-patients aged 70 years or over (mean age, 85 ± 6.2 years), between 2006 and 2008. Among them, 97 experienced nosocomial infections, yielding a prevalence rate of 38.5% (95% confidence interval, 32.5-44.5). The main infection sites were the respiratory tract (21%) and urinary tract (17.1%) When we compared immunological parameters including cell counts determined by flow cytometry in the groups with and without nosocomial infections, we found that the group with nosocomial infections had significantly lower values for the CD4/CD8 ratio and naive CD8 and CD4 T-cell counts and higher counts of memory CD8 T-cells with a significant increase in CD28-negative CD8-T cells. Neither cytomegalovirus status (positive in 193/246 patients) nor presence of the IRP was associated with nosocomial infections. However, nosocomial pneumonia was significantly more common among IRP-positive patients than IRP-negative patients (17/60 versus 28/180; p = 0.036). Conclusion Immunological parameters that are easy to determine in everyday practice and known to be associated with immune system ageing and shorter survival in the elderly are also associated with an elevated risk of nosocomial pneumonia in the relatively short term.
Published: 2011

29. Mortality Associated with Neurofibromatosis 1: A Cohort Study of 1895 Patients in 1980-2006 in France

Author: Emilie Sbidian, Diana Rodriguez, Michel Zerah, Isabelle Kemlin, Laurence Valeyrie-Allanore, Tu Anh Duong, Sylvie Bastuji-Garin, Cédric Vialette, Smail Hadj-Rabia, Stanislas Lyonnet, Pierre Wolkenstein, Christophe Glorion, Salah Ferkal, BMC, Ed., Service de dermatologie [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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Laboratoire d'Investigation Clinique (LIC), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de référence des Neurofibromatoses, Unité Recherche Clinique, 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), Service de dermatologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de chirurgie orthopédique, Service de Génétique Médicale [CHU Necker], Service de Neurochirurgie, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), We thank ' Association Neurofibromatoses et Recklinghausen ' and ' Ligue française de lutte contre les Neurofibromatoses ' for them support for this study., 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, Laboratoire d'Investigation Clinique ( LIC ), Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de neuropédiatrie [Trousseau], CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, lcsh:Medicine, [SDV.GEN] Life Sciences [q-bio]/Genetics, Nerve Sheath Neoplasms, Cohort Studies, 0302 clinical medicine, Risk Factors, Cause of Death, Medicine, Genetics(clinical), Pharmacology (medical), Young adult, Child, Genetics (clinical), Cause of death, Medicine(all), Aged, 80 and over, 0303 health sciences, education.field_of_study, General Medicine, Middle Aged, 3. Good health, 030220 oncology & carcinogenesis, Child, Preschool, Cohort, Female, France, Cohort study, Adult, medicine.medical_specialty, Neurofibromatosis 1, Adolescent, Population, 03 medical and health sciences, Young Adult, Life Expectancy, Internal medicine, Genes, Neurofibromatosis 1, Humans, education, 030304 developmental biology, Aged, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Research, lcsh:R, Retrospective cohort study, Confidence interval, Standardized mortality ratio, business, [ SDV.GEN ] Life Sciences [q-bio]/Genetics
Abstract: Background Neurofibromatosis 1 (NF1), a common autosomal dominant disorder, was shown in one study to be associated with a 15-year decrease in life expectancy. However, data on mortality in NF1 are limited. Our aim was to evaluate mortality in a large retrospective cohort of NF1 patients seen in France between 1980 and 2006. Methods Consecutive NF1 patients referred to the National French Referral Center for Neurofibromatoses were included. The standardized mortality ratio (SMR) with its 95% confidence interval (CI) was calculated as the ratio of observed over expected numbers of deaths. We studied factors associated with death and causes of death. Results Between 1980 and 2006, 1895 NF1 patients were seen. Median follow-up was 6.8 years (range, 0.4-20.6). Vital status was available for 1226 (65%) patients, of whom 1159 (94.5%) survived and 67 (5.5%) died. Overall mortality was significantly increased in the NF1 cohort (SMR, 2.02; CI, 1.6-2.6; P < 10-4). The excess mortality occurred among patients aged 10 to 20 years (SMR, 5.2; CI, 2.6-9.3; P < 10-4) and 20 to 40 years (SMR, 4.1; 2.8-5.8; P < 10-4). Significant excess mortality was found in both males and females. In the 10-20 year age group, females had a significant increase in mortality compared to males (SMR, 12.6; CI, 5.7-23.9; and SMR, 1.8; CI, 0.2-6.4; respectively). The cause of death was available for 58 (86.6%) patients; malignant nerve sheath tumor was the main cause of death (60%). Conclusions We found significantly increased SMRs indicating excess mortality in NF1 patients compared to the general population. The definitive diagnosis of NF1 in all patients is a strength of our study, and the high rate of death related to malignant transformation is consistent with previous work. The retrospective design and hospital-based recruitment are limitations of our study. Mortality was significantly increased in NF1 patients aged 10 to 40 years and tended to be higher in females than in males.
Published: 2011

