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72 results on '"Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)"'

1. Alpha-phase synchrony EEG training for multi-resistant chronic low back pain patients: an open-label pilot study

Author: Marco Congedo, Arnaud Dupeyron, M. Ritz, Hélène Wu, Quentin Barthélemy, Patrick Favennec, Y. Delpierre, Louis Mayaud, Mensia Technologies [Paris], Covea Tech [Paris], Centre de l'Arche [PRH Le Mans], GIPSA - Vision and Brain Signal Processing (GIPSA-VIBS), Département Images et Signal (GIPSA-DIS), Grenoble Images Parole Signal Automatique (GIPSA-lab ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Grenoble Images Parole Signal Automatique (GIPSA-lab ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Département de Rééducation et Réadaptation Neuro Orthopédique [Nîmes] (Pôle NACRRE), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), and Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)
Subjects: Adult, medicine.medical_specialty, Adolescent, Visual Analog Scale, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Visual analogue scale, medicine.medical_treatment, Population, Pilot Projects, Context (language use), Electroencephalography, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, medicine, Humans, Orthopedics and Sports Medicine, education, ComputingMilieux_MISCELLANEOUS, 030222 orthopedics, education.field_of_study, Rehabilitation, Resting state fMRI, medicine.diagnostic_test, business.industry, Middle Aged, Neurofeedback, 3. Good health, Opioid, Conditioning, Operant, Female, Surgery, Chronic Pain, business, Low Back Pain, 030217 neurology & neurosurgery, medicine.drug
Abstract: Chronic low back pain (cLBP) affects a quarter of a population during its lifetime. The most severe cases include patients not responding to interventions such as 5-week-long in-hospital multi-disciplinary protocols. This document reports on a pilot study offering an alpha-phase synchronization (APS) brain rehabilitation intervention to a population of n = 16 multi-resistant cLBP patients. The intervention consists of 20 sessions of highly controlled electroencephalography (EEG) APS operant conditioning (neurofeedback) paradigm delivered in the form of visual feedback. Visual analogue scale for pain, Dallas, Hamilton, and HAD were measured before, after, at 6-month and 12-month follow-up. Full-scalp EEG data were analyzed to study significant changes in the brain’s electrical activity. The intervention showed a great and lasting response of most measured clinical scales. The clinical improvement was lasting beyond the 6-month follow-up endpoints. The EEG data confirm that patients did control (intra-session trends) and learned to better control (intersession trends) their APS neuromarker resulting in (nonsignificant) baseline changes in their resting state activity. Last and most significantly, the alpha-phase concentration (APC) neuromarker, specific to phase rather than amplitude, was found to correlate significantly with the reduction in clinical symptoms in a typical dose–response effect. This first experiment highlights the role of the APC neuromarker in relation to the nucleus accumbens activity and its role on nociception and the chronicity of pain. This study suggests APC rehabilitation could be used clinically for the most severe cases of cLBP. Its excellent safety profile and availability as a home-use intervention makes it a potentially disruptive tool in the context of nonsteroidal anti-inflammatory drugs and opioid abuses. These slides can be retrieved under Electronic Supplementary Material.
Published: 2019

2. Pathologic and MRI analysis in acute atypical inflammatory demyelinating lesions

Author: Thierry Vincent, A.-M. Guennoc, Pierre Labauge, Anne Kerbrat, François Cotton, Stéphane Kremer, Béatrice Carsin-Nicol, Mahmoud Charif, Sandra Vukusic, Thibaut Allou, Jérôme De Seze, Aurélie Ruet, Laurent Magy, Nicolas Menjot de Champfleur, Clarisse Carra-Dalliere, Guido Ahle, Eric Thouvenot, Françoise Durand-Dubief, Hélène Oesterle, Valérie Rigau, Denis Sablot, Romain Marignier, Nicolas Collongues, Gilles Edan, Mikael Cohen, Sonia Hebbadj, Benoit Lhermitte, Frederic Taithe, M. P. Boncoeur-Martel, Xavier Ayrignac, Grelier, Elisabeth, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service d'Anatomie Pathologique Générale, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Département d’Immunologie, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Service de radiologie [Strasbourg], Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Hôpitaux Civils de Colmar, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), 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), Pierre Wertheimer, Département de Neurologie, Service de Neurologie [Lyon], CHU Lyon, Service de Neurologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Pasteur [Nice] (CHU), Service de Neurologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Service de neurologie [Rennes], Université de Rennes (UR), Service de neurochirurgie [Rennes] = Neurosurgery [Rennes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de Neurologie [CHU Nimes] (Pôle NIRR), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Neuroinflammation: imagerie et thérapie de la sclérose en plaques, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHU Limoges], CHU Limoges, Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Service de Radiologie et Imagerie Médicale [CHU Limoges], Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-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), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), 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: Adult, Male, Atypical inflammatory demyelinating syndrome, medicine.medical_specialty, Pathology, Multiple Sclerosis, Histopathology, Context (language use), Immunopathology, Cohort Studies, Lesion, Young Adult, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, 030212 general & internal medicine, Pathological, Aged, Retrospective Studies, Neuroradiology, Aquaporin 4, medicine.diagnostic_test, business.industry, Multiple sclerosis, Brain biopsy, Neuromyelitis Optica, food and beverages, Magnetic resonance imaging, Middle Aged, medicine.disease, Atypical demyelinating lesions, Magnetic Resonance Imaging, 3. Good health, Neurology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Acute Disease, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Neurology (clinical), medicine.symptom, business, Aquaporin-4, 030217 neurology & neurosurgery, Demyelinating Diseases
Abstract: The diagnosis of atypical inflammatory demyelinating lesions can be difficult. Brain biopsy is often required to exclude neoplasms. Moreover, the relationship between these lesions and multiple sclerosis and NMOSD is not clear. Our objectives were to describe radiological and pathological characteristics of patients with acute inflammatory demyelinating lesions. We retrospectively identified patients with brain biopsy performed for diagnostic uncertainty revealing a demyelinating lesion. A complete clinical, biological, radiological and pathological analysis was performed. Twenty patients (15 with a single lesion) were included. MRI disclosed a wide range of lesions including infiltrative lesions (40%), ring-like lesion (15%) Balo-like lesion (15%) and acute haemorrhagic leukoencephalitis (20%). In spite of a marked heterogeneity, some findings were common: a peripheral B1000 hyperintense rim (70%), a slight oedema with mild mass effect (75%) and an open-rim peripheral enhancement (75%). Histopathology revealed that all cases featured macrophages distributed throughout, extensive demyelination, axonal preservation and absence of haemorrhagic changes. In the majority of cases, macrophages were the predominant inflammatory infiltrate and astrocytes were reactive and dystrophic. Aquaporin-4 staining was systematically preserved. After a mean follow-up of 5 years (1–12), 16/20 patients had a diagnosis of monophasic acute atypical inflammatory demyelinating lesion. One patient was diagnosed with MS and 3 with AQP4 negative NMOSD. Although imaging findings in patients with atypical inflammatory demyelinating lesions are heterogeneous, some common features such as peripheral DWI hyperintense rim with open-rim enhancement and absence of oedema argue in favour of a demyelinating lesion and should preclude a brain biopsy. In this context, AQP4 staining is systematically preserved and argues against an AQP4-positive NMOSD. Moreover, long-term follow-up is characterized by low recurrence rate.
Published: 2019

3. Usefulness of MOG-antibody titres at first episode to predict the future clinical course in adults

Author: Nuria Sola-Valls, Sandra Vukusic, Françoise Durand-Dubief, Eric Thouvenot, Damien Biotti, Hélène Zéphir, Sara Llufriu, Caroline Papeix, Elisabeth Maillart, Romain Deschamps, Nicolas Collongues, Albert Saiz, Pierre Labauge, Alexis Montcuquet, Anne Ruiz, Thaís Armangue, Alvaro Cobo-Calvo, Maria S. Sepúlveda, Xavier Ayrignac, Bertrand Audoin, Jérôme De Seze, Hyacintha d'Indy, Yolanda Blanco, Romain Marignier, Jonathan Ciron, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), 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), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Sant Joan de Déu-Barcelona Children's Hospital's, Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Neurologie, maladies neuro-musculaires [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Neurologie [Hôpital Roger Salengro], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département de Neurologie [Toulouse], Institut des Neurosciences [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre référent Sclérose Latérale Amyotrophique [CHRU Montpellier] (SLA CHRU Montpellier), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Neurologie [CHU Nimes] (Pôle NIRR), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de Neurologie [CHU Limoges], CHU Limoges, Fondation Ophtalmologique Adolphe de Rotschild, Clinical and experimental neuroimmunology [IDIBAPS], Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospices Civils de Lyon, Departement de Neurologie (HCL), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-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), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)
Subjects: Male, Visual acuity, Optic neuritis, Logistic regression, Gastroenterology, 0302 clinical medicine, Recurrence, immune system diseases, Medicine, 030212 general & internal medicine, 10. No inequality, First episode, hemic and immune systems, Middle Aged, Myelitis, Prognosis, Neuromyelitis optica, 3. Good health, Titer, MESH: Autoantibodies / blood, Demyelinating diseases / immunology, HEK293 Cells, Young Adults, Neurology, Titre, Cohort, Disease Progression, [SDV.IMM]Life Sciences [q-bio]/Immunology, Biological Assay, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Adult, medicine.medical_specialty, Adolescent, MOG antibodies, Young Adult, 03 medical and health sciences, Internal medicine, Humans, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Autoantibodies, Retrospective Studies, business.industry, Proportional hazards model, Retrospective cohort study, medicine.disease, nervous system diseases, nervous system, Myelin-Oligodendrocyte Glycoprotein, Neurology (clinical), business, 030217 neurology & neurosurgery, Demyelinating Diseases, Follow-Up Studies
Abstract: OBJECTIVE: To analyze whether myelin oligodendrocyte glycoprotein antibody (MOG-Ab) titres at onset of the disease were different according to the clinical phenotype at presentation, and to investigate whether the titres were associated with risk of further relapses or predicted clinical outcome in adult patients. Finally, we assessed an alternative method to the classical measurement of MOG-Ab levels by serial dilutions. METHODS: This is a retrospective study including 79 MOG-Ab-positive adult patients, whose samples were obtained at first episode. MOG-Ab were tested by cell-based assay. HEK293 cells were transfected (tHEK293) with human-MOG plasmid. Non-tHEK293 cells were used as negative controls. Assessment of antibody titres was performed by serial dilution, and delta mean fluorescence intensity ratio signal (MOG-ratio MFI) by flow cytometry. MOG-ratio MFI was calculated as follows: (MFI tHEK293cells- MFI non-tHEK293cells)/MFI non-tHEK293cells. MOG-ratio MFI was calculated from the first serum dilution at 1:320. The association between MOG-Ab titres and risk of relapse was analyzed by Cox regression. The association between MOG-Ab titres and visual or motor disability at last follow-up was performed by binary logistic regression. Poor visual outcome was defined when patients displayed some degree of visual disability (visual acuity [VA] < 20/20) and poor motor outcome when patients displayed some degree of motor disability (Disability Status Scale [DSS] > 1). We also investigated correlations between MOG-Ab titres and MOG-ratio MFI. RESULTS: MOG-Ab titres were higher in Caucasians than in those with other ethnicities, and in patients with a more severe VA (VA = 20/100) or motor disability (DSS = 3.0) at onset (p = 0.006, 0.034, and 0.058, respectively). MOG-Ab titres were not associated with risk of relapses or with the final clinical outcome. MOG-ratio MFI correlated with MOG-Ab titres in the whole cohort (? = 0.90; p < 0.001), and when stratified by initial clinical phenotype. CONCLUSION: High MOG-Ab titres at onset are associated with a more severe presentation, but do not predict the future disease course. MOG-ratio MFI is an alternative and straightforward method to determine MOG-Ab levels.
Published: 2019

4. Feasibility of remote digital monitoring using wireless Bluetooth monitors, the Smart Angel™ app and an original web platform for patients following outpatient surgery: a prospective observational pilot study

Author: Noemie Chaniaud, Ariane Lannelongue, Bob-Valéry Occéan, Jean-Yves Lefrant, Christophe Boisson, Philippe Cuvillon, Gautier Buzancais, natacha simon, Pierre Rataboul, T. Chevallier, Yann Gricourt, Laboratoire de Biostatistique, Epidémiologie clinique, Santé Publique Innovation et Méthodologie [CHU Nîmes] (BESPIM), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre de Recherche en Psychologie : Cognition, Psychisme et Organisations - UR UPJV 7273 (CRP-CPO), and Université de Picardie Jules Verne (UPJV)
Subjects: Adult, Male, Usability, Outpatient surgery, Pilot Projects, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, law.invention, lcsh:RD78.3-87.3, Bluetooth, 03 medical and health sciences, 0302 clinical medicine, Software, 030202 anesthesiology, law, medicine, Humans, Device, Wireless, Prospective Studies, Monitoring, Physiologic, business.industry, System usability scale, Hemodynamics, Ambulatory surgery, 030208 emergency & critical care medicine, Middle Aged, medicine.disease, 3. Good health, Remote monitoring, Anesthesiology and Pain Medicine, Ambulatory Surgical Procedures, lcsh:Anesthesiology, Remote Sensing Technology, Ambulatory, Feasibility Studies, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Observational study, Medical emergency, business, Wireless Technology, Research Article
Abstract: Background Remote monitoring of mean arterial blood pressure (MAP), heart rate (HR) or oxygen saturation (SpO2) remains a challenge in outpatient surgery. This study evaluates a new digital technology (Smart Angel™) for remotely monitoring hemodynamic data in real time: data transmitted from the patient’s home to a central server, using a dedicated web-based software package. Methods Adults scheduled for elective outpatient surgery were prospectively enrolled. In the first 5 postoperative days, patients completed a self-report questionnaire (pain, comfort, nausea, vomiting) and recorded SpO2, HR and MAP via two wireless Bluetooth monitors connected to a 4G tablet to transmit the data to a website, in real time, using Smart Angel™ software. Before transmission to the website, these data were also self-reported by the patient on a paper form. The primary outcome was the proportion of variables (self-monitored physiological data + questionnaire scores) correctly transmitted to the hospital via the system compared with the paper version. On Day 5, a system usability scale survey (SUS score 1–100) was also attributed. Results From May 2018 to September 2018, data were available for 29 out of 30 patients enrolled (1 patient was not discharged from hospital after surgery). The remote monitoring technology recorded 2038 data items (62%) compared with 2656 (82%) items recorded on the paper form (p = 0.001). The most common errors with the remote technology were software malfunctioning when starting the MAP monitor and malfunctioning between the tablet and the Bluetooth monitor. No serious adverse events were noted. The SUS score for the system was 85 (68–93) for 26 patients. Conclusion This work evaluates the ability of a pilot system for monitoring remote physiological data using digital technology after ambulatory surgery and highlights the digital limitations of this technology. Technological improvements are required to reduce malfunctioning (4G access, transmission between apps). Trial registration ClinicalTrials.gov (NCT03464721) (March 8, 2018).
Published: 2020

5. Interaction of Cutibacterium ( formerly Propionibacterium) acnes with bone cells: a step toward understanding bone and joint infection development

Author: Dominique Heymann, Guillaume Ghislain Aubin, Didier Lepelletier, Cédric Jacqueline, Jean-Philippe Lavigne, Régis Brion, Marc Baud'huin, Stéphane Corvec, Karim Asehnoune, François Gouin, Service de bactériologie et hygiène hospitalière [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Thérapeutiques cliniques et expérimentales des infections (EA 3826) (EA 3826), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre hospitalier universitaire de Nantes (CHU Nantes), Virulence bactérienne et maladies infectieuses (VBMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Département de Microbiologie [Nîmes], Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Clinique chirurgicale orthopédique et traumatique [Nantes], Department of Oncology and Metabolism [Sheffield, UK], The University of Sheffield [Sheffield, U.K.], Clinical and Translational Research in Skin Cancer (CRCINA-ÉQUIPE 2), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université de Nantes ( UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Thérapeutiques Cliniques et Expérimentales des Infections, Université de Nantes ( UN ), Physiopathologie de la Résorption Osseuse et Thérapie des Tumeurs Osseuses Primitives, Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Virulence bactérienne et maladies infectieuses, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), European Associated Laboratory [Sheffield, UK] ( Sarcoma Research Unit ), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers ( CRCINA ), Université d'Angers ( UA ) -Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche en Santé de l'Université de Nantes ( IRS-UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), maurice, sandrine, Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: 0301 basic medicine, Cell Survival, 030106 microbiology, [ SDV.MHEP.PED ] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Genome, Article, Monocytes, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Microbiology, [ SDV.MHEP.RSOA ] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, 03 medical and health sciences, Propionibacterium acnes, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Cell Line, Tumor, Bone cell, Humans, Gene, Pathogen, Gram-Positive Bacterial Infections, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Multidisciplinary, Whole Genome Sequencing, biology, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, biology.organism_classification, Phenotype, 3. Good health, Resorption, 030104 developmental biology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Multilocus sequence typing, Bone Diseases, Joint Diseases, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Multilocus Sequence Typing
Abstract: Cutibacterium acnes (formerly Propionibacterium acnes) is recognized as a pathogen in foreign-body infections (arthroplasty or spinal instrumentation). To date, the direct impact of C. acnes on bone cells has never been explored. The clade of 11 C. acnes clinical isolates was determined by MLST. Human osteoblasts and osteoclasts were infected by live C. acnes. The whole genome sequence of six isolates of this collection was analyzed. CC36 C. acnes strains were significantly less internalized by osteoblasts and osteoclasts than CC18 and CC28 C. acnes strains (p ≤ 0.05). The CC18 C. acnes ATCC6919 isolate could survive intracellularly for at least 96 hours. C. acnes significantly decreased the resorption ability of osteoclasts with a major impact by the CC36 strain (p ≤ 0.05). Genome analysis revealed 27 genes possibly linked to these phenotypic behaviors. We showed a direct impact of C. acnes on bone cells, providing new explanations about the development of C. acnes foreign-body infections.
Published: 2017

6. Integrated chronic disease management to avoid emergency departments: the MACVIA-LR® approach

Author: Olivier Jonquet, Pierre-Géraud Claret, Jean-Emmanuel de La Coussaye, Xavier Bobbia, Jean Bousquet, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Université Montpellier 1 (UM1), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: medicine.medical_specialty, business.industry, General Practice, MEDLINE, Disease Management, medicine.disease, 3. Good health, Chronic disease, Chronic Disease, Emergency Medicine, Internal Medicine, medicine, Humans, France, Medical emergency, Disease management (health), Emergency Service, Hospital, Intensive care medicine, business, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2014

7. Health-related quality of life analysis in ovarian cancer clinical trials involving PARP inhibitors: a critical methodological perspective