30. The cardiac renin-angiotensin system is responsible for high-salt diet-induced left ventricular hypertrophy in mice

Author: Bertrand Crozatier, Jinbo Su, Alain Berdeaux, Jean-Baptiste Michel, Philippe Le Corvoisier, C. Adamy, Luc Hittinger, Lucien Sambin, Fédération de Cardiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Henri Mondor-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), Signalisation et physiopathologie cardiaque, Université Paris-Sud - Paris 11 (UP11)-IFR141-Institut National de la Santé et de la Recherche Médicale (INSERM), Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by INSERM, the Université Paris-Est and the Société Française d'Hypertension Artérielle. This project was also supported by a grant from Bristol- Myers Squibb and Sanofi-Synthelabo laboratories., Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, and Guellaen, Georges
Subjects: Tetrazoles, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, Left ventricular hypertrophy, p38 Mitogen-Activated Protein Kinases, Renin-Angiotensin System, Mice, 0302 clinical medicine, Ramipril, Renin, Phosphorylation, Mitogen-activated protein kinases, Ultrasonography, 0303 health sciences, Immunohistochemistry, medicine.anatomical_structure, Blood pressure, Renin angiotensin system, Female, Hypertrophy, Left Ventricular, Cardiology and Cardiovascular Medicine, medicine.drug, medicine.medical_specialty, Heart Ventricles, Blotting, Western, Article, 03 medical and health sciences, Irbesartan, Internal medicine, Renin–angiotensin system, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Angiotensin II receptor type 1, business.industry, Biphenyl Compounds, JNK Mitogen-Activated Protein Kinases, Sodium, Dietary, medicine.disease, Fibrosis, Angiotensin II, Endocrinology, Ventricle, Heart failure, Autoradiography, business, High salt diet, Angiotensin II Type 1 Receptor Blockers
Abstract: International audience; AIMS: This study aimed to determine the role of the renin-angiotensin system (RAS) in high-salt (HS) diet-induced left ventricular hypertrophy (LVH). METHODS AND RESULTS: Swiss mice were subjected to regular salt (RS) diet (0.6% NaCl), HS diet (4% NaCl), and HS plus irbesartan (50 mg/kg/day) or ramipril (1 mg/kg/day). After 8 weeks, arterial pressure was similar in all groups and similar to baseline, whereas left ventricle/body weight ratio was higher in HS mice than in RS mice (P < 0.005). There were also significant increases in collagen density, angiotensin-converting enzyme activity, angiotensin II type 1 receptor (AT1 receptor) density, and extracellular signal-regulated kinase (ERK1/2) phosphorylation in the left ventricle. Interestingly, increases in wall thickness and ERK1 phosphorylation were more marked in the septum than in the rest of the left ventricle. Irbesartan or ramipril treatment prevented LVH and the increase in ERK phosphorylation and reduced collagen content and AT1 up-regulation but up-regulated AT2 receptors. CONCLUSION: In normal mice, HS diet induces septum-predominant LVH and fibrosis through activation of the cardiac RAS-ERK pathway, which can be blocked by irbesartan or ramipril, indicating a key role of the cardiac RAS in HS diet-induced LVH.
Published: 2010

31. [Image guided radiation therapy (IGRT)]