Author: Frédéric, Fiteni, Julien, Peron, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université de Montpellier (UM), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), and Université de Lyon
Subjects: Ovarian Neoplasms, MESH: Humans, MESH: Adenosine Diphosphate, Ribose, Health-related quality of life, Public Health, Environmental and Occupational Health, MESH: Quality of Life, Poly(ADP-ribose) Polymerase Inhibitors, Adenosine Diphosphate, MESH: Poly(ADP-ribose) Polymerase Inhibitors, MESH: Ribose, MESH: Ovarian Neoplasms, PARP inhibitor, Ovarian cancer, Statistical analysis, Quality of Life, Humans, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Female
Abstract: International audience; The poly (ADP-ribose) polymerase inhibitors (PARPi) have yielded significant clinical benefits as maintenance therapy in women with newly diagnosed and relapsed platinum-sensitive advanced ovarian cancer. These drugs were approved based on progression-free survival, the primary endpoint of their respective pivotal trials. Health-related quality of life (HRQoL) and/or patient-reported outcomes were included in these trials as a secondary exploratory endpoint. Nevertheless, many weaknesses in the analysis of HRQoL across these trials can be noticed. Heterogeneity and suboptimal HRQoL analysis in oncology trials contribute to misconceptions about this endpoint among oncologists and prevent quality of life as being an endpoint used for approvals. In this article, we discuss these HRQoL results from a methodological perspective and propose some solutions for improvement that could be used by regulatory and academic institutions running ovarian cancers trials. Notably, we suggest to measure and analyze HRQoL data after disease progression, to focus dedicated papers on the statistical analyses of HRQoL recommended by the SISAQOL consortium (linear mixed model for repeated measures and time-to-event approaches) and to communicate on available guidelines to ensure compliance with best international practices regarding the measurement and analysis of HRQoL.
Published: 2022

8. Serum procalcitonin and C-reactive protein concentrations to distinguish mildly infected from non-infected diabetic foot ulcers: a pilot study

Author: Pierre Corbeau, Jean-Philippe Lavigne, Nathalie Jourdan, Christophe Combescure, M. Rodier, A. Jeandrot, Albert Sotto, J.-L. Richard, S. Finge, Laboratoire de bactériologie, virologie et parasitologie, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service des maladies de la nutrition et de diabétologie, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Département de l'information médicale, Service des maladies métaboliques et endocriniennes, Service d'immunologie, Systèmes de sécrétion de type IV et virulence bactérienne, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Lavigne, Jean-Philippe
Subjects: medicine.medical_specialty, Pathology, biology, business.industry, Endocrinology, Diabetes and Metabolism, C-reactive protein, Virulence, medicine.disease, Gastroenterology, Diabetic foot, Article, digestive system diseases, Procalcitonin, Diabetic foot ulcer, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Predictive value of tests, Internal medicine, Diabetes mellitus, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal Medicine, Normal flora, medicine, biology.protein, business
Abstract: International audience; AIMS/HYPOTHESIS: Infection of diabetic foot ulcers is common; at early stages it is difficult to differentiate between non-infected ulcers (or those colonised with normal flora) and ulcers infected with virulent bacteria that lead to deterioration. This pilot study aimed to assess the diagnostic accuracy of inflammatory markers as an aid to making this distinction. METHODS: We included 93 diabetic patients who had an episode of foot ulcer and had not received antibiotics during the 6 months preceding the study. Ulcers were classified as infected or uninfected, according to the Infectious Diseases Society of America-International Working Group on the Diabetic Foot classification. Diabetic patients without ulcers (n = 102) served as controls. C-reactive protein (CRP), orosomucoid, haptoglobin and procalcitonin were measured together with white blood cell and neutrophil counts. The diagnostic performance of each marker, in combination (using logistic regression) or alone, was assessed. RESULTS: As a single marker, CRP was the most informative for differentiating grade 1 from grade 2 ulcers (sensitivity 0.727, specificity 1.000, positive predictive value 1.000, negative predictive value 0.793) with an optimal cut-off value of 17 mg/l. In contrast, white blood cell and neutrophil counts were not predictive. The most relevant combination derived from the logistic regression was the association of CRP and procalcitonin (AUC 0.947), which resulted in a significantly more effective determination of ulcer grades, as shown by comparing receiver operating characteristic curves. CONCLUSIONS/INTERPRETATION: Measurement of only two inflammatory markers, CRP and procalcitonin, might be of value for distinguishing between infected and non-infected foot ulcers in subgroups of diabetic patients, to help ensure the appropriate allocation of antibiotic treatment. Nevertheless, external validation of the diagnostic value of procalcitonin and CRP in diabetic foot ulcers is needed before routine use can be recommended.
Published: 2007

9. Comparison of 8 versus 15 days of antibiotic therapy for Pseudomonas aeruginosa ventilator-associated pneumonia in adults: a randomized, controlled, open-label trial

Author: Adrien, Bouglé, Sophie, Tuffet, Laura, Federici, Marc, Leone, Antoine, Monsel, Thomas, Dessalle, Julien, Amour, Claire, Dahyot-Fizelier, François, Barbier, Charles-Edouard, Luyt, Olivier, Langeron, Bernard, Cholley, Julien, Pottecher, Tarik, Hissem, Jean-Yves, Lefrant, Benoit, Veber, Matthieu, Legrand, Alexandre, Demoule, Pierre, Kalfon, Jean-Michel, Constantin, Alexandra, Rousseau, Tabassome, Simon, Arnaud, Foucrier, Nora, Soussi, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Sud Francilien, Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre d'investigation clinique Biothérapie [CHU Pitié-Salpêtrière] (CIC-BTi), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pharmacologie des anti-infectieux et antibiorésistance (PHAR2), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Régional d'Orléans (CHRO), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), CHU Strasbourg, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Initial MAnagement and prevention of acute orGan failures IN critically ill patiEnts (IMAGINE), Université de Montpellier (UM), CHU Rouen, Normandie Université (NU), Hôpital Lariboisière-Fernand-Widal [APHP], Hôpital Louis Pasteur [Chartres], CHU Clermont-Ferrand, Centre de Ressources Biologiques APHP-SU (PASS-CRB-APHP-SU), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Hôpital Beaujon [AP-HP]
Subjects: Adult, MESH: Humans, Survival, Pneumonia, Ventilator-Associated, MESH: Adult, MESH: Pneumonia, Ventilator-Associated, Antibiotic therapy, Critical Care and Intensive Care Medicine, Respiration, Artificial, Anti-Bacterial Agents, Ventilator-associated pneumonia, Intensive Care Units, Recurrence, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Anti-Bacterial Agents, MESH: Intensive Cate Units, MESH: Pseudomonas aeruginosa, Pseudomonas aeruginosa, Humans, MESH: Respiration, Artificial
Abstract: International audience; Purpose: Duration of antibiotic therapy for ventilator-associated pneumonia (VAP) due to non-fermenting Gram-negative bacilli (NF-GNB), including Pseudomonas aeruginosa (PA) remains uncertain. We aimed to assess the non-inferiority of a short duration of antibiotics (8 days) vs. prolonged antibiotic therapy (15 days) in VAP due to PA (PA-VAP).Methods: We conducted a nationwide, randomized, open-labeled, multicenter, non-inferiority trial to evaluate optimal duration of antibiotic treatment in PA-VAP. Eligible patients were adults with diagnosis of PA-VAP and randomly assigned in 1:1 ratio to receive a short-duration treatment (8 days) or a long-duration treatment (15 days). A pre-specified analysis was used to assess a composite endpoint combining mortality and PA-VAP recurrence rate during hospitalization in the intensive care unit (ICU) within 90 days.Results: The study was stopped after 24 months due to slow inclusion rate. In intention-to-treat population (n = 186), the percentage of patients who reached the composite endpoint was 25.5% (N = 25/98) in the 15-day group versus 35.2% (N = 31/88) in the 8-day group (difference 9.7%, 90% confidence interval (CI) -1.9%-21.2%). The percentage of recurrence of PA-VAP during the ICU stay was 9.2% in the 15-day group versus 17% in the 8-day group. The two groups had similar median days of mechanical ventilation, of ICU stay, number of extra pulmonary infections and acquisition of multidrug-resistant (MDR) pathogens during ICU stay.Conclusions: Our study failed to show the non-inferiority of a short duration of antibiotics in the treatment of PA-VAP, compared to a long duration. The short duration strategy may be associated to an increase of PA-VAP recurrence. However, the lack of power limits the interpretation of this study.
Published: 2022

10. Intensive chemotherapy followed by autologous stem cell transplantation in primary central nervous system lymphomas (PCNSLs). Therapeutic outcomes in real life—experience of the French Network

Author: Schenone, Laurence, Houillier, Caroline, Tanguy, Marie Laure, Choquet, Sylvain, Agbetiafa, Kossi, Ghesquières, Hervé, Damaj, Gandhi, Schmitt, Anna, Bouabdallah, Krimo, Ahle, Guido, Gressin, Remy, Cornillon, Jérôme, Houot, Roch, Marolleau, Jean-Pierre, Fornecker, Luc-Matthieu, Chinot, Olivier, Peyrade, Frédéric, Bouabdallah, Reda, Moluçon-Chabrot, Cécile, Gyan, Emmanuel, Chauchet, Adrien, Casasnovas, Olivier, Oberic, Lucie, Delwail, Vincent, Abraham, Julie, Roland, Virginie, Waultier-Rascalou, Agathe, Willems, Lise, Morschhauser, Franck, Fabbro, Michel, Ursu, Renata, Thieblemont, Catherine, Jardin, Fabrice, Tempescul, Adrian, Malaise, Denis, Touitou, Valérie, Nichelli, Lucia, Le Garff-Tavernier, Magali, Plessier, Aurélie, Bourget, Philippe, Bonmati, Caroline, Wantz-Mézières, Sophie, Giordan, Quentin, Dorvaux, Véronique, Charron, Cyril, Jabeur, Waliyde, Hoang-Xuan, Khê, Taillandier, Luc, Soussain, Carole, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département d'hématologie, Institut Curie, Site Saint-Cloud, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Bergonié [Bordeaux], UNICANCER, CHU Bordeaux [Bordeaux], Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Centre Hospitalier Universitaire [Grenoble] (CHU), Institut de Cancérologie Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), 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 ), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Strasbourg, Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Hôpital Dupuytren [CHU Limoges], Centre Hospitalier Saint Jean de Perpignan, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut du Cancer de Montpellier (ICM), Hopital Saint-Louis [AP-HP] (AP-HP), NF-kappaB, Différenciation et Cancer (OncokappaB (URP_7324)), Université Paris Cité (UPCité), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Département d'Oncologie Chirurgicale [Institut Curie], Institut Curie [Paris], Laboratoire d'Imagerie Translationnelle en Oncologie (LITO ), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Beaujon [AP-HP], CHU Necker - Enfants Malades [AP-HP], Biology, genetics and statistics (BIGS), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut Élie Cartan de Lorraine (IECL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut Élie Cartan de Lorraine (IECL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Hôpital de Mercy, Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Hôpital Ambroise Paré [AP-HP], Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de Recherche en Automatique de Nancy (CRAN), Institut Curie - Saint Cloud (ICSC), Immunité et cancer (U932), and We thank the clinicians involved in the French National 'Lymphome Oculo-Cérébral' LOC network, part of the network for rare cancers of the central nervous system, 'RENOCLIP-LOC Network', approved by the French National Institute of Cancer (INCa).
Subjects: Transplantation, Hematology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; We analysed the therapeutic outcomes of all consecutive patients with primary central nervous system lymphoma (PCNSL) registered in the prospective French database for PCNSL and treated with intensive chemotherapy (IC) followed by autologous stem cell transplantation (IC-ASCT) between 2011 and November 2019 (271 patients recruited, 266 analysed). In addition, treatment-related complications of thiotepa-based IC-ASCT were analysed from the source files of 85 patients from 3 centers. Patients had received IC-ASCT either in first-line treatment (n\,=\,147) or at relapse (n\,=\,119). The median age at IC-ASCT was 57 years (range: 22-74). IC consisted of thiotepa-BCNU (n\,=\,64), thiotepa-busulfan (n\,=\,24), BCNU-etoposide-cytarabine-melphalan (BEAM, n\,=\,36) and thiotepa-busulfan-cyclophosphamide (n\,=\,142). In multivariate analysis, BEAM and ASCT beyond the first relapse were adverse prognostic factors for relapse risk. The risk of treatment-related mortality was higher for ASCT performed beyond the first relapse and seemed higher for thiotepa-busulfan-cyclophosphamide. Thiotepa-BCNU tends to result in a higher relapse rate than thiotepa-busulfan-cyclophosphamide and thiotepa-busulfan. This study confirms the role of IC-ASCT in first-line treatment and at first-relapse PCNSL (5-year overall survival rates of 80 and 50%, respectively). The benefit/risk ratio of thiotepa-busulfan/thiotepa-busulfan-cyclophosphamide-ASCT could be improved by considering ASCT earlier in the course of the disease and dose adjustment of the IC.
Published: 2022

11. Cost-Effectiveness Evaluation of a Remote Monitoring Programme Including Lifestyle Education Software in Type 2 Diabetes: Results of the Educ@dom Study

Author: Michael, Mounié, Nadège, Costa, Pierre, Gourdy, Christelle, Latorre, Solène, Schirr-Bonnans, Jean-Marc, Lagarrigue, Henri, Roussel, Jacques, Martini, Jean-Christophe, Buisson, Marie-Christine, Chauchard, Jacqueline, Delaunay, Soumia, Taoui, Marie-France, Poncet, Valeria, Cosma, Sandrine, Lablanche, Magali, Coustols-Valat, Lucie, Chaillous, Charles, Thivolet, Caroline, Sanz, Alfred, Penfornis, Benoît, Lepage, Hélène, Colineaux, Hélène, Hanaire, Laurent, Molinier, Marie-Christine, Turnin, Université Fédérale Toulouse Midi-Pyrénées, Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP), 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), MSA Midi-Pyrénées Nord [Montauban] (MSA-MPN), Directions régionales du Service médical Occitanie [Toulouse] (DRSM / CNAM), DIAMIP Network [Toulouse] ( Association Diabète Occitanie), Ecole Nationale Supérieure d'Electrotechnique, d'Electronique, d'Informatique, d'Hydraulique et de Télécommunications (ENSEEIHT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Clinique Claude Bernard - ELSAN [Albi] (CCBE), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CHU Grenoble, Clinique Ambroise Paré - ELSAN [Toulouse] (CAPE), Centre hospitalier universitaire de Nantes (CHU Nantes), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de Lyon (CHU Lyon), Clinique Pasteur [Toulouse], Centre Hospitalier Sud Francilien, Educ@dom Study Group, and CarMeN, laboratoire
Subjects: [SDV] Life Sciences [q-bio], Telemonitoring, Educ@dom, Economic assessment, Tele-education, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Internal Medicine, Lifestyle management, Type 2 diabetes, Cost-effectiveness
Abstract: Erratum inCorrection to: Cost-Effectiveness Evaluation of a Remote Monitoring Programme Including Lifestyle Education Software in Type 2 Diabetes: Results of the Educ@dom Study.Mounié M, Costa N, Gourdy P, Latorre C, Schirr-Bonnans S, Lagarrigue JM, Roussel H, Martini J, Buisson JC, Chauchard MC, Delaunay J, Taoui S, Poncet MF, Cosma V, Lablanche S, Coustols-Valat M, Chaillous L, Thivolet C, Sanz C, Penfornis A, Lepage B, Colineaux H, Hanaire H, Molinier L, Turnin MC; Educ@dom Study Group, Benhamou PY, Rodier M, Ayon F, Puel-Olivier F, Fontaine S, Perron M, Arrivié J, Cousty-Pech F, Rouby C, Lafon F, Moura I.Diabetes Ther. 2022 May;13(5):1131-1132. doi: 10.1007/s13300-022-01248-6.PMID: 35316510 Free PMC article. No abstract available.; International audience; INTRODUCTION: Telemedicine programs using health technological innovation to remotely monitor the lifestyles of patients with type 2 diabetes (T2D) can improve glycaemic control and thus reduce the incidence of complications as well as management costs. In this context, an assessment was made of the 1-year and 2-year cost-effectiveness of the EDUC@DOM telemonitoring and tele-education program. METHODS: The EDUC@DOM study was a multicentre randomized controlled trial conducted between 2013 and 2017 that compared a telemonitoring group (TMG) to a control group (CG) merged with health insurance databases to extract economic data on resource consumption. Economic analysis was performed from the payer perspective, and direct costs and indirect costs were considered. The clinical outcome used was the intergroup change in glycated haemoglobin (HbA1c) levels from baseline. Missing economic data were imputed using multiple imputation, and fitted values from a generalized linear mixed model were used to calculate the incremental cost-effectiveness ratio (ICER). Bootstrapped 95% confidence ellipses were drawn in the cost-effectiveness plan. RESULTS: The main analysis included data from 256 patients: 126 in the TMG and 130 in the CG. Incremental costs over 1 and 2 years were equal to €2129 and €5101, respectively, in favour of the TMG. Once imputed and adjusted for confounding factors, the TMG trends to a 21% cost decrease over 1 and 2 years of follow-up (0.79 [0.58; 1.08], p = 0.1452 and 0.79 [0.61; 1.03], p = 0.0879, respectively). The EDUC@DOM program led to a €1334 cost saving and a 0.17 decrease in HbA1c over 1 year and a €3144 cost saving and a 0.14 decrease in HbA1c over 2 years. According to the confidence ellipse, EDUC@DOM was a cost-effective strategy. CONCLUSION: This study provides additional economic information on telemonitoring and tele-education programs to enhance their acceptance and promote their use. In the light of this work, the EDUC@DOM program is a cost-saving strategy in T2D management. TRIAL REGISTRATION: This trial was registered in the Clinical Trials Database on 27 September 2013 under no. NCT01955031 and bears ID-RCB no. 2013-A00391-44.
Published: 2022

12. T cell apoptosis characterizes severe Covid-19 disease

Author: Sonia André, Morgane Picard, Renaud Cezar, Florence Roux-Dalvai, Aurélie Alleaume-Butaux, Calaiselvy Soundaramourty, André Santa Cruz, Ana Mendes-Frias, Clarisse Gotti, Mickaël Leclercq, Alexandre Nicolas, Alexandra Tauzin, Alexandre Carvalho, Carlos Capela, Jorge Pedrosa, António Gil Castro, Lucy Kundura, Paul Loubet, Albert Sotto, Laurent Muller, Jean-Yves Lefrant, Claire Roger, Pierre-Géraud Claret, Sandra Duvnjak, Tu-Anh Tran, Gina Racine, Ouafa Zghidi-Abouzid, Pierre Nioche, Ricardo Silvestre, Arnaud Droit, Fabrizio Mammano, Pierre Corbeau, Jérôme Estaquier, Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre de recherche du CHU de Québec-Université Laval (CRCHUQ), CHU de Québec–Université Laval, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Biomedtech Facilities (UMS 2009 / US36), Universidade do Minho = University of Minho [Braga], ICVS/3B's - PT Government Associate Laboratory [Braga/Guimarães, Portugal] (AL), Hospital Escala Braga [Braga, Portugal], Institut de génétique humaine (IGH), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and Dupuis, Christine
Subjects: CD4-Positive T-Lymphocytes, Fas Ligand Protein, SARS-CoV-2, T-Lymphocytes, Immune cell death, [SDV]Life Sciences [q-bio], COVID-19, Apoptosis, Cell Biology, Microbiology, Article, [SDV] Life Sciences [q-bio], Caspases, Lymphopenia, Humans, fas Receptor, Molecular Biology
Abstract: Severe SARS-CoV-2 infections are characterized by lymphopenia, but the mechanisms involved are still elusive. Based on our knowledge of HIV pathophysiology, we hypothesized that SARS-CoV-2 infection-mediated lymphopenia could also be related to T cell apoptosis. By comparing intensive care unit (ICU) and non-ICU COVID-19 patients with age-matched healthy donors, we found a strong positive correlation between plasma levels of soluble FasL (sFasL) and T cell surface expression of Fas/CD95 with the propensity of T cells to die and CD4 T cell counts. Plasma levels of sFasL and T cell death are correlated with CXCL10 which is part of the signature of 4 biomarkers of disease severity (ROC, 0.98). We also found that members of the Bcl-2 family had modulated in the T cells of COVID-19 patients. More importantly, we demonstrated that the pan-caspase inhibitor, Q-VD, prevents T cell death by apoptosis and enhances Th1 transcripts. Altogether, our results are compatible with a model in which T-cell apoptosis accounts for T lymphopenia in individuals with severe COVID-19. Therefore, a strategy aimed at blocking caspase activation could be beneficial for preventing immunodeficiency in COVID-19 patients.
Published: 2022