Author: Lagrange, Jean Léon, De Crevoisier, Renaud, 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), Laboratoire Traitement du Signal et de l'Image (LTSI), 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), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: radiothérapie guidée par l'image, Male, Lung Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Imaging, Three-Dimensional, MESH: Radiotherapy, Computer-Assisted, Imaging, Three-Dimensional, Neoplasms, Humans, MESH: Neoplasms, Four-Dimensional Computed Tomography, MESH: Otorhinolaryngologic Neoplasms, Ultrasonography, MESH: Humans, Spinal Neoplasms, MESH: Four-Dimensional Computed Tomography, Brain Neoplasms, Prostatic Neoplasms, variation anatomique, MESH: Radiotherapy, Intensity-Modulated, MESH: Spinal Neoplasms, MESH: Male, Radiotherapy, Computer-Assisted, MESH: Lung Neoplasms, Otorhinolaryngologic Neoplasms, MESH: Prostatic Neoplasms, MESH: Brain Neoplasms, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Radiotherapy, Intensity-Modulated, MESH: Ultrasonography
Abstract: International audience; Image guided radiation therapy (IGRT) is a major technical innovation of radiotherapy. It allows locating the tumor under the linear accelerator just before the irradiation, by direct visualization (3D mode soft tissue) or indirect visualization (2D mode and radio-opaque markers). The technical implementation of IGRT is done by very different complex devices. The most common modality, because available in any new accelerator, is the cone beam CT. The main experiment of IGRT focuses on prostate cancer. Preliminary studies suggest the use of IGRT combined with IMRT should increase local control and decrease toxicity, especially rectal toxicity. In head and neck tumors, due to major deformation, a rigid registration is insufficient and replanning is necessary (adaptive radiotherapy). The onboard imaging delivers a specific dose, needed to be measured and taken into account, in order not to increase the risk of toxicity. Studies comparing different modalities of IGRT according to clinical and economic endpoints are ongoing; to better define the therapeutic indications.
Published: 2010

32. NF1 microdeletions in neurofibromatosis type 1: from genotype to phenotype

Author: Dominique Vidaud, Michel Vidaud, Jean Soulier, Marc Sanson, Eric Pasmant, Marie-José Hamel, Meena Upadhyaya, Sébastien Barbarot, Hélène Dollfus, Salah Ferkal, Gillian Spurlock, Béatrice Parfait, Anne Dieux-Coeslier, Bertrand Isidor, Ingrid Laurendeau, Audrey Sabbagh, Elisa Grillo, Diana Rodriguez, Ivan Bièche, Ludovic Martin, Didier Lacombe, Pierre Wolkenstein, Laurent Pasquier, B. Leheup, Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux ( Inserm U745 ), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Medical Genetics, Institute of Medical Genetics, Service de Biochimie et Génétique Moléculaire, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Department of Dermatology, Université d'Angers ( UA ), Service de Dermatologie, Hôtel Dieu, CHU de Nantes, Service de Médecine Infantile III et Génétique Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Affections de la Myeline et des Canaux Ioniques Musculaires, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Pellegrin Hospital, Laboratoire de Génétique Médicale EA 3949, Faculté de Médecine de Strasbourg, Université de Strasbourg, Génétique et Développement, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR97-Centre National de la Recherche Scientifique ( CNRS ), Service de Génétique Médicale, 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 ), 3UMR728 INSERM Unité d'immuno-hématologie (UIH) and laboratoire d'hématologie, Hôpital St-Louis, AP-HP, Département de neurologie 2 - Mazarin, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Center for Clinical Genetics, Hôpital Jeanne de Flandre [Lille], Service de dermatologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Cardiff University, Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux (Inserm U745), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Université d'Angers (UA), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Génétique Médicale (LGM), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR97-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), UPMC - Département de neurologie 2 - Mazarin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-IFR97-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: Adult, Male, congenital, hereditary, and neonatal diseases and abnormalities, Neurofibromatosis 1, Genotype, [SDV]Life Sciences [q-bio], Biology, medicine.disease_cause, Contiguous gene syndrome, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Genetics, medicine, Humans, Genetic Predisposition to Disease, Neurofibromatosis, 10. No inequality, neoplasms, Genetic Association Studies, Genetics (clinical), Sequence Deletion, 030304 developmental biology, Comparative Genomic Hybridization, 0303 health sciences, Mutation, Neurofibromin 1, [ SDV ] Life Sciences [q-bio], Gene Expression Profiling, Breakpoint, Life Sciences, Middle Aged, medicine.disease, Phenotype, eye diseases, nervous system diseases, Gene expression profiling, Regression Analysis, Female, 030217 neurology & neurosurgery, Comparative genomic hybridization
Abstract: International audience; In 5-10% of patients, neurofibromatosis type 1 (NF1) results from microdeletions that encompass the entire NF1 gene and a variable number of flanking genes. Two recurrent microdeletion types are found in most cases, with microdeletion breakpoints located in paralogous regions flanking NF1 (proximal NF1-REP-a and distal NF1-REP–c for the 1.4 Mb type-1 microdeletion, and SUZ12 and SUZ12P for the 1.2 Mb type-2 microdeletion). A more severe phenotype is usually associated with NF1 microdeletion patients than in those with intragenic mutations. We characterized NF1 microdeletions in 70 unrelated NF1 microdeleted patients using a high-resolution NF1 custom array comparative genomic hybridization (CGH). Genotype-phenotype correlations were studied in 58 of these microdeletion patients and compared to 389 patients with intragenic truncating NF1 mutations and phenotyped in the same standardized way. Our results confirmed in an unbiased manner the existence of a contiguous gene syndrome with a significantly higher incidence of learning disabilities and facial dysmorphism in microdeleted patients compared to patients with intragenic NF1 mutations. Microdeleted NF1 patients also showed a trend toward significance for childhood overgrowth. High-resolution array-CGH identified a new recurrent ~1.0 Mb microdeletion type, designated as type-3, with breakpoints in the paralogous regions middle NF1-REP-b and distal NF1-REP–c.
Published: 2010

33. Role for interleukin-6 in COPD-related pulmonary hypertension

Author: Laurent Savale, Bernard Maitre, Saadia Eddahibi, Philippe Le Corvoisier, Ly Tu, Serge Adnot, Christian Brandt, Christos Chouaid, Emmanuel Weitzenblum, Bruno Housset, Matthieu Canuet, Benjamin Sztrymf, Ari Chaouat, Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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 de chirurgie thoracique et d'anatomopathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Hôtel Dieu, Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique, Centre Chirurgical Marie Lannelongue (CCML)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11), Service de Pneumologie et de Pathologie Professionnelle, CHI Créteil, 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), Service de pneumologie, CHU Strasbourg-Hopital Civil, Chaouat A, L Savale, E Weitzenblum, S Eddahibi, S Adnot ., C Chouaid, L Tu, B Sztrymf, M Canuet, B Maitre, B Housset, C Brandt, Le P Corvoisier, and Centre chirurgical Marie Lannelongue-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Pathology, MESH: Chi-Square Distribution, Interleukin-1beta, Gene Expression, MESH: Pulmonary Disease, Chronic Obstructive, MESH: Respiratory Function Tests, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Gastroenterology, MESH: Regression Analysis, Pulmonary function testing, MESH: Genotype, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, MESH: Interleukin-1beta, Chemokine CCL2, MESH: Aged, 0303 health sciences, COPD, MESH: Statistics, Nonparametric, MESH: Middle Aged, Respiratory disease, Interleukin, MESH: Enzyme-Linked Immunosorbent Assay, Middle Aged, MESH: Case-Control Studies, 3. Good health, Respiratory Function Tests, Circulatory system, Regression Analysis, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, MESH: Gene Expression, Genotype, Hypertension, Pulmonary, Enzyme-Linked Immunosorbent Assay, Statistics, Nonparametric, 03 medical and health sciences, Internal medicine, medicine.artery, MESH: Polymorphism, Genetic, medicine, Humans, MESH: Chemokine CCL2, 030304 developmental biology, Aged, Chi-Square Distribution, Polymorphism, Genetic, MESH: Humans, MESH: Hypertension, Pulmonary, business.industry, Interleukin-6, MESH: Adult, Hypoxia (medical), medicine.disease, Pulmonary hypertension, MESH: Interleukin-6, MESH: Male, Case-Control Studies, Pulmonary artery, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female
Abstract: International audience; BACKGROUND: Pulmonary artery remodeling triggered by alveolar hypoxia is considered the main mechanism of pulmonary hypertension (PH) in COPD patients. We hypothesized that the risk for PH in COPD is increased by an elevation in the proinflammatory cytokines interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), and IL-1beta, as well as by specific genetic polymorphisms of these cytokines. METHODS: We assessed cytokine plasma levels and the polymorphisms G(-174)C IL-6, C(-511)T IL-1beta, and A(-2518)G MCP-1 in 148 COPD patients (recruited at two centers) with right heart catheterization data and 180 control subjects including smokers and nonsmokers. Human pulmonary artery smooth muscle cells (PA-SMCs) were cultured for IL-6 messenger RNA assays under normoxic and hypoxic conditions. RESULTS: Patients with PH (mean pulmonary artery pressure [PAP], >or= 25 mm Hg) had lower Pao(2) and higher plasma IL-6 values than those without PH; there were no differences in terms of pulmonary function test results or CT scan emphysema scores. Plasma IL-6 correlated with mean PAP (r = 0.39; p < 0.001) and was included in a multiple stepwise regression analysis, with mean PAP as the dependent variable. In patients with the IL-6 GG genotype, the mean PAP value was significantly higher and PH was more common than in CG or CC patients (adjusted odds ratio, 4.32; 95% confidence interval, 1.96 to 9.54). Exposure to 4 h of hypoxia led to an about twofold increase in IL-6 messenger RNA in cultured human PA-SMCs. CONCLUSIONS: Inflammation, most likely involving IL-6, may contribute substantially to PH complicating COPD.
Published: 2009