13. Assessment of left ventricular dyssynchrony by speckle tracking echocardiography in children with duchenne muscular dystrophy

Author: Olivier Cazorla, Charlene Bredy, Marie Vincenti, Catherine Barrea, Albano Melli, Alain Lacampagne, Pascal Amedro, Jérémy Fauconnier, Kathleen Lavastre, Pierre Meyer, Lucie Gamon, Audrey Agullo, Nicolas Lanot, Hamouda Abassi, François Rivier, Thibault Mura, Gregoire De La Villeon, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Cliniques Universitaires Saint-Luc [Bruxelles], Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de rythmologie et modélisation cardiaque [Pessac] (IHU Liryc), Herrada, Anthony, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, and UCL - (SLuc) Service de cardiologie pédiatrique
Subjects: Male, medicine.medical_specialty, Cardiac dyssynchrony, Adolescent, Heart Ventricles, Duchenne muscular dystrophy, Heart failure, Speckle tracking echocardiography, Ventricular Dysfunction, Left, Predictive Value of Tests, MESH: Child, Internal medicine, DMD, MESH: Ventricular Dysfunction, Left, MESH: Muscular Dystrophy, Duchenne, medicine, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Child, Ventricular dyssynchrony, Speckle tracking, MESH: Adolescent, MESH: Humans, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Reproducibility of Results, Paediatrics, medicine.disease, MESH: Male, MESH: Predictive Value of Tests, MESH: Prospective Studies, Muscular Dystrophy, Duchenne, MESH: Reproducibility of Results, Echocardiography, Cardiology, MESH: Echocardiography, MESH: Heart Ventricles, business, Cardiology and Cardiovascular Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Purpose-Prognosis of Duchenne muscular dystrophy (DMD) is related to cardiac dysfunction. Two dimensional-speckle tracking echocardiography (2D-STE) has recently emerged as a non-invasive functional biomarker for early detection of DMD-related cardiomyopathy. This study aimed to determine, in DMD children, the existence of a left ventricle (LV) dyssynchrony using 2D-STE analysis.Methods-This prospective controlled study enrolled 25 boys with DMD (mean age 11.0±3.5 years) with normal LV ejection fraction and 50 age-matched controls. Three measures were performed to assess LV mechanical dyssynchrony: the opposing-wall delays (longitudinal and radial analyses), the modified Yu index, and the time-to-peak delays of each segment. Feasibility and reproducibility of 2D-STE dyssynchrony were evaluated. Results-All three mechanical dyssynchrony criteria were significantly higher in the DMD group than in healthy subjects: (1) opposing-wall delays in basal inferoseptal to basal anterolateral segments (61.4±45.3 msec vs. 18.3±50.4 msec, Prespectively) and in mid inferoseptal to mid anterolateral segments (58.6±35.3 msec vs. 42.4±36.4 msec, Prespectively), (2) modified Yu index (33.3±10.1 msec vs. 28.5±8.1 msec, P, respectively), and (3) most of time-to-peak values, especially in basal and mid anterolateral segments. Feasibility was excellent and reliability was moderate to excellent, with ICC values ranging from 0.49 to 0.97.Conclusion-Detection of LV mechanical dyssynchrony using 2D-STE analysis is an easily and reproducible method in pediatrics. The existence of an early LV mechanical dyssynchrony visualized using 2D-STE analysis in children with DMD before the onset of cardiomyopathy represents a perspective for future pediatric drug trials in the DMD-related cardiomyopathy prevention. Clinical Trial Registration-Clinicaltrials.gov NCT02418338. Post-hoc study, registered on April 16, 2015.
Published: 2021

14. Definition of an adapted cut-off for determining low lean tissue mass in older women with obesity: a comparison to current cut-offs

Author: Maïmoun, Laurent, Serrand, Chris, Mura, Thibault, Renard, Eric, Nocca, David, Lefebvre, Patrick, Boudousq, Vincent, Avignon, Antoine, Mariano-Goulart, Denis, Sultan, Ariane, MORNET, Dominique, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Lapeyronie [Montpellier] (CHU), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut Desbrest de santé publique (IDESP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: [SDV] Life Sciences [q-bio], Sarcopenia, Absorptiometry, Photon, Multidisciplinary, [SDV]Life Sciences [q-bio], Body Composition, Humans, Female, Obesity, Aged, Body Mass Index
Abstract: The prevalence of sarcopenia in patients with obesity varies according to the definition used. The purpose of our study was to: (i) determine the prevalence of sarcopenia in terms of lean tissue mass in older women with obesity using the current cut-offs, (ii) redefine a specific cut-off for low lean tissue mass (LLTM), and (iii) re-determine the prevalence of LLTM using this new cut-off. Appendicular lean mass (ALM) and the ALM index [ALM/height2: ALMI(h2)] and ALMI/body mass index [ALMI(BMI)] were determined in 791 women with or without obesity. LLMM prevalence was calculated using the current cut-offs: EWGSOP2: ALM 2) 2; FNIH: ALM 2) 2 and cut-offs newly determined from data provided from young women with obesity. ALM, ALMI(h2) and ALMI(BMI) were lower in older compared to young obese women. Using the current cut-offs, a wide distribution of LLTM prevalence (0 to 29.2%) was observed. When the newly determined cut-offs were applied – i.e., ALM 2) 2, ALMI(BMI) 2) measured)-(2.08 + 0.183*BMI)]/0.72] − the LLTM mass prevalence was 17.37%; 8.47, 14.8 and 12.71%. respectively. This study showed that the current cut-offs for LLTM as criteria for sarcopenia diagnosis are not adapted to the obese population. Although the new “static” cut-offs appeared to be more adapted, a “dynamic” cut-off for ALMI(h2) that took into account the BMI and thus the obesity severity appeared even more relevant.
Published: 2022

15. The interplay between cognition, depression, anxiety, and sleep in primary Sjogren’s syndrome patients

Author: Goulabchand, Radjiv, Castille, Elodie, Navucet, Sophie, Etchecopar‐etchart, Damien, Matos, Aurélie, Maria, Alexandre, Gutierrez, Laure, Le Quellec, Alain, Menjot de Champfleur, Nicolas, Gabelle, Audrey, Guilpain, Philippe, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Institut d’Imagerie Fonctionnelle Humaine [CHU Montpellier] (I2FH), Laboratoire Charles Coulomb (L2C), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: MESH: Fatigue, Sleep Wake Disorders, MESH: Humans, Multidisciplinary, MESH: Anxiety, MESH: Depression, MESH: Sleep, Depression, Autoimmune diseases, MESH: Quality of Life, MESH: Cognition, Anxiety, MESH: Sleep Wake Disorders, MESH: Sjogren's Syndrome, Cognition, Sjogren's Syndrome, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Quality of Life, Humans, Dementia, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Sleep, Fatigue
Abstract: Primary Sjögren’s syndrome (pSS) is an autoimmune disease with frequent neurological involvement. Memory complaints are common, but their precise patterns remain unclear. We wanted to characterize patterns of neurocognitive profiles in pSS patients with cognitive complaints. Only pSS patients with memory complaints were included, prospectively. Cognitive profiles were compiled through a comprehensive cognitive evaluation by neuropsychologists. Evaluations of anxiety, depression, fatigue, sleep disorders and quality of life were performed for testing their interactions with cognitive profiles. All 32 pSS patients showed at least borderline cognitive impairment, and 17 (53%) exhibited a pathological cognitive profile: a hippocampal profile (37%), a dysexecutive profile (22%), and an instrumental profile (16%) (possible overlap). Regarding the secondary objectives: 37% of patients were depressed, and 48% exhibited a mild-to-severe anxiety trait. Sleep disorders were frequent (excessive daytime sleepiness (55%), high risk for sleep apnea (45%), and insomnia (77%)). Cognitive impairments could not be explained alone by anxiety, depression or sleep disorders. Fatigue level was strongly associated with sleep disorders. Our study highlights that cognitive complaints in pSS patients are supported by measurable cognitive impairments, apart from frequently associated disorders such as depression, anxiety or sleep troubles. Sleep disorders should be screened.
Published: 2022

16. Population pharmacokinetic model of irinotecan and its four main metabolites in patients treated with FOLFIRI or FOLFIRINOX regimen

Author: Florence Gattacceca, Alexandre Evrard, Marc Ychou, Laure Deyme, Dominique Barbolosi, Nicole Tubiana-Mathieu, Litaty Mbatchi, Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Limoges, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and GATTACCECA, Florence
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, FOLFIRINOX, Leucovorin, Toxicology, 0302 clinical medicine, CPT-11, Antineoplastic Combined Chemotherapy Protocols, Pharmacology (medical), Population pharmacokinetics, ComputingMilieux_MISCELLANEOUS, education.field_of_study, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Oxaliplatin, 030220 oncology & carcinogenesis, FOLFIRI, Female, Fluorouracil, Folfirinox Regimen, Colorectal Neoplasms, medicine.drug, medicine.medical_specialty, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Context (language use), Irinotecan, Nonlinear mixed effect modelling, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Pharmacokinetics, Internal medicine, medicine, Humans, education, Pharmacology, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, stomatognathic diseases, 030104 developmental biology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Camptothecin, Topoisomerase I Inhibitors, business
Abstract: International audience; PurposeThe aim of the present study was to characterize the pharmacokinetics of irinotecan and its four main metabolites (SN-38, SN-38G, APC and NPC) in metastatic colorectal cancer patients treated with FOLFIRI and FOLFIRINOX regimens and to quantify and explain the inter-individual pharmacokinetic variability in this context.MethodsA multicenter study including 109 metastatic colorectal cancer patients treated with FOLFIRI or FOLFIRINOX regimen, associated or not with a monoclonal antibody, was conducted. Concentrations of irinotecan and its four main metabolites were measured in 506 blood samples during the first cycle of treatment. Collected data were analyzed using the population approach. First, fixed and random effects models were selected using statistical and graphical methods; second, the impact of covariates on pharmacokinetic parameters was evaluated to explain the inter-individual variability in pharmacokinetic parameters.ResultsA seven-compartment model best described the pharmacokinetics of irinotecan and its four main metabolites. First-order rates were assigned to distribution, elimination, and metabolism processes, except for the transformation of irinotecan to NPC which was nonlinear. Addition of a direct conversion of NPC into SN-38 significantly improved the model. Co-administration of oxaliplatin significantly modified the distribution of SN-38.ConclusionTo our knowledge, the present model is the first to allow a simultaneous description of irinotecan pharmacokinetics and of its four main metabolites. Moreover, a direct conversion of NPC into SN-38 had never been described before in a population pharmacokinetic model of irinotecan. The model will be useful to develop pharmacokinetic-pharmacodynamic models relating SN-38 concentrations to efficacy and digestive toxicities.
Published: 2021

17. Low-dose IL-2 in children with recently diagnosed type 1 diabetes: a Phase I/II randomised, double-blind, placebo-controlled, dose-finding study

Author: Michel Polak, Randa Salet, David Klatzmann, Michelle Rosenzwajg, Pierre Bougnères, Caroline Storey, Cecile Bibal, Jean-Claude Carel, Claude Bernard, Jacques Beltrand, Tu-Anh Tran, Agnès Hartemann, Alexandra Roux, Nicolas Tchitchek, Roberta Lorenzon, Chloé Amouyal, Eric Vicaut, Pierre Corbeau, Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [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), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Paris - UFR Médecine [Santé] (UP Médecine), Université de Paris (UP), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), CHU Necker - Enfants Malades [AP-HP], GHU AP-HP Centre Université de Paris, Service de diabétologie [CHU Pitié-Salpétrière], 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 Lariboisière-Fernand-Widal [APHP], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Salvy-Córdoba, Nathalie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), Service de Diabétologie [CHU Pitié-Salpétrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Adolescent, [SDV.IMM] Life Sciences [q-bio]/Immunology, Autoimmune diseases, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Autoimmunity, 030209 endocrinology & metabolism, medicine.disease_cause, Placebo, T-Lymphocytes, Regulatory, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, 0302 clinical medicine, Double-Blind Method, Internal medicine, Insulin Secretion, Injection site reaction, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Insulin, Child, Adverse effect, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Type 1 diabetes, business.industry, Immunotherapy, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, CD4 Lymphocyte Count, 3. Good health, Clinical trial, Diabetes Mellitus, Type 1, 030104 developmental biology, Interleukin-2, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, T1D, business, Tolerance
Abstract: Low-dose IL-2 (ld-IL2) selectively activates and expands regulatory T cells (Tregs) and thus has the potential to skew the regulatory/effector T (Treg/Teff) cell balance towards improved regulation. We investigated which low doses of IL-2 would more effectively and safely activate Tregs during a 1 year treatment in children with recently diagnosed type 1 diabetes. Dose Finding Study of IL-2 at Ultra-low Dose in Children With Recently Diagnosed Type 1 Diabetes (DF-IL2-Child) was a multicentre, double-blinded, placebo-controlled, dose-finding Phase I/II clinical trial conducted in four centres at university hospitals in France: 24 children (7–14 years old) with type 1 diabetes diagnosed within the previous 3 months were randomly assigned 1:1:1:1 to treatment by a centralised randomisation system, leading to a 7/5/6/6 patient distribution of placebo or IL-2 at doses of 0.125, 0.250 or 0.500 million international units (MIU)/m2, given daily for a 5 day course and then fortnightly for 1 year. A study number was attributed to patients by an investigator unaware of the randomisation list and all participants as well as investigators and staff involved in the study conduct and analyses were blinded to treatments. The primary outcome was change in Tregs, expressed as a percentage of CD4+ T cells at day 5. It pre-specified that a ≥60% increase in Tregs from baseline would identify Treg high responders. There were no serious adverse events. Non-serious adverse events (NSAEs) were transient and mild to moderate. In treated patients vs placebo, the commonest NSAE was injection site reaction (37.9% vs 3.4%), whereas other NSAEs were at the same level (23.3% vs 19.2%). ld-IL2 induced a dose-dependent increase in the mean proportion of Tregs, from 23.9% (95% CI −11.8, 59.6) at the lowest to 77.2% (44.7, 109.8) at the highest dose, which was significantly different from placebo for all dose groups. However, the individual Treg responses to IL-2 were variable and fluctuated over time. Seven patients, all among those treated with the 0.250 and 0.500 MIU m−2 day−1 doses, were Treg high responders. At baseline, they had lower Treg proportions in CD4+ cells than Treg low responders, and serum soluble IL-2 receptor α (sIL-2RA) and vascular endothelial growth factor receptor 2 (VEGFR2) levels predicted the Treg response after the 5 day course. There was no significant change in glycaemic control in any of the dose groups compared with placebo. However, there was an improved maintenance of induced C-peptide production at 1 year in the seven Treg high responders as compared with low responders. The safety profile at all doses, the dose-dependent effects on Tregs and the observed variability of the Treg response to ld-IL2 in children with newly diagnosed type 1 diabetes call for use of the highest dose in future developments. The better preservation of insulin production in Treg high responders supports the potential of Tregs in regulating autoimmunity in type 1 diabetes, and warrants pursuing the investigation of ld-IL2 for its treatment and prevention. ClinicalTrials.gov NCT01862120. Assistance Publique-Hopitaux de Paris, Investissements d’Avenir programme (ANR-11-IDEX-0004-02, LabEx Transimmunom and ANR-16-RHUS-0001, RHU iMAP) and European Research Council Advanced Grant (FP7-IDEAS-ERC-322856, TRiPoD).
Published: 2020

18. Characterisation of tumour microenvironment and immune checkpoints in primary central nervous system diffuse large B cell lymphomas

Author: Laura De Oliveira, Valère Cacheux, Melissa Alame, Pascal Roger, Valérie Rigau, Valérie Costes-Martineau, Samia Gonzalez, Marion Pirel, Michel Fabbro, Alicia Tourneret, Luc Durand, Luc Bauchet, Vanessa Szablewski, Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Biopathologie [CHRU Montpellier], Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), and Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)
Subjects: Male, 0301 basic medicine, Programmed Cell Death 1 Receptor, Aggressive lymphoma, B7-H1 Antigen, Central Nervous System Neoplasms, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, Tumor Microenvironment, In Situ Hybridization, Fluorescence, Aged, 80 and over, CD68, General Medicine, Middle Aged, Prognosis, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, France, Lymphoma, Large B-Cell, Diffuse, Adult, Primary central nervous system diffuse large B cell lymphoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Pathology and Forensic Medicine, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, Immune system, PDL1, Biomarkers, Tumor, medicine, Humans, Molecular Biology, B cell, Aged, Retrospective Studies, Tumour microenvironment, Macrophages, Cell Biology, medicine.disease, Immune checkpoint, 030104 developmental biology, Immune checkpoints, Cancer research, PAX5, Diffuse large B-cell lymphoma, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, CD8
Abstract: International audience; Primary central nervous system diffuse large B cell lymphoma (PCNS-DLBCL) is a rare and aggressive entity of diffuse large B cell lymphoma (DLBCL). Elements of the tumour microenvironment (TME) including tumour-infiltrating lymphocytes (TILs) and tumour-associated macrophages (TAMs) have been associated with survival in DLBCL but their composition and prognostic impact in PCNS-DLBCL are unknown. Programmed cell death-1 (PD1)/programmed death-ligand 1 (PD-L1) immune checkpoint may represent a therapeutic option. Here, we aimed to characterise PD1/PDL1 immune checkpoints and the composition of the TME in PCNS-DLBCL. We collected tumour tissue and clinical data from 57 PCNS-DLBCL and used immunohistochemistry to examine TAMs (CD68, CD163), TILs (CD3, CD4, CD8, PD1) and tumour B cells (PAX5/PDL1 double stains, PDL1). The PDL1 gene was evaluated by fluorescence in situ hybridization (FISH). PAX5/PDL1 identified PDL1 expression by tumour B cells in 10/57 cases (17.5%). PDL1 gene translocation was a recurrent cytogenetic alteration in PNCS-DLBCL (8/47.17%) and was correlated with PDL1 positive expression in tumour B cells. The TME consisted predominantly of CD163 (+) M2 TAMs and CD8 (+) TILs. Most TAMs expressed PDL1 and most TILs expressed PD1. The density of TAMs and TILs did not associate with outcome. We showed that expression of PD1 on TILs and PDL1 on TAMs, but not the expression of PDL1 on tumour B cells was correlated with better prognosis. These findings support a significant role of TME composition and PD1/PDL1 crosstalk in PCNS-DLBCL pathogenesis and bring new insights to the targeted therapy of this aggressive lymphoma.
Published: 2019

19. A recurrent SHANK3 frameshift variant in Autism Spectrum Disorder

Author: Mustafa Sahin, Jacob A. S. Vorstman, Delnaz Roshandel, Alana Iaboni, Iva Pritišanac, Richard Delorme, Stephen W. Scherer, Marjolaine Willems, Mehdi Zarrei, Lynette Lau, Jennifer L. Howe, Alan M. Moses, Evdokia Anagnostou, Brianna Godlewski, Livia O Loureiro, Miriam S. Reuter, Julie D. Forman-Kay, Anne-Claude Tabet, Siddharth Srivastava, Brett Trost, Suzanne M E Lewis, Christian R. Marshall, Olivia Rennie, Thomas W. Frazier, Peter Szatmari, Thomas Bourgeron, Elizabeth D. Buttermore, Kristina Calli, Stelios Georgiades, Amélie Piton, Dean Hartley, Clarrisa A Lisa Bradley, James Lespinasse, Serge Lumbroso, The Hospital for sick children [Toronto] (SickKids), Holland Bloorview Kids Rehabilitation Hospital [Toronto, ON, Canada], University of British Columbia (UBC), University of Toronto, Department of Biochemistry [University of Toronto], Harvard Medical School [Boston] (HMS), John Carroll University, McMaster University [Hamilton, Ontario], Centre for Addiction and Mental Health [Toronto] (CAMH), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Métropole Savoie [Chambéry], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre for Integrative Biology - CBI (Inserm U964 - CNRS UMR7104 - IGBMC), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), CHU Strasbourg, This work was funded by Autism Speaks, Autism Speaks Canada, the University of Toronto McLaughlin Centre, the Canada Foundation for Innovation, the Canadian Institutes of Health Research (CIHR), Genome Canada/Ontario Genomics Institute, the Government of Ontario, Brain Canada, Ontario Brain Institute Province of Ontario Neurodevelopmental Disorders (POND), and The Hospital for Sick Children Foundation. L.O.L holds Lap-Chee Tsui Postdoctoral Fellowship from The Hospital for Sick Children. S.W.S holds the Northbridge Chair in Paediatric Research at the Hospital for Sick Children and University of Toronto., and Retiveau, Nolwenn
Subjects: Proband, Genetic counseling, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, QH426-470, Biology, behavioral disciplines and activities, Article, Frameshift mutation, 03 medical and health sciences, 0302 clinical medicine, Genotype-phenotype distinction, mental disorders, Gene duplication, Genetics, medicine, Copy-number variation, Molecular Biology, Genetics (clinical), 030304 developmental biology, 0303 health sciences, medicine.disease, Phenotype, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Autism spectrum disorder, Medicine, Medical genomics, 030217 neurology & neurosurgery
Abstract: Autism Spectrum Disorder (ASD) is genetically complex with ~100 copy number variants and genes involved. To try to establish more definitive genotype and phenotype correlations in ASD, we searched genome sequence data, and the literature, for recurrent predicted damaging sequence-level variants affecting single genes. We identified 18 individuals from 16 unrelated families carrying a heterozygous guanine duplication (c.3679dup; p.Ala1227Glyfs*69) occurring within a string of 8 guanines (genomic location [hg38]g.50,721,512dup) affecting SHANK3, a prototypical ASD gene (0.08% of ASD-affected individuals carried the predicted p.Ala1227Glyfs*69 frameshift variant). Most probands carried de novo mutations, but five individuals in three families inherited it through somatic mosaicism. We scrutinized the phenotype of p.Ala1227Glyfs*69 carriers, and while everyone (17/17) formally tested for ASD carried a diagnosis, there was the variable expression of core ASD features both within and between families. Defining such recurrent mutational mechanisms underlying an ASD outcome is important for genetic counseling and early intervention.
Published: 2021

20. Fluid management and risk factors for renal dysfunction in patients with severe sepsis and/or septic shock

Author: Jérôme Larché, Gilles Motte, Jean-Michel Constantin, Marc Leone, Bernard Allaouchiche, Laurent Favier, Sandrine Alonso, Laurent Muller, Sonia Lazarovici, Nicolas Molinari, Jean-Yves Lefrant, Carey M. Suehs, Samir Jaber, Luc Jacques, Div Anesthesie Reanimat Douleur Urgences, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Laboratoire d'Anatomie [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hop St Eloi, Serv Anesthesie Reanimat B, Mathématiques, Informatique et STatistique pour l'Environnement et l'Agronomie (MISTEA), Institut National de la Recherche Agronomique (INRA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Laboratoire de Biostatistique, Epidémiologie clinique, Santé Publique Innovation et Méthodologie [CHU Nîmes] (BESPIM), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service Réanimation, Centre Hospitalier de Béziers, Service Réanimation Polyvalente, Centre Hospitalier de Narbonne, Centre Hospitalier Saint Jean de Perpignan, Centre Hospitalier de Carcassonne, Hôpitaux du Bassin de Thau, Serv Biostat Epidemiol Clin Sante Publ Informat M, Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Service Réanimation Adultes, CHU Clermont-Ferrand, Hôpital Edouard Herriot, Service Anesthésie Réanimation, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Faculté de Médecine, Université Montpellier 1 (UM1), Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA), Centre hospitalier Intercommunal du Bassin de Thau, Centre Hospitalier Universitaire de Clermont-Ferrand, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)
Subjects: medicine.medical_specialty, medicine.medical_treatment, Médecine humaine et pathologie, médecine humaine, urologic and male genital diseases, Critical Care and Intensive Care Medicine, Sepsis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, 030202 anesthesiology, Internal medicine, statistique appliquée, medicine, Renal replacement therapy, Creatinine, Kidney, Septic shock, business.industry, estimation du risque, Acute kidney injury, 030208 emergency & critical care medicine, medicine.disease, 3. Good health, Surgery, medicine.anatomical_structure, chemistry, Shock (circulatory), Human health and pathology, SOFA score, maladie rénale, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Introduction: The causative role of new hydroxyethyl starch (HES 130/0.4) in renal dysfunction frequency (a > 50% increase in serum creatinine or need for renal replacement therapy (RRT)) remains debated. Using the database of a multicenter study focusing on patients with severe sepsis and septic shock, the present study aimed at identifying factors associated with the occurrence of renal dysfunction. Methods: Among the 435 patients in a multicenter study of patients with severe sepsis and septic shock in 15 Southern French ICUs, 388 patients surviving after 24 hour, without a history of renal failure were included. Factors associated with renal dysfunction and RRT were isolated using a multivariate analysis with logistic regression. Results: Renal dysfunction was reported in 117 (33%) patients. Ninety patients required RRT. Among study participants, 379 (98%) were administered fluids in the first 24 hours of management: HES 130/0.4 only (n = 39), crystalloids only (n = 63), or both HES 130/0.4 and crystalloids (n = 276). RRT was independently associated with the need for vasopressors and the baseline value of serum creatinine in the first 24 hours. Multivariate analysis indicated that male gender, SAPS II score, being a surgical patient, lack of decrease in SOFA score during the first 24 hours, and the interventional period of the study were independently associated with renal dysfunction. Mortality increased in the presence of renal dysfunction (48% versus 24%, P < 0.01). Conclusions: Despite being used in more than 80% of patients with severe sepsis and/or septic shock, the administration of HES 130/0.4 in the first 24 hours of management was not associated with the occurrence of renal dysfunction.
Published: 2012

21. Impact of Metastasis Surgery and Alkylating-Agent-Based Chemotherapy on Outcomes of Metastatic Malignant Phyllodes Tumors: A Multicenter Retrospective Study

Author: Jean-Yves Blay, Charles Honoré, Marick Laé, Audrey Monneur, Mehdi Brahmi, Fabien Reyal, Nicolas Isambert, Camille Chakiba, Esma Saada-Bouzid, Sophie Piperno-Neumann, Thomas Ryckewaert, Nelly Firmin, S. Thezenas, Christophe Sajous, Nicolas Penel, Sébastien Salas, Mathias Neron, Isabelle Ray-Coquard, François Bertucci, Florence Duffaud, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Unité de biostatistiques, CRLCC Val d'Aurelle - Paul Lamarque, Institut Curie [Paris], Département de recherche translationnelle, Département d'oncologie médicale, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Institut Gustave Roussy (IGR), Pôle chirurgical et interventionnel [Gustave Roussy], Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Medical Oncology Unit, S. Camillo-Forlanini Hospital, Service d’Oncologie Médicale [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre Léon Bérard [Lyon], Service d'Oncologie Médicale, Département d'oncologie Médicale, Département de Recherche Translationnelle, Université de Lille-UNICANCER, Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)
Subjects: Adult, Male, Alkylating Agents, medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Breast Neoplasms, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Metastasis, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Phyllodes Tumor, Surgical oncology, medicine, Humans, Neoplasm Metastasis, Aged, Retrospective Studies, Aged, 80 and over, Chemotherapy, business.industry, Hazard ratio, Retrospective cohort study, Middle Aged, Prognosis, medicine.disease, Survival Analysis, Confidence interval, 3. Good health, Surgery, Radiation therapy, Oncology, Chemotherapy, Adjuvant, Surgical Procedures, Operative, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, France, Sarcoma, business
Abstract: Metastatic phyllodes tumors have poor prognosis with median overall survival of 11.5 months. The objective of this study is to identify prognostic factors and the best options for management of metastatic malignant phyllode tumors (MMPTs). A multicentric retrospective study, including cases of MMPT from 10 sarcoma centers, was conducted. The primary end-point was overall survival (OS), and the secondary end-point was the clinical benefit of chemotherapy (CBCT) rate. 51 MMPT patients were included. Median time from diagnosis to metastatic recurrence was 13 months. Management of MMPT consisted in surgery of the metastatic disease for 16 patients (31.3%), radiation therapy of the metastatic disease for 15 patients (31.9%), and chemotherapy for 37 patients (72.5%). Median follow-up was 62.1 months [95% confidence interval (CI) 31–80 months]. Median OS was 11.5 months (95% CI 7.5–18.7 months). On multivariate analysis, two or more metastatic sites [hazard ratio (HR) 2.81, 95% CI 1.27–6.19; p = 0.01] and surgery of metastasis (HR 0.33, 95% CI 0.14–0.78; p = 0.01) were independently associated with OS. The CBCT rate was 31.4% and 16.7% for the first and second lines. Polychemotherapy was not superior to single-agent therapy. Alkylating-agent-based chemotherapy, possibly associated with anthracyclines, was associated with a better CBCT rate than anthracyclines alone (p = 0.049). The results of this study emphasize the impact of the number of metastatic sites on survival of MMPT patients and the leading role of metastasis surgery in MMPT management. If systemic therapy is used, it should include alkylating agents, which are associated with a better clinical benefit.
Published: 2019

22. Optimization of radiation dose for CT detection of lytic and sclerotic bone lesions: a phantom study

Author: Ahmed Larbi, Fabricio Pereira, Aymeric Hamard, J. Frandon, Joël Greffier, Jean Paul Beregi, Patrick Omoumi, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), and Lausanne University Hospital
Subjects: MESH: Radiation Dosage, medicine.medical_specialty, Image quality, Bone Neoplasms, MESH: Algorithms, Image processing, Iterative reconstruction, Radiation Dosage, Imaging phantom, Pelvis, 030218 nuclear medicine & medical imaging, Multidetector computed tomography, MESH: Lumbar Vertebrae, 03 medical and health sciences, 0302 clinical medicine, MESH: Radiographic Image Interpretation, Computer-Assisted, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Humans, Radiology, Nuclear Medicine and imaging, Neuroradiology, MESH: Pelvis, Lumbar Vertebrae, MESH: Humans, Phantoms, Imaging, business.industry, Ultrasound, Reproducibility of Results, General Medicine, MESH: Bone Neoplasms, Spine, MESH: Reproducibility of Results, MESH: Phantoms, Imaging, 030220 oncology & carcinogenesis, Image enhancement, Image reconstruction, Radiographic Image Interpretation, Computer-Assisted, Tomography, Radiology, Tomography, X-Ray Computed, MESH: Tomography, X-Ray Computed, business, Quality assurance, Algorithms
Abstract: To determine the best compromise between low radiation dose and suitable image quality for the detection of lytic and sclerotic bone lesions of the lumbar spine and pelvis. A phantom was scanned using the routine protocol (STD, 13 mGy) and six decreasing dose levels. Raw data were reconstructed using level 3 of iterative reconstruction (IR3) with 1-mm slice thickness for the STD protocol and highest IR levels with 3-mm slice thickness for the others. CTDIvol was used for radiation dose assessment. Quantitative criteria (noise power spectrum [NPS], task-based transfer function [TTF], and the detectability index [d′]), as well as qualitative analysis, were used to compare protocols. NPS and TTF were computed using specific software (imQuest). d′ was computed for two imaging tasks: lytic and sclerotic bone lesions. A subjective analysis was performed to validate the image quality obtained on the anthropomorphic phantom with the different dose values. Similar d′ values were found for CTDIvol from 3 to 4 mGy with IR4 and from 1 to 2 mGy for IR5 compared with d′ values using the STD protocol. Image quality was validated subjectively for IR4 but rejected for IR5 (image smoothing). Finally, for the same d′, the dose was reduced by 74% compared with the STD protocol, with the CTDIvol being 3.4 mGy for the lumbar spine and for the pelvis. A dose level as low as 3.4 mGy, in association with high levels of IR, provides suitable image quality for the detection of lytic and sclerotic bone lesions of the lumbar spine and pelvis. • A CTDI vol of 3.4 mGy, in association with high iterative reconstruction level, provides suitable image quality for the detection of lytic and sclerotic bone lesions, both at objective and subjective analysis. • Compared with the standard protocol, radiation dose can be reduced up to 74% for the lumbar spine and pelvis. • A task-based image quality assessment using the detectability index represents an objective method for the assessment of image quality and bridges the gap between complex physical metrics and subjective image analysis.
Published: 2019

23. Clinical interest of PD-L1 immuno-histochemistry expression as a predictive factor of Bacillus Calmette Guerin (BCG) efficacy in refractory high-risk non-muscle-invasive bladder cancer (NMIBC)

Author: Clara Delcourt, Andre Gillibert, François Xavier Nouhaud, Jacques Irani, Christian Pfister, Françoise Gobet, Pierre Gemival, Jean Christophe Sabourin, Sophie Ferlicot, Service d'urologie [Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Département de Pathologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Unité de biostatistiques [CHU Rouen], Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen]-CHU Rouen, and Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, PD-L1, Nephrology, medicine.medical_specialty, Urology, 030232 urology & nephrology, Clone (cell biology), Risk Assessment, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Gastroenterology, B7-H1 Antigen, Cohort Studies, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Immune system, Adjuvants, Immunologic, Refractory, Predictive Value of Tests, Internal medicine, medicine, Humans, Neoplasm Invasiveness, BCG, Fisher's exact test, Aged, Retrospective Studies, Aged, 80 and over, Bladder cancer, biology, business.industry, Middle Aged, medicine.disease, Immunohistochemistry, 3. Good health, Predictive factor, Treatment Outcome, Urinary Bladder Neoplasms, 030220 oncology & carcinogenesis, BCG Vaccine, symbols, biology.protein, Female, business
Abstract: International audience; Objective: To assess PD-L1 expression in tumor (TC) and tumor infiltrating immune cells (IC) as a predictive factor of BCG therapy failure in high-risk NMIBC.Materials and methods: Patients treated with complete resection followed by bladder BCG instillation for high-risk NMIBC were included. Early recurrence (ER) was defined as tumor recurrence after BCG induction course. The association between ER and immuno-histochemistry PD-L1 (E1L3N clone) expression by tumors cells (TC) and tumor infiltrating immune cells (IC) was investigated using an exact Fisher test variant.Results: A total of 186 patients were included, of whom 38 (20.4%) were ER, 35 (18.8%) were positive for TC PD-L1 expression and 60 (32.3%) were positive for IC PD-L1. ER was not significantly (p = 0.97) more frequent in the TC PD-L1 ≥ 1% group (n = 7, 20.0%) than in the TC PD-L1-negative group (n = 31, 20.5%). Patients with IC PD-L1 negative had ER in 15 (19.2%) cases and patients with IC PD-L1 ≥ 1% had ER in 23 (21.3%) cases. PD-L1-positive expression for IC (threshold > 1%) was correlated with immune infiltrate density (95.2% dense immune infiltrate vs 47.2% low immune infiltrate, p < 0.05), with increased expression of PD-L1 by IC after BCG therapy (p = 0.006).Conclusion: No association was observed between immuno-histochemistry PD-L1 positivity and ER after BCG therapy. Nevertheless, the relationship between immune infiltrate and PD-L1 positivity confirmed the interest of assessing the immune infiltrate density to define tumor's profile.
Published: 2019

24. Glutathione-dependent enzyme activities of peripheral blood mononuclear cells decrease during the winter season compared with the summer in normal-weight and severely obese adolescents

Author: Enrique Roche, Vicente Micol, Maria Herranz, Agnès Vinet, Néstor Vicente-Salar, Antonia Perez-Martin, Guillaume Walther, David Montero, Universidad Miguel Hernández [Elche] (UMH), EA4278 Laboratoire de Pharm-Ecologie Cardiovasculaire (LaPEC), Avignon Université (AU), Instituto de Salud Carlos III [Madrid] (ISC), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), and Université Montpellier 1 (UM1)-Université de Montpellier (UM)
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Antioxidant, Adolescent, Physiology, medicine.medical_treatment, Glutathione reductase, 030209 endocrinology & metabolism, Biochemistry, Peripheral blood mononuclear cell, Antioxidants, Superoxide dismutase, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Weight loss, Internal medicine, medicine, Vitamin D and neurology, Humans, Obesity, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], 2. Zero hunger, chemistry.chemical_classification, biology, business.industry, Glutathione peroxidase, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Seasonality, General Medicine, Glutathione, Enzymes, 3. Good health, 030104 developmental biology, Endocrinology, chemistry, Antioxidants, Glutathione peroxidase, Glutathione reductase, Obesity, Seasonality, biology.protein, Female, Seasons, medicine.symptom, business
Abstract: International audience; Oxidative stress-related inflammation is known to play a vital role in obesity-associated cardiovascular disease, contributing to the early stages of the pathology as well as during its development. Therefore, it is of great interest to understand how obesity-induced stress modulates antioxidant enzyme activity during puberty. To this end, 27 severely obese adolescents (body mass index > 30, z-score > 3.7) were recruited from a paediatric weight management centre. Eighteen were recruited during the summer and nine in the winter. All underwent a 4-month weight loss programme consisting in diet and physical activity. Twenty normal-weight age-matched adolescents were recruited from the same geographical area to serve as controls. Blood samples were extracted, and antioxidant enzyme activities were determined in peripheral blood mononuclear cells (PBMCs) and erythrocytes. The enzymes studied included catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase. Severely obese adolescents presented lower PBMC-glutathione reductase activity than their corresponding normal-weight counterparts. In addition, glutathione-dependent activities tended to be lower in both groups during the winter compared with summer. These changes coincided with differences in circulating vitamin D levels. Results may suggest that season-dependent factors such as vitamin D could affect glutathione-dependent activities in severely obese as well as in normal-weight adolescents.
Published: 2019