34. Glutathione deficiency in cardiac patients is related to the functional status and structural cardiac abnormalities

Author: Françoise Pecker, Jean-Luc Dubois-Randé, Luc Hittinger, Philippe Caramelle, Thibaud Damy, M. Kirsch, Lara Khouzami, Philippe Le Corvoisier, Françoise Roudot-Thoraval, Catherine Pavoine, Fédération de cardiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-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)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, 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), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Guellaen, Georges
Subjects: Male, Cardiovascular Disorders/Heart Failure, Cardiomyopathy, lcsh:Medicine, 030204 cardiovascular system & hematology, Severity of Illness Index, Coronary artery disease, Ventricular Dysfunction, Left, chemistry.chemical_compound, 0302 clinical medicine, MESH: Ventricular Dysfunction, Left, lcsh:Science, MESH: Aged, MESH: Glutathione, 0303 health sciences, MESH: Middle Aged, Multidisciplinary, Atrial fibrillation, Venous blood, Middle Aged, Glutathione, MESH: Case-Control Studies, 3. Good health, Cardiac surgery, Cardiovascular Diseases, Cardiology, cardiovascular system, Female, medicine.symptom, Research Article, Adult, Heart Defects, Congenital, medicine.medical_specialty, MESH: Myocardium, Cardiovascular Disorders, Asymptomatic, 03 medical and health sciences, MESH: Severity of Illness Index, Internal medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, Cardiovascular Disorders/Congenital Heart Disease, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Heart Atria, Aged, 030304 developmental biology, MESH: Humans, business.industry, Myocardium, lcsh:R, MESH: Cardiovascular Diseases, MESH: Adult, MESH: Heart Defects, Congenital, medicine.disease, MESH: Male, chemistry, Case-Control Studies, Heart failure, MESH: Heart Atria, lcsh:Q, business, MESH: Female
Abstract: International audience; BACKGROUND: The tripeptide glutathione (L-gamma-glutamyl-cysteinyl-glycine) is essential to cell survival, and deficiency in cardiac and systemic glutathione relates to heart failure progression and cardiac remodelling in animal models. Accordingly, we investigated cardiac and blood glutathione levels in patients of different functional classes and with different structural heart diseases. METHODS: Glutathione was measured using standard enzymatic recycling method in venous blood samples obtained from 91 individuals, including 15 healthy volunteers and 76 patients of New York Heart Association (NYHA) functional class I to IV, undergoing cardiac surgery for coronary artery disease, aortic stenosis or terminal cardiomyopathy. Glutathione was also quantified in right atrial appendages obtained at the time of surgery. RESULTS: In atrial tissue, glutathione was severely depleted (-58%) in NYHA class IV patients compared to NYHA class I patients (P = 0.002). In patients with coronary artery disease, this depletion was related to the severity of left ventricular dysfunction (P = 0.006). Compared to healthy controls, blood glutathione was decreased by 21% in NYHA class I patients with structural cardiac disease (P
Published: 2009

35. [The Clinical Investigation Centers in France: Whatzat? What for? How does it work?]