25. Long-term anatomic and functional results of laparoscopic sacrocolpopexy: a prospective study

Author: Stéphane Droupy, A. Chevrot, Elisabeth Llinares, Pierre Costa, Laurent Wagner, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), and Université de Montpellier (UM)
Subjects: Sacrum, medicine.medical_specialty, Time Factors, [SDV]Life Sciences [q-bio], Urology, medicine.medical_treatment, 030232 urology & nephrology, Physical examination, 030204 cardiovascular system & hematology, Prosthesis, Pelvic Organ Prolapse, 03 medical and health sciences, Gynecologic Surgical Procedures, 0302 clinical medicine, Quality of life, medicine, Humans, Prospective Studies, Stage (cooking), Laparoscopy, Prospective cohort study, medicine.diagnostic_test, business.industry, Middle Aged, 3. Good health, Surgery, Treatment Outcome, Nephrology, Vagina, Quality of Life, Female, Sexual function, Complication, business, Sexuality
Abstract: International audience; Purpose The aim of our study was to assess the impact of laparoscopic sacrocolpopexy on pelvic symptoms, quality of life and sexual function in patients with symptomatic pelvic organ prolapse. Secondary goals included the assessment of anatomical correction, recurrence and complication rates. Methods This is a prospective, single-center study that included 82 patients between 2009 and 2016. A clinical evaluation took place before surgery, and was repeated at 3, 12, 36 and 60 months postoperatively. Patients routinely received an anterior prosthesis, associated with a posterior prosthesis in case of symptomatic rectocele. Patients included self-administered questionnaires for functional pelvic problems (PFDI-20), quality of life (PFIQ-7), and sexual function (PISQ-12), and a clinical examination with POP-Q staging, at each medical visit. Results Functional pelvic problems derived from prolapse (PFDI-20 scores) and their impact on patients’ quality of life (PFIQ-7 score) significantly improved at 3, 12, 36 and 60 months postoperatively. Improvement on sexual activity was significant at 3 and 60 months postoperatively. Effective prolapse anatomical correction (POP-Q score
Published: 2019

26. Fortuitous discovery of non-fluorocholine-fixing papillary carcinoma of vesicular variant of the thyroid

Author: Guillaume Chambon, Benjamin Lallemant, Nicolas Guignard, Yaser Najaf, Benjamin Chambert, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), and Service de Médecine Nucléaire [Nîmes]
Subjects: Male, Thyroid nodules, endocrine system, medicine.medical_specialty, endocrine system diseases, [SDV]Life Sciences [q-bio], Scintigraphy, Choline, Thyroid carcinoma, 03 medical and health sciences, 0302 clinical medicine, Positron Emission Tomography Computed Tomography, medicine, Humans, Thyroid Neoplasms, 030223 otorhinolaryngology, Aged, Parathyroid adenoma, Incidental Findings, PET-CT, medicine.diagnostic_test, business.industry, Thyroid, General Medicine, Middle Aged, medicine.disease, medicine.anatomical_structure, Fine-needle aspiration, Otorhinolaryngology, Thyroid Cancer, Papillary, 030220 oncology & carcinogenesis, Female, Radiology, Radiopharmaceuticals, business, Primary hyperparathyroidism
Abstract: International audience; Purpose Characterization of thyroid nodules is crucial to propose surgical intervention for histological verification. Cervical ultrasound potentially combined with fine needle aspiration is recommended, and fluorocholine positron emission tomography (FCH-PET), commonly used in prostatic cancers, has been evaluated in the diagnosis of thyroid cancers in recent publications. Methods We present two cases of patients with multinodular thyroid and primary hyperparathyroidism. The preoperative assessment consisted of an ultrasound, a MIBI scintigraphy and an FCH-PET in favor of a parathyroid adenoma. Results The imaging examinations pointed to a diagnosis of a parathyroid adenoma. In both cases, papillary thyroid carcinoma, missed by FCH-PET, was discovered incidentally at a distance from the parathyroid adenoma during the surgical procedure. Conclusions These are the first descriptions of thyroid papillary carcinoma without preoperative FCH-PET identification. These clinical cases are contrary to recent publications showing a benefit of this examination in the diagnosis of thyroid cancers.
Published: 2019

27. Do Patients need Lifelong β-Blockers after an Uncomplicated Myocardial Infarction?

Author: Johanne Silvain, Benoit Lattuca, Mathieu Kerneis, Michel Zeitouni, Paul Guedeney, Guillaume Cayla, Gilles Montalescot, Jean-Philippe Collet, Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), and Université de Montpellier (UM)
Subjects: medicine.medical_specialty, Time Factors, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Adrenergic beta-Antagonists, Myocardial Infarction, MEDLINE, 030204 cardiovascular system & hematology, Revascularization, law.invention, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Quality of life, Randomized controlled trial, law, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Myocardial infarction, Medical prescription, Intensive care medicine, Heart Failure, business.industry, General Medicine, medicine.disease, 3. Good health, Hospitalization, Heart failure, Quality of Life, Cardiology and Cardiovascular Medicine, business
Abstract: International audience; The lifelong use of β-adrenoceptor antagonists (β-blockers) after a myocardial infarction (MI) has been the standard of care based on trials performed before the era of revascularization, when heart failure was common. Large randomized trials in the mid-1980s demonstrated that β-blockers played a major role in improving the in-hospital and long-term survival of patients admitted for MI. However, the implementation of rapid myocardial reperfusion led to a substantial survival benefit and a reduction of heart failure because of reduced infarct size. Modern large longitudinal registries did not provide sufficient evidence to support long-term β-blocker therapy in patients with uncomplicated acute MI. The long-term prescription of this therapy has become a matter of debate given the lack of contemporary evidence, frequent side effects, and treatment adherence issues. Furthermore, this shift into the reperfusion era led to a downgraded recommendation for the use of β-blockers in post-MI patients (class IIa B recommendation) in the 2017 European Society of Cardiology (ESC) recommendations for the treatment of ST-segment elevation MI (STEMI). Three large ongoing multicenter randomized trials (AβYSS, REDUCE-SWEDEHEART, and REBOOT-CNIC) are evaluating early discontinuation of β-blockers after an uncomplicated acute MI. The tested hypothesis is that β-blocker withdrawal is safe versus major adverse cardiovascular events and improves quality of life by reducing side effects. Thus, the present review summarizes the exhaustive evidence-based data for long-term β-blocker use after uncomplicated MI and the ongoing trials.
Published: 2019

28. Subarachnoid extension of lobar hemorrhage on acute/subacute MRI is associated with cerebral amyloid angiopathy criteria

Author: Lavinia Tatu, Eric Thouvenot, Dimitri Renard, Teodora Parvu, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Génomique Fonctionnelle (IGF), and 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)
Subjects: Male, medicine.medical_specialty, Siderosis, Subarachnoid hemorrhage, Neurology, [SDV]Life Sciences [q-bio], Fluid-attenuated inversion recovery, Subarachnoid Space, 03 medical and health sciences, 0302 clinical medicine, mental disorders, medicine, Humans, 030212 general & internal medicine, 10. No inequality, Aged, Cerebral Hemorrhage, Neuroradiology, Aged, 80 and over, Intracerebral hemorrhage, business.industry, General Medicine, Middle Aged, Subarachnoid Hemorrhage, medicine.disease, Magnetic Resonance Imaging, Superficial siderosis, 3. Good health, Cerebral Amyloid Angiopathy, Etiology, Female, Neurology (clinical), Cerebral amyloid angiopathy, Radiology, business, 030217 neurology & neurosurgery
Abstract: Subarachnoid hemorrhage extension (SAHE) in the acute phase of cerebral amyloid angiopathy (CAA)-related lobar hemorrhage (LH) assessed by CT is very frequent. Recently, SAHE, together with finger-like projections on CT and ApoE4, has been used in a prediction model for histopathologically proven CAA showing excellent discrimination. Our aim was to analyze SAHE on MRI in the acute and subacute phase of LH in patients with and without associated hemorrhagic features supportive of CAA (i.e. chronic LH, cortical superficial siderosis [CSS], and strictly lobar cerebral microbleeds [CMB]). We retrospectively studied SAHE on MRI performed in the acute and subacute phase (within 21 days) in a cohort of consecutive patients with acute LH recruited between January 2012 and April 2018. Sixty-eight acute LH patients (35 men and 33 women, mean age 74 [range 50-89]) were analyzed. Mean delay between symptom onset and MRI was 3.8 days, and 32 patients underwent MRI within 24 h. Based on MRI, 51 patients were classified as probable CAA and 17 patients without probable CAA. Both groups were comparable regarding age, sex, time of MRI performance, MRI field strength, and acute LH volume. Overall, SAHE was observed in 46 (68%) patients, including 39 (76%) patients with probable CAA and 7 (41%) patients without probable CAA (p = 0.015). SAHE presence was also associated with larger LH volumes. During the work-up in the acute/subacute phase of patients with acute LH, in addition to T2*-weighted imaging in search for other hemorrhagic features (chronic LH, CSS, or lobar CMB) evoking probable underlying CAA etiology, search for SAHE on adapted MRI sequences (FLAIR and T2*-weighted imaging) seems to be interesting because of the association with the presence of probable CAA criteria.
Published: 2018

29. Association of patterns of care, prognostic factors, and use of radiotherapy–temozolomide therapy with survival in patients with newly diagnosed glioblastoma: a French national population-based study

Author: Faiza Bessaoud, Johan Pallud, Sonia Zouaoui, Valérie Rigau, Hugues Duffau, Adeline Riondel, Brigitte Trétarre, Pascale Fabbro-Peray, Emmanuel Mandonnet, Luc Taillandier, M. Charissoux, Amélie Darlix, Dominique Figarella-Branger, Hélène Mathieu-Daudé, L. Bauchet, Elodie Sorbets, Fabienne Bauchet, Michel Fabbro, Aymeric Amelot, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut du Cancer de Montpellier (ICM), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'ophthalmologie [CHU Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Hôpital Lariboisière-Fernand-Widal [APHP], CHU Marseille, Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Gui de Chauliac [Montpellier], Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)
Subjects: Male, Oncology, Cancer Research, Databases, Factual, medicine.medical_treatment, 0302 clinical medicine, Risk of mortality, Practice Patterns, Physicians', Aged, 80 and over, education.field_of_study, Brain Neoplasms, Middle Aged, Prognosis, Combined Modality Therapy, 3. Good health, Survival Rate, Neurology, 030220 oncology & carcinogenesis, Female, France, Neurosurgery, medicine.drug, Cohort study, Adult, medicine.medical_specialty, Population, 03 medical and health sciences, Internal medicine, Neuro-oncology, Temozolomide, medicine, Humans, education, Antineoplastic Agents, Alkylating, Population-based study, Aged, business.industry, Clinical epidemiology, Confidence interval, Radiation therapy, Concomitant, Clinical Study, Neurology (clinical), Glioblastoma, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: Background Glioblastoma is the most frequent primary malignant brain tumor. In daily practice and at whole country level, oncological care management for glioblastoma patients is not completely known. Objectives To describe oncological patterns of care, prognostic factors, and survival for all patients in France with newly-diagnosed and histologically confirmed glioblastoma, and evaluate the impact of extended temozolomide use at the population level. Methods Nationwide population-based cohort study including all patients with newly-diagnosed and histologically confirmed glioblastoma in France in 2008 and followed until 2015. Results Data from 2053 glioblastoma patients were analyzed (male/female ratio 1.5, median age 64 years). Median overall survival (OS) was 11.2 [95% confidence interval (CI) 10.7–11.9] months. The first-line therapy and corresponding median survival (MS, in months) were: 13% did not receive any oncological treatment (biopsy only) (MS = 1.8, 95% CI 1.6–2.1), 27% received treatment without the combination of radiotherapy (RT)–temozolomide (MS = 5.9, 95% CI 5.5–6.6), 60% received treatment including the initiation of the concomitant phase of RT–temozolomide (MS = 16.4, 95% CI 15.2–17.4) whom 44% of patients initiated the temozolomide adjuvant phase (MS = 18.9, 95% CI 18.0–19.8). Only 22% patients received 6 cycles or more of adjuvant temozolomide (MS = 25.5, 95% CI 24.0–28.3). The multivariate analysis showed that the risk of mortality was significantly higher for the non-progressive patients who stopped at 6 cycles (standard protocol) than those who continued the treatment, hazard ratio = 1.5 (95% CI 1.2–1.9). Conclusion In non-progressive patients, prolonging the adjuvant temozolomide beyond 6 cycles may improve OS. Electronic supplementary material The online version of this article (10.1007/s11060-018-03065-z) contains supplementary material, which is available to authorized users.
Published: 2018

30. Effectiveness of early switching from intravenous to oral antibiotic therapy in Staphylococcus aureus prosthetic bone and joint or orthopedic metalware-associated infections

Author: Pascal Kouyoumdjian, Albert Sotto, J. Crouzet, Hélène Boclé, Jean-Philippe Lavigne, Nicolas Cellier, Paul Loubet, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université de Montpellier (UM), Virulence bactérienne et maladies infectieuses (VBMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Malbec, Odile
Subjects: Adult, Male, Methicillin-Resistant Staphylococcus aureus, Staphylococcus aureus, medicine.medical_specialty, Prosthesis-Related Infections, lcsh:Diseases of the musculoskeletal system, Sports medicine, medicine.drug_class, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Antibiotics, medicine.disease_cause, Intravenous antibiotic treatment, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, Epidemiology, medicine, Humans, Orthopedics and Sports Medicine, Oral antibiotic treatment, 030212 general & internal medicine, Retrospective Studies, Prosthetic bone and joint infections, 0303 health sciences, 030306 microbiology, Proportional hazards model, business.industry, Middle Aged, Staphylococcal Infections, Anti-Bacterial Agents, 3. Good health, [SDV] Life Sciences [q-bio], Intravenous therapy, Orthopedic surgery, Female, lcsh:RC925-935, business, Research Article
Abstract: Background The optimal duration of intravenous antibiotic therapy in Staphylococcus aureus prosthetic bone and joint infection has not been established. The objective of this study was to compare the effect of early and late intravenous-to-oral antibiotic switch on treatment failure. Patients and methods We retrospectively analyzed all adult cases of S. aureus prosthetic bone and joint or orthopedic metalware-associated infection between January 2008 and December 2015 in a French university hospital. The primary outcome was treatment failure defined as the recurrence of S. aureus prosthetic bone and joint or orthopedic metalware-associated infection at any time during or after the first line of medical and surgical treatment within 2 years of follow-up. A Cox model was created to assess risk factors for treatment failure. Results Among the 140 patients included, mean age was 60.4 years (SD 20.2), and 66% were male (n = 92). Most infections were due to methicillin-susceptible S. aureus (n = 113, 81%). The mean duration of intravenous antibiotic treatment was 4.1 days (SD 4.6). The majority of patients (119, 85%) had ≤5 days of intravenous therapy. Twelve patients (8.5%) experienced treatment failure. Methicillin-resistant S. aureus infections (HR 11.1; 95% CI 1.5–111.1; p = 0.02), obesity (BMI > 30 kg/m2) (HR 6.9; 95% CI1.4–34.4, p = 0.02) and non-conventional empiric antibiotic therapy (HR 7.1; 95% CI 1.8–25.2; p = 0.005) were significantly associated with treatment failure, whereas duration of intravenous antibiotic therapy (≤ 5 or > 5 days) was not. Conclusion There was a low treatment failure rate in patients with S. aureus prosthetic bone and joint or orthopedic metalware-associated infection with early oral switch from intravenous to oral antibiotic therapy.
Published: 2021

31. Cerebrospinal fluid A beta 1–40 peptides increase in Alzheimer’s disease and are highly correlated with phospho-tau in control individuals

Author: Lehmann, Sylvain, Dumurgier, Julien, Ayrignac, Xavier, Marelli, Cecilia, Alcolea, Daniel, Fortea, Juan, Thouvenot, Eric, Delaby, Constance, Hirtz, Christophe, Vialaret, Jérôme, Ginestet, Nelly, Bouaziz-Amar, Elodie, Laplanche, Jean-Louis, Labauge, Pierre, Paquet, Claire, Lleó, Alberto, Gabelle, Audrey, Universitat Autònoma de Barcelona, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Universitat Autònoma de Barcelona (UAB), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Centre Mémoire de Ressources et de Recherches (CMRR), Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and Salvy-Córdoba, Nathalie
Subjects: medicine.medical_specialty, Neurology, Amyloid, Amyloid peptides, Cognitive Neuroscience, Peptide, Context (language use), Disease, lcsh:RC346-429, Phospho tau, lcsh:RC321-571, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Alzheimer Disease, Internal medicine, Linear regression, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, Tau proteins, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Risk factor, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:Neurology. Diseases of the nervous system, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Amyloid beta-Peptides, Cerebrospinal fluid (CSF), business.industry, Research, Odds ratio, Alzheimer's disease, Peptide Fragments, Endocrinology, chemistry, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, Alzheimer’s disease, Biomarkers, 030217 neurology & neurosurgery
Abstract: Background Amyloid pathology, which is one of the characteristics of Alzheimer’s disease (AD), results from altered metabolism of the beta-amyloid (Aβ) peptide in terms of synthesis, clearance, or aggregation. A decrease in cerebrospinal fluid (CSF) level Aβ1–42 is evident in AD, and the CSF ratio Aβ42/Aβ40 has recently been identified as one of the most reliable diagnostic biomarkers of amyloid pathology. Variations in inter-individual levels of Aβ1–40 in the CSF have been observed in the past, but their origins remain unclear. In addition, the variation of Aβ40 in the context of AD studied in several studies has yielded conflicting results. Methods Here, we analyzed the levels of Aβ1–40 using multicenter data obtained on 2466 samples from six different cohorts in which CSF was collected under standardized protocols, centrifugation, and storage conditions. Tau and p-tau (181) concentrations were measured using commercially available in vitro diagnostic immunoassays. Concentrations of CSF Aβ1–42 and Aβ1–40 were measured by ELISA, xMAP technology, chemiluminescence immunoassay (CLIA), and mass spectrometry. Statistical analyses were calculated for parametric and non-parametric comparisons, linear regression, correlation, and odds ratios. The statistical tests were adjusted for the effects of covariates (age, in particular). Results Regardless of the analysis method used and the cohorts, a slight but significant age-independent increase in the levels of Aβ40 in CSF was observed in AD. We also found a strong positive correlation between the levels of Aβ1–40 and p-tau (181) in CSF, particularly in control patients. Conclusions These results indicate that an increase in the baseline level of amyloid peptides, which are associated with an increase in p-tau (181), may be a biological characteristic and possibly a risk factor for AD. Further studies will be needed to establish a causal link between increased baseline levels of Aβ40 and the development of the disease.
Published: 2020

32. Impact of a preoperative pharmaceutical consultation in scheduled orthopedic surgery on admission: a prospective observational study

Author: Audrey Lefauconnier, Chloé Choukroun, Hélène Richard, Philippe Cuvillon, Géraldine Leguelinel-Blache, Christophe Boisson, Amélie Renaudin, Jean-Marie Kinowski, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Unité de réanimation médicale [CHU de Carémeau, Nîmes], Institut du Cancer de Montpellier (ICM), and Salvy-Córdoba, Nathalie
Subjects: Male, medicine.medical_specialty, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, Medication history, Pharmacist, Pharmacy, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 030226 pharmacology & pharmacy, law.invention, 03 medical and health sciences, Patient Admission, 0302 clinical medicine, Randomized controlled trial, law, Medication errors, Preoperative Care, Humans, Medicine, Orthopedic Procedures, Anesthesia, Prospective Studies, Drug safety, Referral and Consultation, Aged, business.industry, lcsh:Public aspects of medicine, 030503 health policy & services, Health Policy, lcsh:RA1-1270, Middle Aged, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Clinical pharmacy, Ambulatory, Orthopedic surgery, Emergency medicine, Medication reconciliation, Female, Surgery, Observational study, Health Services Research, Pharmacy Service, Hospital, 0305 other medical science, business, Research Article
Abstract: Background Medication errors have a high prevalence in surgery and management of home medication is strongly involved in these errors. In scheduled surgery, the preoperative consultation is a privileged time to inform the patient about the management of her/his home medication before admission. This study assessed the impact of a pre-anesthesia best possible medication history (PA-BPMH) on admission. The PA-BPMH was performed by a clinical pharmacist prior to the anesthesia consultation for anesthesiologists to prescribe admission medical orders for scheduled orthopedic surgery patients. Methods This was a prospective observational study which was carried out in an orthopedic surgery department. All patients over 18 years old with an elective orthopedic surgery were eligible except ambulatory surgery patients. The pharmacist registered the PA-BPMH into the software making it available for anesthesiologists for the pre-admission medication order. Finally, a medication reconciliation was performed at admission. The main outcome was the percentage of patients with at least one unintended medication discrepancy (UMD) at admission. The nature, potential clinical impact and acceptance rate of each UMD detected were assessed. Also, the PA-BPMH process was described and patients and anesthesiologists satisfaction was evaluated. Results A total of 455 patients had a pharmaceutical consultation. Medication reconciliation was performed at admission for 360 patients. Overall, at least one UMD was observed in 13.0% of patients (n = 47). A total of 63 UMD were detected. The most common type of UMD was omission (25.4%) and incorrect drug (23.8%).Two UMD (3.2%) were evaluated as life threatening. All the UMD detected were corrected on the admission medication order. Conclusion A preoperative pharmacist-anesthesiologist teamwork seems to improve the safety of perioperative management of home medication for scheduled orthopedic surgery patients. This process needs a randomized clinical trial across a wider range of surgeries before its implementation.
Published: 2020

33. Primary antiphospholipid syndrome associated with anti-phospholipase A2 receptor antibody-positive membranous nephropathy

Author: Sophie Renaud, Pascal Reboul, Hélène Perrochia, Maxime Teisseyre, Cedric Aglae, Olivier Moranne, S. Cariou, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université de Montpellier (UM), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Male, Nephrology, Membranous nephropathy, medicine.medical_specialty, Nephrotic syndrome, 030232 urology & nephrology, Case Report, 030204 cardiovascular system & hematology, lcsh:RC870-923, Glomerulonephritis, Membranous, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Gastroenterology, Nephropathy, 03 medical and health sciences, Glomerulonephritis, 0302 clinical medicine, immune system diseases, Antiphospholipid syndrome, Internal medicine, medicine, Humans, skin and connective tissue diseases, PLA2R antibody, Lupus anticoagulant, MESH: Antiphospholipid Syndrome / complications, MESH: Humans, MESH: Middle Aged, MESH: Glomerulonephritis, Membranous / immunology, business.industry, Receptors, Phospholipase A2, MESH: Glomerulonephritis, Membranous / blood, MESH: Antibodies, Antiphospholipid / blood, Middle Aged, lcsh:Diseases of the genitourinary system. Urology, medicine.disease, MESH: Male, 3. Good health, Antibodies, Antiphospholipid, MESH: Glomerulonephritis, Membranous / pathology, MESH: Receptors, Phospholipase A2 / immunology, Rituximab, business, MESH: Antiphospholipid Syndrome / blood, medicine.drug
Abstract: Background The kidney is a major target in primary antiphospholipid syndrome. Several types of nephropathy have been reported, the most frequent being acute or chronic specific vascular nephropathies and membranous nephropathy. Case presentation A 59-year-old male presented in our unit with nephrotic syndrome. He had a history of primary antiphospholipid syndrome with lupus anticoagulant treated with vitamin K antagonist therapy. On admission, antiphospholipid (lupus anticoagulant) and anti-PLA2R antibodies were positive. Screening for secondary etiologies was negative. In the context of primary antiphospholipid syndrome treated with vitamin K antagonist therapy, we did not perform a biopsy and we treated the patient with angiotensin-converting-enzyme inhibitor. No remission was observed at 6 months with persistent anti-PLA2R antibodies while antiphospholipid antibody level became negative. Consequently, kidney biopsy was performed showing both membranous nephropathy with PLA2R in deposits on immunohistochemistry with IgG4 dominance and antiphospholipid syndrome chronic vascular nephropathy. Following that, treatment with rituximab was started with secondarily a decrease in serum PLA2R antibody levels and partial remission. Conclusion We report the first association between primary antiphospholipid syndrome and membranous nephropathy with anti-PLA2R antibodies. Our observations could suggest a causal link between primary antiphospholipid syndrome and PLA2R-related membranous nephropathy. Consequently, it would be interesting to screen for anti-PLA2R antibodies for further cases of nephrotic syndrome in patients with primary antiphospholipid syndrome and to search antiphospholipid antibodies in all membranous nephropathies.
Published: 2020

34. Successful long-term remission through tapering tocilizumab infusions: a single-center prospective study

Author: Christian Jorgensen, Pierre Le Blay, Yves-Marie Pers, Rosanna Ferreira Lopez, Ahmed Larbi, Emma Rubenstein, Thierry Vincent, Chayma Ladhari, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Saint-Eloi, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), and Michel-Avella, Amandine
Subjects: medicine.medical_specialty, lcsh:Diseases of the musculoskeletal system, Maintenance, Remission, [SDV]Life Sciences [q-bio], Tapering, Neutropenia, Single Center, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pharmacotherapy, Tocilizumab, Rheumatology, Internal medicine, medicine, Rheumatoid factor, 030212 general & internal medicine, Rheumatoid arthritis, Prospective cohort study, 030203 arthritis & rheumatology, business.industry, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], chemistry, lcsh:RC925-935, business, Adverse drug reaction, Research Article
Abstract: Background Strategic drug therapy for rheumatoid arthritis (RA) patients with prolonged remission is not well defined. According to recent guidelines, tapering biological Disease-Modifying Anti-Rheumatic Drugs (bDMARDs) may be considered. We aimed to evaluate the effectiveness of long-term maintenance of tocilizumab (TCZ) treatment after the progressive tapering of infusions. Methods We conducted an exploratory, prospective, single-center, open-label study, on RA patients with sustained remission of at least 3 months and treated with TCZ infusions every 4 weeks. The initial re-treatment interval was extended to 6 weeks for the first 3 months. Thereafter, the spacing between infusions was determined by the clinician. Successful long-term maintenance following the tapering of TCZ infusions was defined by patients still treated after two years by TCZ with a minimum dosing interval of 5 weeks. Results Thirteen patients were enrolled in the study. Eight out of thirteen were still treated by TCZ after two years. Successful long-term maintenance was possible in six patients, with four patients maintaining a re-treatment interval of 8-weeks or more. We observed 5 patients with TCZ withdrawal: one showing adverse drug reaction (neutropenia) and four with secondary failure. Patients achieving successful long-term maintenance with TCZ were significantly younger than those with secondary failure (p p Conclusions A progressive tapering of TCZ infusions may be possible for many patients. However, larger studies, including more patients, are needed to confirm this therapeutic option. Trial registration NCT02909998. Date of registration: October 2008.
Published: 2020

35. Efficacy of Ronopterin (VAS203) in Patients with Moderate and Severe Traumatic Brain Injury (NOSTRA phase III trial): study protocol of a confirmatory, placebo-controlled, randomised, double blind, multi-centre study

Author: Frank Tegtmeier, Reinhard Schinzel, Ronny Beer, Diederik Bulters, Jean-Yves LeFrant, Joan Sahuquillo, Andreas Unterberg, Peter Andrews, Antonio Belli, Javier Ibanez, Alfonso Lagares, Michael Mokry, Harald Willschke, Charlotte Flüh, Erich Schmutzhard, on behalf of the NOSTRA Investigators, Vasopharm GmbH (IGZ Würzburg), Innsbruck Medical University [Austria] (IMU), Wessex Neurological Centre, Southampton General Hospital, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Vall d'Hebron University Hospital [Barcelona], UniversitätsKlinikum Heidelberg, Western General Hospital, Edinburgh, Queens Elizabeth Hospital [Birmingham], Hospital Universitario Son Espases, Hospital Universitario 12 de Octubre [Madrid], University Hospital Graz, Medizinische Universität Wien = Medical University of Vienna, University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), and Kiel University
Subjects: humanos, adolescente, Medicine (miscellaneous), MESH: Biopterin, Placebos, Study Protocol, Traumatic brain injury, 0302 clinical medicine, estudios prospectivos, MESH: Double-Blind Method, Pharmacology (medical), Prospective Studies, 030212 general & internal medicine, mediana edad, MESH: Treatment Outcome, Outcome, lcsh:R5-920, MESH: Middle Aged, resultado del tratamiento, Middle Aged, adulto, MESH: Case-Control Studies, 3. Good health, adulto joven, Treatment Outcome, MESH: Young Adult, MESH: Nitric Oxide Synthase, lcsh:Medicine (General), escala del coma de Glasgow, óxido nítrico sintasa, Adult, Adolescent, estudios de casos y controles, traumatismos cerebrales, MESH: Placebos, MESH: Brain Injuries, Traumatic, Randomised controlled trials, Young Adult, 03 medical and health sciences, Double-Blind Method, MESH: Glasgow Coma Scale, Humans, Glasgow Coma Scale, método con doble ocultación, MESH: Infusions, Intravenous, MESH: Adolescent, MESH: Humans, [SCCO.NEUR]Cognitive science/Neuroscience, Nitric oxide synthase inhibition, MESH: Quality of Life, MESH: Adult, Biopterin, MESH: Prospective Studies, biopterina, Brain Injuries, Case-Control Studies, calidad de vida, Quality of Life, MESH: Europe, Nitric Oxide Synthase, 030217 neurology & neurosurgery
Abstract: Background Traumatic brain injury is a leading cause of death and disability worldwide. The nitric oxide synthase inhibitor Ronopterin was shown to improve clinical outcome by enhancing neuroprotection in a phase IIa trial. Methods/design The NOSTRA phase III trial (Ronopterin in traumatic brain injury) is a multi-centre, prospective, randomised, double-blinded, placebo-controlled, phase III trial in Europe. It aims at determining whether the administration of Ronopterin compared to placebo improves neurological outcome in patients with moderate or severe traumatic brain injury at 6 months after injury. The trial is designed to recruit patients between 18 and 60 years of age with moderate or severe traumatic brain injury (Glasgow Coma Scale score >= 3) and requiring insertion of an intracranial pressure probe. Trial patients will receive a 48-h intravenous infusion of either Ronopterin or placebo starting at the earliest 6 h and at the latest 18 h after injury. The primary outcome will be the extended Glasgow Outcome Score (eGOS) at 6 months. Secondary outcomes will include the Quality of Life Index (QOLIBRI) at 6 months after the injury and the eGOS at 3 months after the injury. Additionally, effects on mortality, intracranial pressure and cerebral perfusion pressure are evaluated. Discussion The trial aims to provide evidence on the efficacy and safety of Ronopterin in patients with traumatic brain injury., The study is completely funded by vasopharm GmbH. FT and RS as employees of vasopharm were involved in the design of the study.
Published: 2020

36. Mortality, complication, and fusion rates of patients with odontoid fracture: the impact of age and comorbidities in 204 cases

Author: Maxime Lleu, Yann Philippe Charles, Nicolas Lonjon, Benjamin Blondel, Stéphane Fuentes, Cédric Barrey, Joel Godard, Yves Ntilikina, Paulo Marinho, Eurico Freitas, Nicolas Bronsard, Julien Berthiller, Pascal Kouyoumdjian, Jeremy Allia, Vincent Challier, Benjamin Nicot, CHU Strasbourg, Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Pasteur [Nice] (CHU), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Biomécanique des Interactions et de l'Organisation des Tissus et des Cellules (BIOTIC), Laboratoire de Mécanique et Génie Civil (LMGC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service de Neurochirurgie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Gui de Chauliac [Montpellier], Mécanismes moléculaires dans les démences neurodégénératives (MMDN), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Pôle Information Médicale Evaluation Recherche (IMER), Hospices Civils de Lyon (HCL), and Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL]
Subjects: medicine.medical_specialty, Epidemiology, Comorbidity, Odontoid fracture, Conservative Treatment, Fracture Fixation, Internal, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Odontoid Process, Humans, Medicine, Orthopedics and Sports Medicine, Prospective Studies, Mortality, Fusion, Fracture type, Aged, 030222 orthopedics, business.industry, Mortality rate, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], 030229 sport sciences, General Medicine, Middle Aged, medicine.disease, 3. Good health, Surgery, Conservative treatment, Pseudarthrosis, Spinal Fusion, Orthopedic surgery, Spinal Fractures, Morbidity, business, Complication, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; PurposeThe French Society of Spine Surgery (SFCR) conducted a prospective epidemiologic multicenter study. The purpose was to investigate mortality, complication, and fusion rates in patients with odontoid fracture, depending on age, comorbidities, fracture type, and treatment.MethodsOut of 204 patients, 60 were ≤ 70 years and 144 were > 70 years. Demographic data, comorbidities, treatment types and complications (general medical, infectious, neurologic, and mechanical), and death were registered within the first year. Fractures were classified according to Anderson–D’Alonzo and Roy–Camille on the initial CT. A 1-year follow-up CT was available in 144 patients to evaluate fracture consolidation.ResultsType II and oblique-posterior fractures were the most frequent patterns. The treatment was conservative in 52.5% and surgical in 47.5%. The mortality rate in patients ≤ 70 was 3.3% and 16.7% in patients > 70 years (p = 0.0002). Fracture pattern and treatment type did not influence mortality. General medical complications were significantly more frequent > 70 years (p = 0.021) and after surgical treatment (p = 0.028). Neurologic complications occurred in 0.5%, postoperative infections in 2.0%, and implant-related mechanical complications in 10.3% (associated with pseudarthrosis). Fracture fusion was observed in 93.5% of patients ≤ 70 years and in 62.5% >70 years (p
Published: 2018

37. Patient dose reference levels in surgery: a multicenter study

Author: Cécile Etard, Jean Paul Beregi, Ahmed Larbi, P. Branchereau, O. Mares, D. Defez, Rémy Coulomb, Joël Greffier, Fabricio Pereira, C. Duverger, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), and Université Montpellier 1 (UM1)-Université de Montpellier (UM)
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Shoulder surgery, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Radiation Dosage, Radiography, Interventional, 030218 nuclear medicine & medical imaging, law.invention, Intramedullary rod, Young Adult, 03 medical and health sciences, Radiation Protection, 0302 clinical medicine, Reference Values, law, Humans, Medicine, Fluoroscopy, media_common.cataloged_instance, Radiology, Nuclear Medicine and imaging, European union, Radiometry, Aged, Retrospective Studies, media_common, medicine.diagnostic_test, business.industry, Interventional radiology, General Medicine, Middle Aged, 3. Good health, Surgery, medicine.anatomical_structure, Quartile, Surgical Procedures, Operative, 030220 oncology & carcinogenesis, Orthopedic surgery, Female, France, Radiology, Ankle, business
Abstract: International audience; Objective To assess diagnostic reference levels (DRLs) in surgery for the most frequent procedures as required by the European Directive 2013/59/Euratom. Methods A survey was conducted in six centers. Eight orthopedic, urology and gastrointestinal surgical procedures were analyzed. Kerma area product (KAP) and fluoroscopy time (FT) were recorded for 50 patients (except for elbow 30 patients) per procedure and per center from September 2016 to September 2017. DRLs were calculated as the 3rd quartiles of the distributions. For shoulder surgery, DRLs were defined according to the complexity of the procedure. For hand/wrist and foot/ankle surgery, DRLs were defined according to the technology (conventional C-arm vs. mini-C-arm). Results Results of 1870 procedures were retrieved. DRLs were calculated for the two dosimetric indicators and the eight procedures. DRLs were 2130 mGy.cm2 and 1.4 min for proximal femoral intramedullary nail, 1185 mGy.cm2 and 0.9 min for laparoscopic cholecystectomy and 2195 mGy.cm2 and 1.0 min for double-J (pigtail) ureteral catheter insertion. For shoulder surgery, KAP and FT were significantly higher (p andlt; 0.05) for intramedullary procedures compared to extramedullary procedures. For hand/wrist and foot/ankle surgery, the KAPs were significantly higher (p andlt; 0.05) with conventional C-arm compared to mini-C-arm, but FTs were not significantly different (p not significant). Conclusion This study reports DRLs in surgery based on a multicentric survey. Key Points • Delivered dose in surgery depends on procedure, practice and patient. • Diagnostic reference levels (DRLs) are proposed for eight surgical procedures. • DRLs are useful to benchmark practices and optimize protocols. © 2018, European Society of Radiology.
Published: 2018

38. Validity and internal consistency of the French version of the revised Skin Management Needs Assessment Checklist in people with spinal cord injury

Author: Gélis, Anthony, Dupeyron, Arnaud, Daures, Jean Pierre, Goossens, David, Gault, Dominique, Pedelucq, Jean Paul, Enjalbert, Michel, Maupas, Eric, Kennedy, Paul, Fattal, Charles, Group, French SMNAC, Centre Mutualiste de Réeducation Neurologique Propara (PROPARA), Languedoc Mutualité, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université de Montpellier (UM), Euromov (EuroMov), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre de Rééducation Fonctionnelle Divio [Dijon] (CRF COS Divio)
Subjects: Adult, Male, Health Knowledge, Attitudes, Practice, 030506 rehabilitation, medicine.medical_specialty, Psychometrics, Cross-sectional study, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Hospital Anxiety and Depression Scale, Skin Diseases, Young Adult, 03 medical and health sciences, 0302 clinical medicine, 80 and over, medicine, Humans, Spinal cord injury, Spinal Cord Injuries, Aged, Rank correlation, Aged, 80 and over, Practice, Rehabilitation, business.industry, Health Knowledge, Self-Management, Reproducibility of Results, Construct validity, General Medicine, Middle Aged, medicine.disease, Checklist, 3. Good health, Cross-Sectional Studies, Neurology, Attitudes, Physical therapy, Female, Neurology (clinical), 0305 other medical science, business, Needs Assessment, 030217 neurology & neurosurgery
Abstract: International audience; STUDY DESIGN: Cross-sectional psychometrics study. OBJECTIVES: To determine the construct validity and internal consistency of the revised Skin Management Needs Assessment Checklist (revised SMnac). SETTING: Six spinal cord rehabilitation centers. METHODS: One-hundred and thirty-two community-dwelling individuals with spinal cord injury (SCI) were included. Construct validity was assessed by a Spearman's rank correlation coefficient between the revised SMnac and several questionnaires: Rosenberg Self-Esteem Scale, Ways of Coping Questionnaire, Hospital Anxiety and Depression Scale (HADS), Braden scale; or clinical variables: educational level, presence of a pressure ulcer (PU), history of multiple PUs, time since injury, and pain. RESULTS: The study evidenced construct validity with a fair to moderate correlation coefficient between the revised SMnac and Rosenberg scale (rs = 0.25; p = 0.03), active coping (rs = 0.29; p = 0.001), HADS (rs = -0.43; p \textless 0.0001), and time since injury (rs = 0.49; p \textless 0.0001). The presence of PU and history of multiple PUs were strongly correlated with the revised SMnac score (respectively, p = 0.01 and 0.001). Internal consistency was excellent (α = 0.907). CONCLUSION: These results show that the revised SMnac is a valid tool to assess PU self-management in individuals with SCI. Further studies are needed to assess the revised SMnac's responsiveness to change.
Published: 2018