Author: Montagne, Olivier, Le Corvoisier, Philippe, 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), and Montagne, Olivier
Subjects: [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Hospitals, University, Clinical Trials as Topic, Universities, Research, therapeutics, Humans, Industry, Biomedical research, France, quality control, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, ethics
Abstract: International audience; For the last 15 years, French university-affiliated hospitals have dramatically modified how biomedical research is conducted in France. Multidisciplinary and technically complex research projects are increasingly difficult to conduct in clinical units. To ensure quality, good clinical practice, and security, platforms dedicated to clinical research with specific staff have been implanted. These units, called Clinical Investigation Centers (CICs), are open to academic and industrial investigators working in the medical fields involving patients and healthy volunteers. The CICs' activities are always closely related to the university hospital research programs and can also serve as a tool for locally implanted clinical and fundamental research teams (INSERM). Nowadays, clinical research requires specific tools and platforms. To enhance French university hospital research efficiency and provide a more open research environment, all investigators, on-site as well as from other institutions, are invited to use these cohesive research facilities and skills to conduct protocols that are fully adapted to their needs in optimal conditions of professional clinical research.
Published: 2008

36. Neutral sphingomyelinase inhibition participates to the benefits of N-acetylcysteine treatment in post-myocardial infarction failing heart rats

Author: Adamy, Christophe, Mulder, Paul, Khouzami, Lara, Andrieu-Abadie, Nathalie, Defer, Nicole, Candiani, Gabriele, Pavoine, Catherine, Caramelle, Philippe, Souktani, Richard, Le Corvoisier, Philippe, Perier, Magali, Kirsch, Matthias, Damy, Thibaud, Berdeaux, Alain, Levade, Thierry, Thuillez, Christian, Hittinger, Luc, Pecker, Françoise, 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), Institut Mondor de médecine moléculaire (Im3), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Pharmacologie des Dysfonctionnements Endotheliaux et Myocardiques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - CHU Henri Mondor, Fédération de cardiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Guellaen, Georges
Subjects: [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, neutral sphingomyelinase, tumor necrosis factor-alpha, glutathione, N-acetylcysteine, chronic heart failure, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: Deficiency in cellular thiol tripeptide glutathione (l-gamma glutamyl-cysteinyl-glycine) determines the severity of several chronic and inflammatory human diseases that may be relieved by oral treatment with the glutathione precursor N-acetylcysteine (NAC). Here, we showed that the left ventricle (LV) of human failing heart was depleted in total glutathione by 54%. Similarly, 2-month post-myocardial infarction (MI) rats, with established chronic heart failure (CHF), displayed deficiency in LV glutathione. One-month oral NAC treatment normalized LV glutathione, improved LV contractile function and lessened adverse LV remodelling in 3-month post-MI rats. Biochemical studies at two time-points of NAC treatment, 3 days and 1 month, showed that inhibition of the neutral sphingomyelinase (N-SMase), Bcl-2 depletion and caspase-3 activation, were key, early and lasting events associated with glutathione repletion. Attenuation of oxidative stress, downregulation of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and its TNF-R1 receptor were significant after 1-month NAC treatment. These data indicate that, besides glutathione deficiency, N-SMase activation is associated with post-MI CHF progression, and that blockade of N-SMase activation participates to post-infarction failing heart recovery achieved by NAC treatment. NAC treatment in post-MI rats is a way to disrupt the vicious sTNF-alpha/TNF-R1/N-SMase cycle.
Published: 2007

37. Neutral sphingomyelinase inhibition participates to the benefits of N-acetylcysteine treatment in post-myocardial infarction failing heart rats