39. Robotic versus laparoscopic distal pancreatectomy: a French prospective single-center experience and cost-effectiveness analysis

Author: Gregoire Mercier, John Chauvat, Guillaume Bourel, Jean-Michel Fabre, F. Guillon, Astrid Herrero, Isabelle Pirlet, Regis Souche, Frédéric Borie, David Nocca, Service Médico-Chirurgical des Maladies de l'Appareil Digestif et de Transplantation Hépatique, CHU Saint-Eloi, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre d'Etudes Politiques de l'Europe Latine (CEPEL), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, medicine.medical_specialty, Cost-Benefit Analysis, Left pancreatectomy, Pancreatic surgery, Operative Time, Distal pancreatectomy, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030230 surgery, Single Center, 03 medical and health sciences, Pancreatectomy, 0302 clinical medicine, Robotic Surgical Procedures, Internal medicine, medicine, Robot-assisted surgery, Humans, Robotic surgery, Prospective Studies, Hospital Costs, Prospective cohort study, Laparoscopy, Aged, Aged, 80 and over, medicine.diagnostic_test, business.industry, Pancreatic Diseases, Perioperative, Length of Stay, Middle Aged, Hepatology, medicine.disease, Costs, 3. Good health, Surgery, Treatment Outcome, Pancreatic fistula, 030220 oncology & carcinogenesis, Female, France, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Abdominal surgery
Abstract: International audience; BACKGROUND:Benefits and cost-effectiveness of robotic approach for distal pancreatectomy (DP) remain debated. In this prospective study, we aim to compare the short-term results and real costs of robotic (RDP) and laparoscopic distal pancreatectomy (LDP).METHODS:From 2011 until 2016, all consecutive patients underwent minimally invasive DP were included and data were prospectively collected. Patients were assigned in two groups, RDP and LDP, according to the availability of the Da Vinci® Surgical System for our Surgical Unit.RESULTS:A minimally invasive DP was performed in 38 patients with a median age of 61 years old (44-83 years old) and a BMI of 26 kg/m2 (20-31 kg/m2). RDP group (n = 15) and LDP group (n = 23) were comparable concerning demographic data, BMI, ASA score, comorbidities, malignant lesions, lesion size, and indication of spleen preservation. Median operative time was longer in RDP (207 min) compared to LDP (187 min) (p = 0.047). Conversion rate, spleen preservation failure, and perioperative transfusion rates were nil in both groups. Pancreatic fistula was diagnosed in 40 and 43% (p = 0.832) of patients and was grade A in 83 and 80% (p = 1.000) in RDP and LDP groups, respectively. Median postoperative hospital stay was similar in both groups (RDP: 8 days vs. LDP: 9 days, p = 0.310). Major complication occurred in 7% in RDP group and 13% in LDP group (p = 1.000). Ninety-days mortality was nil in both groups. No difference was found concerning R0 resection rate and median number of retrieved lymph nodes. Total cost of RDP was higher than LDP (13611 vs. 12509 €, p
Published: 2018

40. Occupational exposure to pesticides: development of a job-exposure matrix for use in population-based studies (PESTIPOP)

Author: Pierre Lebailly, Camille Carles, Pascale Fabbro-Peray, Lucile Migault, Clément Piel, Séverine Tual, Camille Pouchieu, Yolande Esquirol, Ghislaine Bouvier, Isabelle Baldi, Cancer environnement (EPICENE ), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], CHU Toulouse [Toulouse], Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, BESPIM, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, Epidemiology, Population, Job-exposure matrix, 030501 epidemiology, Toxicology, Risk Assessment, Occupational safety and health, 03 medical and health sciences, 0302 clinical medicine, Occupational Exposure, Surveys and Questionnaires, Environmental health, Humans, Occupations, Pesticides, education, Reliability (statistics), education.field_of_study, business.industry, Public Health, Environmental and Occupational Health, Reproducibility of Results, Middle Aged, Pesticide, 030210 environmental & occupational health, Pollution, Geography, Agriculture, Case-Control Studies, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Female, France, Metric (unit), Epidemiologic Methods, 0305 other medical science, Risk assessment, business, Environmental Monitoring
Abstract: International audience; Occupational exposure to pesticides concerns a wide population of workers not only in agriculture. The reliability of self-reported information on pesticide use is questionable because of the diversity of use. The PESTIPOP job-exposure matrix has been designed to assess pesticide occupational exposure in the general population. The matrix is composed of two axes: the first axis corresponding to jobs (combinations of occupations and industries) and the second one to pesticide exposure. The estimated exposure metric is the probability of exposure coupled with a reliability assessment (low, medium or high). These metrics were defined by combining different sources: (1) an a priori expert assessment (Agricultural industry experts); (2) data from a multicenter case-control study on brain tumors in the general population (occupational history, specific questionnaires); and (3) an a posteriori expert assessment based on the data of a case-control study. So far, 2559 jobs have been identified and 209 (8%) were found to be exposed to pesticides. Jobs with agricultural exposure had a higher exposure probability than jobs with non-agricultural exposure (wood preservation, park maintenance, pest control). Indirect exposure was more frequent than direct exposure. The PESTIPOP matrix will be transcoded into international classifications for use in epidemiological studies.
Published: 2017

41. OXA-48-like carbapenemases producing Enterobacteriaceae in different niches

Author: Assia Mairi, Aziz Touati, Jean-Philippe Lavigne, Albert Sotto, Alix Pantel, Virulence bactérienne et maladies infectieuses (VBMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire d'écologie microbienne, Université Abderrahmane Mira [Béjaïa], and Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)
Subjects: 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Livestock, 030106 microbiology, Animals, Wild, Environment, Biology, Communicable Diseases, Emerging, Microbiology, beta-Lactamases, Carbapenemase, Niches, Persistence, 03 medical and health sciences, Medical microbiology, Bacterial Proteins, Enterobacteriaceae, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Environmental Microbiology, polycyclic compounds, medicine, Animals, Humans, 2. Zero hunger, Ecological niche, Genetics, Cross Infection, business.industry, Enterobacteriaceae Infections, Outbreak, General Medicine, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, 3. Good health, Carbapenem-Resistant Enterobacteriaceae, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, bacteria, Mediterranean area, business, OXA-48-like
Abstract: International audience; The emergence of carbapenem-resistant enterobacterial species poses a serious threat to public health worldwide. OXA-48-type carbapenem-hydrolyzing class D β-lactamases are widely distributed among Enterobacteriaceae, with significant geographical differences. To date, 11 OXA-48-like variants have been identified, with classical OXA-48 being the most widespread. These enzymes show high-level hydrolytic activity against penicillins and low-level hydrolysis towards carbapenems. Since the first description of the OXA-48 carbapenemase in Turkey, bacterial strains producing the enzyme have been extensively reported in nosocomial and community outbreaks in many parts of the word, particularly in the Mediterranean area and European countries. The rapid spread of Enterobacteriaceae producing OXA-48-like enzymes in different ecosystems has become a serious issue recently. The number of reservoirs for such organisms is increasing, not only in hospitals, but also in the community, among animals (e.g., livestock, companion animals, and wildlife) and in the environment. This review aims to summarize the main characteristics of the OXA-48-type carbapenemases, covering genetic and enzymatic traits, their epidemiology, clonality and associated genes, correlation with extended-spectrum β-lactamases (ESBLs) or plasmidic AmpC (pAmpC) in different bacterial species worldwide.
Published: 2017

42. Lung real time three-dimensional imaging in critically ill ventilated patients: a global diagnosis concordance study

Author: Claire Roger, Xavier Bobbia, Jean-Yves Lefrant, Benjamin Louart, Aurélien Daurat, Laurent Muller, Jean-Marc Le Goff, Pierre Géraud Claret, Stéphanie Bulyez, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and CHU Clermont-Ferrand
Subjects: Male, Pleural effusion, 3-Dimensional ultrasonography, Pilot Projects, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Single Center, law.invention, 0302 clinical medicine, law, Diagnosis, Computer-Assisted, Prospective Studies, Medical diagnosis, Lung, ComputingMilieux_MISCELLANEOUS, Ultrasonography, Observer Variation, Lung ultrasound, Middle Aged, Intensive care unit, 3. Good health, Intensive Care Units, medicine.anatomical_structure, Female, Radiology, Algorithms, Adult, medicine.medical_specialty, Critical Care, Critical Illness, Point-of-Care Systems, Concordance, Health Informatics, 03 medical and health sciences, Imaging, Three-Dimensional, Computer Systems, medicine, Humans, Aged, Pilot study, Critically ill, business.industry, LUS, Reproducibility of Results, 030208 emergency & critical care medicine, medicine.disease, Confidence interval, Surgery, Anesthesiology and Pain Medicine, ICU, business, Software, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Lung ultrasound (LUS) increases clinical diagnosis performance in intensive care unit (ICU). Real-time three-dimensional (3-D) imaging was compared with two-dimensional (2-D) LUS by assessing the global diagnosis concordance. In this single center, prospective, observational, pilot study, one trained operator performed a 3-D LUS immediately after a 2-D LUS in eight areas of interest on the same areas in 16 ventilated critically ill patients. All cine loops were recorded on a computer without visible link between 2-D and 3-D exams. Two experts blindly reviewed cine loops. Four main diagnoses were proposed: normal lung, consolidation, pleural effusion and interstitial syndrome. Fleiss κ and Cohen's κ values were calculated. In 252 LUS cine loops, the concordance between 2-D and 3-D exams was 83.3% (105/126), 77.6% (99/126) and 80.2% (101/126) for the trained operator and the experts respectively. The Cohen's κ coefficient value was 0.69 [95% Confidence Interval (CI) 0.58-0.80] for expert 1 meaning a substantial agreement. The inter-rater reliability was very good (Fleiss' κ value = 0.94 [95% CI 0.87-1.0]) for 3-D exams. The Cohen's κ was excellent for pleural effusion (κ= 0.93 [95% CI 0.76-1.0]), substantial for normal lung diagnosis (κ = 0.68 [95% CI 0.51-0.86]) and interstitial syndrome (κ = 0.62 [95% CI 0.45-0.80]) and fair for consolidation diagnoses (κ = 0.47 [95% CI 0.30-0.64]). In ICU ventilated patients, there was a substantial concordance between 2-D and 3-D LUS with a good inter-rater reliability. However, the diagnosis concordance for lung consolidation is poor.
Published: 2017

43. Evaluation of Changes in Sexual Function Related to Uterine Fibroid Embolization (UFE): Results of the EFUZEN Study

Author: Kovacsik, Hélène Vernhet, Herbreteau, Denis, Bommart, Sébastien, Beregi, Jean-Paul, Bartoli, Jean-Michel, Sapoval, Marc, Research Group, French society of interventional and cardiovascular imaging (SFICV), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Assistance Publique - Hôpitaux de Marseille (APHM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Adult, Quality of life, medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Imaging data, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Gynecology, 030219 obstetrics & reproductive medicine, Leiomyoma, business.industry, Uterus, Uterine fibroid embolization, Embolization, Therapeutic, Magnetic Resonance Imaging, 3. Good health, Sexual Dysfunction, Physiological, Female sexual function, Uterine Neoplasms, Female, Observational study, Cardiology and Cardiovascular Medicine, Sexual function, business, Uterine arteries, Follow-Up Studies
Abstract: The main goal of the study was to evaluate sexual function before and one year after UFE. The secondary goals were to evaluate the quality of life before and one year after UFE and to determine the relation of imaging findings (MRI data) before and 3–6 months after UFE to changes in sexual function and quality of life. Study design: a prospective, multicenter (25 centers) observational study was conducted. Patients: a total of 264 consecutive symptomatic women undergoing UFE using Embozene® (Celonova) from March 2012 to May 2013 were enrolled. Clinical data: the sexual function score and the quality of life score were calculated using the previously validated Female Sexual Function Index (FSFI) by Rosen and UFS-QOL by Spies, respectively, before and one year after UFE. Imaging data: MRI were performed before and 3–6 months after UFE. Data recorded were uterine and main fibroid volume, percentage of fibroid enhancement after injection of gadolinium. Impact of imaging data before and after UFE FSFS scores and QOL scores after UFE was searched. Complete FSFI study and QOL study were obtained in 170 and 192 women, respectively. At 1 year post-UFE, improvement of FSFI score was seen in 134/170 women (78.8%), QOL scores were improved in 183/203 women (90.2%) and symptoms severity in 163/192 (84.9%). The relation between main fibroid reduction, decrease of fibroid enhancement and global UFS-QOL and FSFI scores was not established. At one year post-embolization, UFE significantly improves all aspects of sexual function and quality of life.
Published: 2017

44. Reversible 'ears of the lynx' sign in Marchiafava–Bignami disease

Author: Jean-Marc Le Goff, Dimitri Renard, Eric Thouvenot, Jean-Sebastien Guillamo, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Génomique Fonctionnelle (IGF), and 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)
Subjects: Male, Pathology, medicine.medical_specialty, Neurology, business.industry, [SDV]Life Sciences [q-bio], Remission Induction, General Medicine, Marchiafava–Bignami disease, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Corpus Callosum, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Vasogenic edema, 0302 clinical medicine, Vitamin B Complex, medicine, Humans, Neurology (clinical), business, Marchiafava-Bignami Disease, 030217 neurology & neurosurgery, Neuroradiology
Published: 2018

45. Combining mobile-health (mHealth) and artificial intelligence (AI) methods to avoid suicide attempts: the Smartcrises study protocol

Author: Sofian Berrouiguet, Antonio Artés-Rodríguez, Philippe Courtet, María Luisa Barrigón, Enrique Baca-García, Jorge Lopez Castroman, Département Logique des Usages, Sciences sociales et Sciences de l'Information (IMT Atlantique - LUSSI), IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), CHRU Brest - Psychiatrie Adulte (CHU - Brest- Psychiatrie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Soins Primaires, Santé Publique, Registre des cancers de Bretagne Occidentale (SPURBO), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hospital General Universitario 'Gregorio Marañón' [Madrid], Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Department of Psychiatry (Hospital Universitario Fundacion Jimenez Diaz ), UAM. Departamento de Psiquiatría, Salvy-Córdoba, Nathalie, IMT Atlantique (IMT Atlantique), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Institut Brestois Santé Agro Matière (IBSAM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Comunidad de Madrid, and Ministerio de Economía y Competitividad (España)
Subjects: Male, Computer science, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Appetite, Wearable computer, Suicide, Attempted, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], [SCCO]Cognitive science, Study Protocol, 0302 clinical medicine, lcsh:Psychiatry, Surveys and Questionnaires, 030212 general & internal medicine, mHealth, Wearable technology, Randomized Controlled Trials as Topic, Telecomunicaciones, Telemedicine, 3. Good health, Suicide, Psychiatry and Mental health, Identification (information), Research Design, Female, France, Smartphone, [INFO.INFO-AI] Computer Science [cs]/Artificial Intelligence [cs.AI], Adult, lcsh:RC435-571, Medicina, Ecological Momentary Assessment, Polysomnography, Automatic identification and data capture, Data security, Wearable Electronic Devices, 03 medical and health sciences, Artificial Intelligence, Humans, Data mining, Sensors, Wearables, business.industry, [SCCO] Cognitive science, 030227 psychiatry, Spain, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Digital footprint, Observational study, Artificial intelligence, business
Abstract: The screening of digital footprint for clinical purposes relies on the capacity of wearable technologies to collect data and extract relevant information’s for patient management. Artificial intelligence (AI) techniques allow processing of real-time observational information and continuously learning from data to build understanding. We designed a system able to get clinical sense from digital footprints based on the smartphone’s native sensors and advanced machine learning and signal processing techniques in order to identify suicide risk. Method/design: The Smartcrisis study is a cross-national comparative study. The study goal is to determine the relationship between suicide risk and changes in sleep quality and disturbed appetite. Outpatients from the Hospital Fundación Jiménez Díaz Psychiatry Department (Madrid, Spain) and the University Hospital of Nimes (France) will be proposed to participate to the study. Two smartphone applications and a wearable armband will be used to capture the data. In the intervention group, a smartphone application (MEmind) will allow for the ecological momentary assessment (EMA) data capture related with sleep, appetite and suicide ideations. Discussion: Some concerns regarding data security might be raised. Our system complies with the highest level of security regarding patients’ data. Several important ethical considerations related to EMA method must also be considered. EMA methods entails a non-negligible time commitment on behalf of the participants. EMA rely on daily, or sometimes more frequent, Smartphone notifications. Furthermore, recording participants’ daily experiences in a continuous manner is an integral part of EMA. This approach may be significantly more than asking a participant to complete a retrospective questionnaire but also more accurate in terms of symptoms monitoring. Overall, we believe that Smartcrises could participate to a paradigm shift from the traditional identification of risks factors to personalized prevention strategies tailored to characteristics for each patient, This study was partly funded by Fundación Jiménez Díaz Hospital, Instituto de Salud Carlos III (PI16/01852), Delegación del Gobierno para el Plan Nacional de Drogas (20151073), American Foundation for Suicide Prevention (AFSP) (LSRG-1-005-16), the Madrid Regional Government (B2017/BMD-3740 AGES-CM 2CM; Y2018/TCS-4705 PRACTICO-CM) and Structural Funds of the European Union. MINECO/FEDER (‘ADVENTURE’, id. TEC2015–69868-C2–1-R) and MCIU Explora Grant ‘aMBITION’ (id. TEC2017–92552-EXP), the French Embassy in Madrid, Spain, The foundation de l’avenir, and the Fondation de France. The work of D. Ramírez and A. Artés-Rodríguez has been partly supported by Ministerio de Economía of Spain under projects: OTOSIS (TEC2013–41718-R), AID (TEC2014–62194-EXP) and the COMONSENS Network (TEC2015–69648-REDC), by the Ministerio de Economía of Spain jointly with the European Commission (ERDF) under projects ADVENTURE (TEC2015– 69868-C2–1-R) and CAIMAN (TEC2017–86921-C2–2-R), and by the Comunidad de Madrid under project CASI-CAM-CM (S2013/ICE-2845). The work of P. Moreno-Muñoz has been supported by FPI grant BES-2016-077626
Published: 2019

46. Persistent response to vemurafenib in metastatic ameloblastoma with BRAF mutation: a case report

Author: Marie Karanian, Antoine Arnaud, Celine Mahier Ait Oukhatar, Alexandre Evrard, Morgane Broudic-Guibert, Rania Boustany-Grenier, Jean-Yves Blay, Léa Vazquez, N. Hoog-Labouret, Sophie Taïeb, Institut Sainte Catherine [Avignon], Centre Léon Bérard [Lyon], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Division de la recherche et de l'innovation [Boulogne Billancourt] (INCa), Institut national du cancer [Boulogne] (INCA), UNICANCER [Paris], Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), and Université de Lille-UNICANCER
Subjects: Adult, Proto-Oncogene Proteins B-raf, Oncology, medicine.medical_specialty, Oral treatment, Lung Neoplasms, medicine.medical_treatment, Locally advanced, lcsh:Medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030204 cardiovascular system & hematology, medicine.disease_cause, BRAF, Targeted therapy, Ameloblastoma, 03 medical and health sciences, 0302 clinical medicine, Surgical oncology, Internal medicine, Case report, medicine, Humans, Vemurafenib, Protein Kinase Inhibitors, Mutation, MESH: Lung Neoplasms / drug therapy, Lung Neoplasms / secondary, Lung Neoplasms / pahology, Protein Kinase Inhibitors / administration & dosage, business.industry, lcsh:R, General Medicine, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, Jaw Neoplasms, 3. Good health, Clinical trial, 030220 oncology & carcinogenesis, Metastatic, Female, business, medicine.drug
Abstract: International audience; Ameloblastomas are uncommon locally aggressive tumors of odontogenic epithelium that rarely metastasize. Currently, there is no standard of care for the metastatic forms. Several studies have shown that ameloblastomas frequently have a BRAF mutation.Case presentation: We report a case of a 33-year-old Caucasian woman with ameloblastoma diagnosed 30 years ago who developed lung metastasis 19 years ago. Systemic oral treatment with vemurafenib, a BRAF inhibitor, was initiated 28 months ago within the AcSé French basket clinical trial of vemurafenib.Conclusions: The patient has shown a durable clinical, functional, and radiographic partial response with vemurafenib. These observations suggest the possibility of introducing neoadjuvant and/or adjuvant targeted therapy in locally advanced ameloblastoma to improve outcome. BRAF inhibition has proved to be an efficient strategy in patients with a BRAF-mutated ameloblastoma.
Published: 2019

47. Evaluation of treatment response in adults with relapsing MOG-Ab-associated disease

Author: Françoise Durand-Dubief, Sandra Vukusic, Jérôme De Seze, Damien Biotti, Caroline Papeix, Elisabeth Maillart, Romain Deschamps, Nuria Sola-Valls, Pierre Labauge, Jonathan Ciron, Bertrand Bourre, Alvaro Cobo-Calvo, Romain Marignier, Mikael Cohen, Alexis Montcuquet, Bertrand Audoin, Maria Sepúlveda, Hélène Zéphir, Anne Ruiz, Albert Saiz, Xavier Ayrignac, Eric Thouvenot, Sara Llufriu, Nicolas Collongues, Fabien Rollot, Yolanda Blanco, Thaís Armangue, Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Hospices Civils de Lyon, Departement de Neurologie (HCL), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (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), University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Université de Lyon, Observatoire Français de la Sclérose En Plaques [Lyon] (OFSEP), Hospital Sant Joan de Déu [Barcelona], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Aix Marseille Université (AMU), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), RMN et optique : De la mesure au biomarqueur, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), 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)-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)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Hôpital Pasteur [Nice] (CHU), Centre Hospitalier Universitaire de Nice (CHU Nice), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Centre de recherche en neurosciences de Lyon (CRNL), 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), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Pierre-Paul Riquet [Toulouse], CHU Toulouse [Toulouse], Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université 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), Gestionnaire, Hal Sorbonne Université, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), and Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL)
Subjects: Male, 0301 basic medicine, Propensity score, Esclerosi múltiple, Azathioprine, Treatment response, lcsh:RC346-429, Cohort Studies, 0302 clinical medicine, Maintenance therapy, Medicine, 10. No inequality, General Neuroscience, Middle Aged, Neuromyelitis optica, 3. Good health, Treatment Outcome, Neurology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Rituximab, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Cyclophosphamide, Immunology, Immunoglobulins, Therapeutics, MOG antibodies, Lower risk, Multiple sclerosis, Young Adult, 03 medical and health sciences, Cellular and Molecular Neuroscience, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], lcsh:Neurology. Diseases of the nervous system, Survival analysis, Aged, Autoantibodies, Retrospective Studies, Expanded Disability Status Scale, business.industry, Research, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Terapèutica, medicine.disease, 030104 developmental biology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Myelin-Oligodendrocyte Glycoprotein, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Immunoglobulines, business, 030217 neurology & neurosurgery
Abstract: Background Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are related to several acquired demyelinating syndromes in adults, but the therapeutic approach is currently unclear. We aimed to describe the response to different therapeutic strategies in adult patients with relapsing MOG-Ab-associated disease. Methods This is a retrospective study conducted in France and Spain including 125 relapsing MOG-Ab patients aged ≥ 18 years. First, we performed a survival analysis to investigate the relapse risk between treated and non-treated patients, performing a propensity score method based on the inverse probability of treatment weighting. Second, we assessed the annualised relapse rates (ARR), Expanded Disability Status Scale (EDSS) and visual acuity pre-treatment and on/end-treatment. Results Median age at onset was 34.1 years (range 18.0–67.1), the female to male ratio was 1.2:1, and 96% were Caucasian. At 5 years, 84% (95% confidence interval [CI], 77.1–89.8) patients relapsed. At the last follow-up, 66 (52.8%) received maintenance therapy. Patients initiating immunosuppressants (azathioprine, mycophenolate mophetil [MMF], rituximab) were at lower risk of new relapse in comparison to non-treated patients (HR, 0.41; 95CI%, 0.20–0.82; p = 0.011). Mean ARR (standard deviation) was reduced from 1.05(1.20) to 0.43(0.79) with azathioprine (n = 11; p = 0.041), from 1.20(1.11) to 0.23(0.60) with MMF (n = 11; p = 0.033), and from 1.08(0.98) to 0.43(0.89) with rituximab (n = 26; p = 0.012). Other immunosuppressants (methotrexate/mitoxantrone/cyclophosphamide; n = 5), or multiple sclerosis disease-modifying drugs (MS-DMD; n = 9), were not associated with significantly reduced ARR. Higher rates of freedom of EDSS progression were observed with azathioprine, MMF or rituximab. Conclusion In adults with relapsing MOG-Ab-associated disease, immunosuppressant therapy (azathioprine, MMF and rituximab) is associated with reduced risk of relapse and better disability outcomes. Such an effect was not found in the few patients treated with MS-DMD. Electronic supplementary material The online version of this article (10.1186/s12974-019-1525-1) contains supplementary material, which is available to authorized users.
Published: 2019

48. Author Correction: A framework to identify contributing genes in patients with Phelan-McDermid syndrome

Author: Stephan Kemeny, Sandrine Passemard, Sandra Chantot-Bastaraud, Chloé Quélin, Laurence Perrin, Julien Buratti, Patrick Edery, Céline Dupont, Chantal Missirian, Philippe Vago, Alexandra Afenjar, Marie-Laure Vuillaume, Yline Capri, Klaus Dieterich, Laila El Khattabi, Charles Coutton, Françoise Devillard, Annick Toutain, Alain Verloes, Nicole Philip, Hubert Journel, Véronique Satre, Marie Ducloy, Delphine Héron, Richard Delorme, Cédric Le Caignec, Anne-Claude Tabet, Damien Sanlaville, Isabelle Marey, Laurence Faivre, Christèle Dubourg, Anne-Laure Mosca-Boidron, Laetitia Gouas, Abdelamdjid Benmansour, Jean Chiesa, Séverine Drunat, Cyril Mignot, Aurélia Jacquette, Boris Keren, Claire S. Leblond, Claire Beneteau, Brigitte Benzacken, Vincent Gatinois, Olivier Pichon, Damien Haye, Roberto Toro, Sandra Whalen, Dominique Martin, Thomas Rolland, Thomas Bourgeron, Albert David, Alexandre Mathieu, Mélanie Fradin, Frédérique Amsellem, Bertrand Isidor, James Lespinasse, Caroline Rooryck, Jacques Puechberty, Eva Pipiras, Lucile Pinson, Didier Lacombe, Jonathan M. Levy, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Département de génétique [Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service Histologie-embryologie-cytogénétique, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], CHU Trousseau [APHP], Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), 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), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Cytogénétique Constitutionnelle [Hospices civils de Lyon], Hospices Civils de Lyon (HCL), CHU de Lyon, Centre Hospitalier Universitaire [Grenoble] (CHU), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de génétique médicale [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier de Chambéry (C.H.de Chambéry), Service de génétique clinique [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, Génétique médicale [Centre Hospitalier de Vannes], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Centre Hospitalier Le Mans (CH Le Mans), AP-HP Hôpital universitaire Robert-Debré [Paris], Service Psychiatrie de l'Enfant et de l'Adolescent, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, UF de Cytogénétique, Institut Pasteur [Paris], Université de Bordeaux (UB), École normale supérieure - Rennes (ENS Rennes), Unité de Mathématique, Informatique et Génome (MIG), Institut National de la Recherche Agronomique (INRA), Laboratoire Interdisciplinaire Carnot de Bourgogne (LICB), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de génétique clinique [Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré, Service de Génétique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de génétique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service de génétique, cytogénétique, embryologie [Pitié-Salpétrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Institut de Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de Génétique et d'Embryologie Médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Gatonero SA, Hôtel-Dieu de Nantes, Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique Médicale, CHU Clermont-Ferrand-Hôpital d'Estaing, Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de génétique chromosomique [Hôpital de la Timone - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de référence des anomalies du développement [Lyon], UF de Biochimie et Génétique Moléculaire (BGM), CHU Grenoble, Dynamique Cellulaire et Tissulaire- Interdisciplinarité, Modèles & Microscopies (TIMC-IMAG-DyCTiM), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), IMAXIO, Maladies rares, génétique et métabolisme / Rare Diseases, Genetics and Metabolism, École de sage femme - Groupe hospitalier Pellegrin - CHU de Bordeaux-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Universitaire Carémeau [Nîmes], Département de Génétique Chromosomique, Bâtiment Hôtel Dieu - Centre Hospitalier de Chambéry, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Hôpital Sud, CLAD Ouest, Centre Hospitalier Universitaire [Rennes], Centre Hospitalier Bretagne Atlantique [Vannes], Génétique Humaine et Fonctions Cognitives, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de génétique, cytogénétique, embryologie [CHU Pitié-Salpétrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Rolland, Thomas
Subjects: medicine.medical_specialty, lcsh:QH426-470, lcsh:Medicine, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Article, 03 medical and health sciences, 0302 clinical medicine, Phelan-McDermid syndrome, Genetics, medicine, 0501 psychology and cognitive sciences, In patient, Clinical genetics, Author Correction, Psychiatry, Molecular Biology, Genetics (clinical), business.industry, lcsh:R, Neurodevelopmental disorders, 05 social sciences, lcsh:Genetics, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Medical genetics, business, 030217 neurology & neurosurgery, 050104 developmental & child psychology
Abstract: Phelan-McDermid syndrome (PMS) is characterized by a variety of clinical symptoms with heterogeneous degrees of severity, including intellectual disability (ID), absent or delayed speech, and autism spectrum disorders (ASD). It results from a deletion of the distal part of chromosome 22q13 that in most cases includes the SHANK3 gene. SHANK3 is considered a major gene for PMS, but the factors that modulate the severity of the syndrome remain largely unknown. In this study, we investigated 85 patients with different 22q13 rearrangements (78 deletions and 7 duplications). We first explored the clinical features associated with PMS, and provide evidence for frequent corpus callosum abnormalities in 28% of 35 patients with brain imaging data. We then mapped several candidate genomic regions at the 22q13 region associated with high risk of clinical features, and suggest a second locus at 22q13 associated with absence of speech. Finally, in some cases, we identified additional clinically relevant copy-number variants (CNVs) at loci associated with ASD, such as 16p11.2 and 15q11q13, which could modulate the severity of the syndrome. We also report an inherited SHANK3 deletion transmitted to five affected daughters by a mother without ID nor ASD, suggesting that some individuals could compensate for such mutations. In summary, we shed light on the genotype-phenotype relationship of patients with PMS, a step towards the identification of compensatory mechanisms for a better prognosis and possibly treatments of patients with neurodevelopmental disorders., The underlying genetics of Phelan-McDermid syndrome Multiple chromosomal changes may impact the severity of symptoms in people with Phelan-McDermid syndrome (PMS). Thomas Bourgeron of the Institut Pasteur and colleagues in France conducted genomic analyses and explored the clinical features of 85 people with PMS, a condition caused by a deletion in the long arm of chromosome 22. It is often associated with severe symptoms such as intellectual disability, autism, and seizures. The chromosomal changes in 65% of those studied were not inherited. MRI brain scans showed visible abnormalities in 23 of 35 patients imaged. The size of the chromosomal deletion varied. Patients with small deletions were more likely to have autistic symptoms while those with large deletions were more likely to be unable to talk. The team also identified genes in chromosome 22 and in other regions of the genome that could modify the severity of PMS symptoms.
Published: 2019

49. Time course of fluid responsiveness in sepsis: the fluid challenge revisiting (FCREV) study

Author: Claire, Roger, Laurent, Zieleskiewicz, Christophe, Demattei, Karim, Lakhal, Gael, Piton, Benjamin, Louart, Jean-Michel, Constantin, Russell, Chabanne, Jean-Sébastien, Faure, Yazine, Mahjoub, Isabelle, Desmeulles, Hervé, Quintard, Jean-Yves, Lefrant, Laurent, Muller, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Service de gastro-entérologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Service d'Anésthésie Réanimation [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, CHU Clermont-Ferrand, Service de dermatologie [CHU d'Amiens-Picardie], CHU Amiens-Picardie, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Prémilleux, Annick, Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Time Factors, [SDV]Life Sciences [q-bio], Fluid responsiveness, Hemodynamics, Critical Care and Intensive Care Medicine, law.invention, 0302 clinical medicine, 030202 anesthesiology, law, Prospective Studies, Cardiac Output, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Shock, Stroke volume, Middle Aged, Intensive care unit, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, [SDV] Life Sciences [q-bio], Intensive Care Units, Editorial Commentary, Echocardiography, Anesthesia, Shock (circulatory), Female, SOFA score, France, medicine.symptom, Subgroup analysis, Sepsis, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine, Humans, Arterial Pressure, Fluid challenge, Aged, business.industry, Septic shock, 030208 emergency & critical care medicine, lcsh:RC86-88.9, Crystalloid Solutions, medicine.disease, 13. Climate action, ICU, Fluid Therapy, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Fluid challenge (FC) is one of the most common practices in Intensive Care Unit (ICU). The present study aimed to evaluate whether echocardiographic assessment of the response to FC at the end of the infusion or 20 min later could affect the results of the FC. This is a prospective, observational, multicenter study including all ICU patients in septic shock requiring a FC of 500 mL crystalloids over 10 min. Fluid responsiveness was defined as a > 15% increase in stroke volume (SV) assessed by velocity-time integral (VTI) measurements at baseline (T0), at the end of FC (T10), then 10 (T20) and 20 min (T30) after the end of FC. From May 20, 2014, to January 7, 2016, a total of 143 patients were enrolled in 11 French ICUs (mean age 64 ± 14 years, median IGS II 53 [43–63], median SOFA score 10 [8–12]). Among the 76/143 (53%) patient responders to FC at T10, 37 patients were transient responders (TR), i.e., became non-responders (NR) at T30 (49%, 95%CI = [37–60]), and 39 (51%, 95%CI = [38–62]) patients were persistent responders (PR), i.e., remained responders at T30. Among the 67 NR at T10, 4 became responders at T30, (6%, 95%CI = [1.9–15.3]). In the subgroup analysis, no statistical difference in hemodynamic and echocardiographic parameters was found between groups. This study shows that 51.3% of initial responders have a persistent response to fluid 30 min after the beginning of fluid infusion and only 41.3% have a transient response highlighting that fluid responsiveness is time dependent. ClinicalTrials.gov , NCT02116413 . Registered on April 16, 2014
Published: 2019

50. Health-related quality of life as an endpoint in oncology phase I trials: a systematic review

Author: Amélie Anota, Ahmad Ousmen, Franck Bonnetain, Isabelle Le Ray, Nicolas Isambert, Frédéric Fiteni, Department of Medical Oncology [Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM), Department of Neonatology [Strasbourg], CHU Strasbourg, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Unité de Méthodologie et de Qualité de Vie en Cancérologie (UMQVC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), 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)-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)-Pôle cancérologie (CHRU Besançon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut Régional Fédératif du Cancer (IRFC), Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, French National Platform Quality of Life and Cancer [Dijon], Bodescot, Myriam, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut Régional Fédératif du Cancer (IRFC), and Plateforme nationale qualité de vie et cancer
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Health-related quality of life, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, Phase I trial, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Quality of life, Surgical oncology, Neoplasms, Surveys and Questionnaires, Internal medicine, Outcome Assessment, Health Care, Recommended phase II dose, Genetics, medicine, Humans, Adverse effect, Neoplasm Staging, Health related quality of life, Clinical Trials, Phase I as Topic, business.industry, Minimal clinically important difference, Repeated measures design, Common Terminology Criteria for Adverse Events, Phase i trials, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Endpoint, Combined Modality Therapy, humanities, 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Treatment Outcome, 030104 developmental biology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, Quality of Life, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Research Article
Abstract: International audience; BACKGROUND:Phase I trials aim to identify the recommended dose for further development. Health-related quality of life (HRQoL) could be a complement to the usual National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) scale to detect adverse events and define the doses. The objective of this study is to review the phase I in oncology which used HRQoL as endpoint.METHODS:A search in PubMed database identified phase I trials in oncology with HRQoL as endpoint, published between January 2012 to May 2016. Hematological and pediatric phase I were excluded.RESULTS:A total of 1333 phase I were identified and 15 trials were identified with HRQoL as endpoint (1.1%). The European Organisation for Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) was the most frequently used instrument: 5 studies (33.3%). The targeted dimensions of HRQoL and the minimal clinically important difference were prespecified in 1 study (6.7%) and 2 studies (13.3%), respectively. Twelve studies (80%) described the statistical approach to analyze HRQoL data. Eight studies used the mean change from baseline (60%) to analyse longitudinal HRQoL data, two the mean score at certain times (13.3%), one the linear mixed model for repeated measures (6.7%), one the time to HRQoL score deterioration (6.7%), one percentage of patient-reported symptoms (6.7%). None of the studies used HRQoL to determine the recommended doses.CONCLUSION:Few phase I studies used HRQoL as endpoint and among studies with HRQoL as endpoint, the methodology of HRQoL measurement and statistical analysis was heterogeneous. HRQoL. endpoint not used for assessing the recommended phase II doses.
Published: 2019

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