Author: Adamy, Christophe, Mulder, Paul, Khouzami, Lara, Andrieu-Abadie, Nathalie, Defer, Nicole, Candiani, Gabriele, Pavoine, Catherine, Caramelle, Philippe, Souktani, Richard, Le Corvoisier, Philippe, Perier, Magali, Kirsch, Matthias, Damy, Thibaud, Berdeaux, Alain, Levade, Thierry, Thuillez, Christian, Hittinger, Luc, Pecker, Françoise, 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), Institut Mondor de médecine moléculaire (Im3), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Pharmacologie des Dysfonctionnements Endotheliaux et Myocardiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - CHU Henri Mondor, Fédération de cardiologie, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, neutral sphingomyelinase, tumor necrosis factor-alpha, glutathione, N-acetylcysteine, chronic heart failure
Abstract: Deficiency in cellular thiol tripeptide glutathione (l-gamma glutamyl-cysteinyl-glycine) determines the severity of several chronic and inflammatory human diseases that may be relieved by oral treatment with the glutathione precursor N-acetylcysteine (NAC). Here, we showed that the left ventricle (LV) of human failing heart was depleted in total glutathione by 54%. Similarly, 2-month post-myocardial infarction (MI) rats, with established chronic heart failure (CHF), displayed deficiency in LV glutathione. One-month oral NAC treatment normalized LV glutathione, improved LV contractile function and lessened adverse LV remodelling in 3-month post-MI rats. Biochemical studies at two time-points of NAC treatment, 3 days and 1 month, showed that inhibition of the neutral sphingomyelinase (N-SMase), Bcl-2 depletion and caspase-3 activation, were key, early and lasting events associated with glutathione repletion. Attenuation of oxidative stress, downregulation of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and its TNF-R1 receptor were significant after 1-month NAC treatment. These data indicate that, besides glutathione deficiency, N-SMase activation is associated with post-MI CHF progression, and that blockade of N-SMase activation participates to post-infarction failing heart recovery achieved by NAC treatment. NAC treatment in post-MI rats is a way to disrupt the vicious sTNF-alpha/TNF-R1/N-SMase cycle.
Published: 2007

38. Neutral sphingomyelinase inhibition participates to the benefits of N-acetylcysteine treatment in post-myocardial infarction failing heart rats.: NAC treatment in post-MI failing heart rat

Author: Catherine Pavoine, Philippe Le Corvoisier, C. Adamy, Françoise Pecker, Nicole Defer, Richard Souktani, Alain Berdeaux, Paul Mulder, Magali Perier, Philippe Caramelle, Christian Thuillez, Lara Khouzami, Gabriele Candiani, M. Kirsch, Thibaud Damy, Nathalie Andrieu-Abadie, Luc Hittinger, Thierry Levade, 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), Institut Mondor de médecine moléculaire (Im3), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Pharmacologie des Dysfonctionnements Endotheliaux et Myocardiques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - CHU Henri Mondor, Fédération de cardiologie, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: Male, medicine.medical_specialty, Cardiotonic Agents, Time Factors, medicine.medical_treatment, Myocardial Infarction, Infarction, medicine.disease_cause, Acetylcysteine, chemistry.chemical_compound, Downregulation and upregulation, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, neutral sphingomyelinase, Internal medicine, Medicine, Animals, RNA, Messenger, Rats, Wistar, Molecular Biology, Heart Failure, business.industry, Tumor Necrosis Factor-alpha, Glutathione, tumor necrosis factor-alpha, medicine.disease, N-acetylcysteine, Echocardiography, Doppler, chronic heart failure, Rats, Disease Models, Animal, Oxidative Stress, Cytokine, Endocrinology, Sphingomyelin Phosphodiesterase, chemistry, Receptors, Tumor Necrosis Factor, Type I, Heart failure, Case-Control Studies, Tumor necrosis factor alpha, Cardiology and Cardiovascular Medicine, business, Oxidative stress, medicine.drug
Abstract: Deficiency in cellular thiol tripeptide glutathione (l-gamma glutamyl-cysteinyl-glycine) determines the severity of several chronic and inflammatory human diseases that may be relieved by oral treatment with the glutathione precursor N-acetylcysteine (NAC). Here, we showed that the left ventricle (LV) of human failing heart was depleted in total glutathione by 54%. Similarly, 2-month post-myocardial infarction (MI) rats, with established chronic heart failure (CHF), displayed deficiency in LV glutathione. One-month oral NAC treatment normalized LV glutathione, improved LV contractile function and lessened adverse LV remodelling in 3-month post-MI rats. Biochemical studies at two time-points of NAC treatment, 3 days and 1 month, showed that inhibition of the neutral sphingomyelinase (N-SMase), Bcl-2 depletion and caspase-3 activation, were key, early and lasting events associated with glutathione repletion. Attenuation of oxidative stress, downregulation of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and its TNF-R1 receptor were significant after 1-month NAC treatment. These data indicate that, besides glutathione deficiency, N-SMase activation is associated with post-MI CHF progression, and that blockade of N-SMase activation participates to post-infarction failing heart recovery achieved by NAC treatment. NAC treatment in post-MI rats is a way to disrupt the vicious sTNF-alpha/TNF-R1/N-SMase cycle.
Published: 2007

39. At-Risk Phenotype of Neurofibromatose-1 Patients: A Multicentre Case-Control Study

Author: Sébastien Barbarot, Patrick Combemale, Alain Drouet, Laurence Valeyrie-Allanore, Pierre Brugière, Salah Ferkal, Emilie Sbidian, Pierre Wolkenstein, Sylvie Bastuji-Garin, Cédric Vialette, Jean Pascal Lefaucheur, Laboratoire d'Investigation Clinique (LIC), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Pôle Recherche Clinique-Santé Publique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Service de dermatologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de référence des Neurofibromatoses, 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), Service de physiologie, explorations fonctionnelles [Mondor], Excitabilité nerveuse et thérapeutique (ENT), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-EA 4391, Service de Physiologie Explorations Fonctionnelles-Hôpital Henri Mondor, Service de Neurologie, Hôpital d'Instruction des armées, Service de Dermatologie, Centre Léon Bérard [Lyon], Service de Neuroradiologie, Unité de recherche clinique, Réseau NF-Rhône-Alpin, CHU Hotel Dieu, Grant from the Programme Hospitalier de Recherche Clinique (PHRC, AOM05116/P051014), Ministry of Health., Hôpital Henri Mondor-EA 4391, Service de Physiologie Explorations Fonctionnelles-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and BMC, Ed.
Subjects: Adult, Male, medicine.medical_specialty, Neurofibromatosis 1, Skin Neoplasms, Nerve root, lcsh:Medicine, [SDV.GEN] Life Sciences [q-bio]/Genetics, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Subcutaneous Tissue, Internal medicine, medicine, Neurofibroma, Humans, Genetics(clinical), Pharmacology (medical), Prospective Studies, Neurofibromatosis, Prospective cohort study, Genetics (clinical), 030304 developmental biology, Medicine(all), 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Research, lcsh:R, Case-control study, Peripheral Nervous System Diseases, General Medicine, Middle Aged, medicine.disease, Spinal cord, Magnetic Resonance Imaging, Radiography, medicine.anatomical_structure, Peripheral neuropathy, Phenotype, Case-Control Studies, Female, Sciatic nerve, business, 030217 neurology & neurosurgery
Abstract: Objectives To assess associations between subcutaneous neurofibromas (SC-NFs) and internal neurofibromas in patients with neurofibromatosis type 1 (NF-1) and to determine whether the association between SC-NFs and peripheral neuropathy was ascribable to internal neurofibromas. Patients and methods Prospective multicentre case-control study. Between 2005 and 2008, 110 NF-1 adults having two or more SC-NFs were individually matched for age, sex and hospital with 110 controls who had no SC-NF. Patients underwent standardized MRI of the spinal cord, nerve roots and sciatic nerves and an electrophysiological study. Analyses used adjusted multinomial logistic regression (ORa) to estimate the risk of the presence of internal neurofibromas or peripheral neuropathies associated with patients presented 2 to 9 SC-NFs, at least 10 SC-NFs as compared to patients without any (referential category). Results Cases had a mean age of 41 (± 13) years; 85 (80%) had two to nine SC-NFs and 21 (19%) at least ten SC-NFs. SC-NFs were more strongly associated with internal neurofibromas in patients with ten or more SC-NFs than in patients with fewer NF-SCs (e.g., sciatic nerve, aOR = 29.1 [8.5 to 100] vs. 4.3 [2.1 to 9.0]). The association with SC-NFs was stronger for diffuse, intradural, and > 3 cm internal neurofibromas than with other internal neurofibromas. Axonal neuropathy with slowed conduction velocities (SCV) was more strongly associated with having at least ten SC-NFs (aOR = 29.9, 5.5 to 162.3) than with having fewer SC-NFs (aOR = 4.4, 0.9 to 22.0). Bivariate analyses showed that the association between axonal neuropathy with SCV and sciatic neurofibromas was mediated by the association between SC-NFs and sciatic neurofibromas. Conclusion The at-risk phenotype of NF-1 patients (i.e. NF-1 patients with SC-NFs) is ascribable to associations linking SC-NFs to internal neurofibromas at risk for malignant transformation and to axonal neuropathies with slowed conduction velocities. Axonal neuropathies with SCV are particularly common in patients with at least ten SC-NFs. Registration details ORPHA86301
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Journal

Database

Publisher

39 results on '"CIC - CHU Henri Mondor"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources