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722 results on '"Unité de biostatistiques"'

1. Transcriptional alterations in glioma result primarily from DNA methylation–independent mechanisms

Author: Mélanie Müller-Barthélémy, Elisa Le Boiteux, Franck Court, Julian Biau, Lucie Karayan-Tapon, Toufic Khalil, Pierre Verrelle, Philippe Arnaud, Jean-Louis Kemeny, Anne Fogli, Catherine Vaurs-Barrière, Bruno Pereira, Emmanuel Chautard, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Thérapie ciblée combinatoire en Onco-Hématologie (EA3846), Université d'Auvergne - Clermont-Ferrand I (UdA), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Laboratoire de pathologie, Service de Neurochirurgie [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Institut National de la Transfusion Sanguine [Paris] (INTS), Arnaud, Philippe, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Service de Biochimie Médicale et Biologie Moléculaire [CHU Clermont-Ferrand], Centre Jean Perrin, CRLCC Jean Perrin, Unité de biostatistiques, CHU Clermont-Ferrand-Hôpital Montpied, Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), CHU Clermont-Ferrand-Hôpital Gabriel Montpied, Service de Neurochirurgie [CHU Clermont-Ferrand], ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, Jumonji Domain-Containing Histone Demethylases, Transcription, Genetic, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease_cause, Epigenesis, Genetic, Histones, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, medicine, Humans, transcriptional defects, Epigenetics, Promoter Regions, Genetic, Gene, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), 030304 developmental biology, 0303 health sciences, Mutation, Research, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], Promoter, Glioma, DNA Methylation, Chromatin, Isocitrate Dehydrogenase, 3. Good health, Cell biology, Gene Expression Regulation, Neoplastic, [SDV.BBM.MN] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], CpG site, CpG-island, Cancer cell, DNA methylation, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], CpG Islands, Female, 030217 neurology & neurosurgery, Bivalent chromatin
Abstract: In cancer cells, aberrant DNA methylation is commonly associated with transcriptional alterations, including silencing of tumor suppressor genes. However, multiple epigenetic mechanisms, including polycomb repressive marks, contribute to gene deregulation in cancer. To dissect the relative contribution of DNA methylation–dependent and –independent mechanisms to transcriptional alterations at CpG island/promoter-associated genes in cancer, we studied 70 samples of adult glioma, a widespread type of brain tumor, classified according to their isocitrate dehydrogenase (IDH1) mutation status. We found that most transcriptional alterations in tumor samples were DNA methylation–independent. Instead, altered histone H3 trimethylation at lysine 27 (H3K27me3) was the predominant molecular defect at deregulated genes. Our results also suggest that the presence of a bivalent chromatin signature at CpG island promoters in stem cells predisposes not only to hypermethylation, as widely documented, but more generally to all types of transcriptional alterations in transformed cells. In addition, the gene expression strength in healthy brain cells influences the choice between DNA methylation- and H3K27me3-associated silencing in glioma. Highly expressed genes were more likely to be repressed by H3K27me3 than by DNA methylation. Our findings support a model in which altered H3K27me3 dynamics, more specifically defects in the interplay between polycomb protein complexes and the brain-specific transcriptional machinery, is the main cause of transcriptional alteration in glioma cells. Our study provides the first comprehensive description of epigenetic changes in glioma and their relative contribution to transcriptional changes. It may be useful for the design of drugs targeting cancer-related epigenetic defects.
Published: 2019

2. Circulating 20S proteasome for assessing protein energy wasting syndrome in hemodialysis patients

Author: Marine Freist, Elodie Gentes, Carole Philipponnet, Mohamed Hadj Abdelkader, Bruno Pereira, Aurélien Piraud, Cyril Garrouste, Anne-Elisabeth Heng, Julien Aniort, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Emile Roux [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie - Hémodialyses [CHU Clermont-Ferrand], Pôle RHEUNNIRS [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Dept Clin Nutr, Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Unité de Biostatistiques, Direction de la Recherche Clinique (DRCI)
Subjects: Male, 0301 basic medicine, dialyse, [SDV]Life Sciences [q-bio], medicine.medical_treatment, 030232 urology & nephrology, Muscle Proteins, Biochemistry, protéasome, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Gastroenterology, 0302 clinical medicine, Medicine and Health Sciences, 2. Zero hunger, Multidisciplinary, Protein energy wasting, Muscle Analysis, Middle Aged, C-Reactive Proteins, Muscle atrophy, atrophie musculaire, 3. Good health, Hospitalization, Bioassays and Physiological Analysis, Nephrology, Creatinine, Medicine, Female, patient, Hemodialysis, medicine.symptom, Research Article, Proteasome Endopeptidase Complex, medicine.medical_specialty, Science, Nutritional Status, Circulating Proteasome, Research and Analysis Methods, Protein-Energy Malnutrition, 03 medical and health sciences, Signs and Symptoms, Renal Dialysis, Internal medicine, Medical Dialysis, medicine, Humans, Mortality, Survival rate, Nutrition, Aged, Wasting Syndrome, business.industry, Biology and Life Sciences, Proteins, Protein Complexes, Proteasomes, medicine.disease, perte d'énergie, Patient Outcome Assessment, 030104 developmental biology, Proteasome, Clinical Medicine, Atrophy, Complication, business, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Kidney disease
Abstract: International audience; Protein energy wasting (PEW) including muscle atrophy is a common complication in chronic hemodialysis patients. The ubiquitin proteasome system (UPS) is the main proteolytic system causing muscle atrophy in chronic kidney disease and proteasome 20S is the catalytic component of the UPS. Circulating proteasome 20S (c20S proteasome) is present in the blood and its level is related to disease severity and prognosis in several disorders. We hypothesized that c20S proteasome could be related with muscle mass, other PEW criteria and their evolution in hemodialysis patients. Stable hemodialysis patients treated at our center for more than 3 months were followed over 2 years. C20S proteasome assay was performed at baseline. Biological and clinical data were collected, muscle mass was assessed by multi-frequency bio-impedancemetry, and nutritional scores were calculated at baseline, 1 year and 2 years. Hospitalizations and mortality data were collected over the 2 years. Forty-nine patients were included. At baseline, the c20S proteasome level was 0.40 [0.26-0.55] mu g/ml. Low muscle mass as defined by a lean tissue index (LTI) < 10th in accordance with the International Society of Renal Nutrition and Metabolism guidelines was observed in 36% and PEW in 62%. Increased c20S proteasome levels were related with LTI at baseline (R = 0.43, p = 0.004) and with its 2 year-variation (R = -0.56, p = 0.003). Two-year survival rate was not different between higher and lower c20S proteasome values (78.9 vs 78.4%, p = 0.98 log-rank test). C20S proteasome is not a good marker for assessing nutritional status in hemodialysis patients and predicting patient outcomes.
Published: 2020

3. Stress management in obesity during a thermal spa residential programme (ObesiStress): protocol for a randomised controlled trial study

Author: Yves Boirie, Daniela M. Pfabigan, Omar Izem, Magalie Miolanne-Debouit, N. Farigon, Bruno Pereira, Laurie Mobdillon, Guillaume T. Vallet, Armand Abergel, Pascale Duché, Gil Boudet, Philippe Obert, Shihui Han, Elodie Chaplais, Daniel Courteix, Frédéric Dutheil, Audrey Vilmant, Martial Mermillod, Laboratoire de Psychologie Sociale et Cognitive - Clermont Auvergne (LAPSCO), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut de Médecine du Travail, CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), Laboratoire Développement, Adaptation et Handicap (DevAH), Unité de Biostatistiques [CHU Clermont-Ferrand] (Département de la recherche clinique et de l'innovation - DRCI), CHU Clermont-Ferrand, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Faculté des Sciences du SportFaculté des Sciences du Sport, UFR STAPS, Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Impact de l'Activité Physique sur la Santé (IAPS), Université de Toulon (UTLN), Service d'Hépato-Gastroentérologie [CHRU Clermont-Ferrand], Centre Hospitalier Universitaire de Clermont-Ferrand, Peking University [Beijing], PKU-IDG/McGovern Institute For Brain Research, Centre de recherche en économie de Grenoble (CREG), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Grenoble Alpes (UGA), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Physiopathologie des adaptations cardiovasculaires à l'Exercice, Avignon Université (AU), EA4278 Laboratoire de Pharm-Ecologie Cardiovasculaire (LaPEC), Nutrition clinique, Centre Hospitalier Universitaire Gabriel Montpied, nutrition clinique, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Université Clermont Auvergne (UCA), Centre National de la Recherche Scientifique (CNRS), Service Santé Travail Environnement, EA 3450, Université de Lorraine (UL), Département Recherche Clinique et Innovation, EA 3533, Laboratoire des Adaptations Métaboliques à l’Exercice en conditions Physiologiques et Pathologiques (AME2P), Laboratoire Impact de l’Activité Physique sur la Santé, Hépatologie Gastro-Entérologie, Centre Hospitalier Universitaire Estaing, UMR 6284, University Beijing, Laboratoire de Psychologie et NeuroCognition (LPNC), Université Grenoble Alpes (COMUE) (UGA), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), EA 4278, laboratoire de Pharm-Ecologie Cardiovasculaire (LaPEC ), Biostatistiques, Danone Research, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Université Clermont Auvergne (UCA)-Institut National de la Recherche Agronomique (INRA), Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Développement, Adaptation et Handicap. Régulations cardio-respiratoires et de la motricité (DevAH), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Ferrand (UFR STAPS - UBP), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Auvergne Rhone-Alpes University Hospital of Clermont-Ferrand European Regional Development Fund (Fonds Europeen de Developpement Economique et Regional), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Ferrand (UFR STAPS - UBP), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), and Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA)
Subjects: musculoskeletal diseases, Stress management, medicine.medical_specialty, obesity, Cardiovascular Medicine, Overweight, Body Mass Index, law.invention, 03 medical and health sciences, stress, 0302 clinical medicine, Quality of life, Randomized controlled trial, prevention, Heart Rate, law, Protocol, Humans, Medicine, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Randomized Controlled Trials as Topic, 2. Zero hunger, business.industry, Public health, heart rate variability, Hyperthermia, Induced, General Medicine, Anthropometry, medicine.disease, Obesity, 3. Good health, spa bath, Body Composition, Quality of Life, Physical therapy, France, medicine.symptom, business, Body mass index, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Biomarkers, Stress, Psychological, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: IntroductionStress and obesity are two public health issues. The relationship between obesity and stress is biological through the actions of stress on the major hormones that regulate appetite (leptin and ghrelin). Many spa resorts in France specialise in the treatment of obesity, but no thermal spa currently proposes a specific programme to manage stress in obesity. The ObesiStress protocol has been designed to offer a new residential stress management programme. This thermal spa treatment of obesity implements stress management strategies as suggested by international recommendations.Methods and analysis140 overweight or obese participants with a Body Mass Index of >25 kg/m2 and aged over 18 years will be recruited. Participants will be randomised into two groups: a control group of usual practice (restrictive diet, physical activity and thermal spa treatment) and an intervention group with stress management in addition to the usual practice. In the present protocol, parameters will be measured on five occasions (at inclusion, at the beginning of the spa (day 0), at the end of the spa (day 21), and at 6 and 12 months). The study will assess the participants’ heart rate variability, cardiac remodelling and function, electrodermal activity, blood markers, anthropometric profile, body composition, psychology and quality of life via the use of questionnaires and bone parameters.Ethics and disseminationThe ObesiStress protocol complies with the ethics guidelines for Clinical Research and has been approved by the ethics committee (CPP Sud-Est VI, Clermont-Ferrand - ANSM: 2016-A01774-47). This study aimed to highlight the efficacy of a 21-day thermal spa residential programme of stress management in obesity through objective measurements of well-being and cardiovascular morbidity. Results will be disseminated during several research conferences and articles published in peer-reviewed journals.Trial registration numberNCT03578757.
Published: 2019

4. Excision versus colorectal resection in deep endometriosis infiltrating the rectum:5-year follow-up of patients enrolled in a randomized controlled trial

Author: Horace Roman, Haitham Khalil, Lacramioara Aurelia Branduse, Valérie Bridoux, Emmanuel Huet, Jean-Jacques Tuech, Michael Bubenheim, Clotilde Hennetier, Gamétogenèse et Qualité du Gamète - ULR 4308 (GQG), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Lille, Service de gynécologie et obstétrique [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Laboratoire d'éthique médicale et médecine légale (LEM), Université Paris Descartes - Paris 5 (UPD5), Service de chirurgie digestive [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Unité de biostatistiques [CHU Rouen], University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), Gamétogenèse et Qualité du Gamète (GQG), Normandie Université (NU)-Normandie Université (NU)-Université de Lille, Droit et Santé-Université de Lille, Service de gynécologie et obstétrique [Rouen], Service de chirurgie digestive [Rouen], and Unité de biostatistiques [Rouen]
Subjects: Adult, medicine.medical_specialty, Endometriosis, Rectum, bladder dysfunction, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Pelvic Pain, law.invention, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Randomized controlled trial, law, Recurrence, medicine, Clinical endpoint, Dysuria, Humans, Digestive System Surgical Procedures, colorectal resection, 030219 obstetrics & reproductive medicine, business.industry, Rehabilitation, Obstetrics and Gynecology, shaving, medicine.disease, Anus, 3. Good health, Surgery, medicine.anatomical_structure, Rectal Diseases, Treatment Outcome, digestive symptoms, Reproductive Medicine, 030220 oncology & carcinogenesis, Defecation, Female, France, disc excision, Segmental resection, medicine.symptom, business, Corrigendum, Colorectal Surgery, Follow-Up Studies
Abstract: STUDY QUESTION Is there a difference in functional outcomes and recurrence rate between conservative versus radical rectal surgery in patients with large deep endometriosis infiltrating the rectum 5 years postoperatively? SUMMARY ANSWER No evidence was found that long-term outcomes differed when nodule excision was compared to rectal resection for deeply invasive endometriosis involving the bowel. WHAT IS KNOWN ALREADY Functional outcomes of nodule excision and rectal resection for deeply invasive endometriosis involving the bowel are comparable 2 years after surgery. Despite numerous previously reported case series enrolling patients managed for colorectal endometriosis, long-term data remain scarce in the literature. STUDY DESIGN, SIZE, DURATION From March 2011 to August 2013, we performed a two-arm randomized trial, enrolling 60 patients with deep endometriosis infiltrating the rectum up to 15 cm from the anus, measuring >20 mm in length, involving at least the muscular layer in depth, and up to 50% of rectal circumference. Among them, 55 women were enrolled at one tertial referral centre in endometriosis, using a randomization list drawn up separately for this centre. Institute review board approval was obtained to continue follow-up to 10 years postoperatively. One patient requested to stop the follow-up 2 years after surgery. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients underwent either nodule excision by shaving or disc excision, or segmental resection. Randomization was performed preoperatively using sequentially numbered, opaque, sealed envelopes, and patients were informed of randomization results. The primary endpoint was the proportion of patients experiencing one of the following symptoms: constipation (1 stool/>5 consecutive days), frequent bowel movements (≥3 stools/day), anal incontinence, dysuria or bladder atony requiring self-catheterization 24 months postoperatively. Secondary endpoints were values taken from the Knowles–Eccersley–Scott-symptom questionnaire (KESS), the gastrointestinal quality of life index (GIQLI), the Wexner scale, the urinary symptom profile (USP) and the Short Form 36 Health Survey (SF36). MAIN RESULTS AND THE ROLE OF CHANCE Fifty-five patients were enrolled. Among the 27 patients in the excision arm, two were converted to segmental resection (7.4%). One patient managed by segmental resection withdrew from the study 2 years postoperatively, presuming that associated pain of other aetiologies may have jeopardized the outcomes. The 5 year-recurrence rate for excision and resection was 3.7% versus 0% (P = 1), respectively. For excision and resection, the primary endpoint was present in 44.4% versus 60.7% of patients (P = 0.29), respectively, while 55.6% versus 53.6% of patients subjectively reported normal bowel movements (P = 1). An intention-to-treat comparison of overall KESS, GIQLI, Wexner, USP and SF36 scores did not reveal significant differences between the two arms 5 years postoperatively. Statistically significant improvement was observed shortly after surgery with no further improvement or impairment recorded 1–5 years postoperatively. During the 5-year follow-up, additional surgical procedures were performed in 25.9% versus 28.6% of patients who had undergone excision or resection (P = 0.80), respectively. LIMITATIONS, REASONS FOR CAUTION The presumption of a 40% difference concerning postoperative functional outcomes in favour of nodule excision resulted in a lack of power for demonstration of the primary endpoint difference. WIDER IMPLICATIONS OF THE FINDINGS Five-year follow-up data do not show statistically significant differences between conservative and radical rectal surgery for long-term functional digestive and urinary outcomes in this specific population of women with large involvement of the rectum. STUDY FUNDING/COMPETING INTEREST(S) No specific funding was received. Patient enrolment and follow-up until 2 years postoperatively was supported by a grant from the clinical research programme for hospitals in France. The authors declare no competing interests related to this study. TRIAL REGISTRATION NUMBER This randomized study is registered with ClinicalTrials.gov, number NCT 01291576. TRIAL REGISTRATION DATE 31 January 2011. DATE OF FIRST PATIENT’S ENROLMENT 7 March 2011.
Published: 2019

5. Sedation versus general anaesthesia in endovascular therapy for anterior circulation acute ischaemic stroke: the multicentre randomised controlled AMETIS trial study protocol

Author: Franck Verdonk, Bruno Pereira, Aurélie Masgrau, Anne-Claire Lukaszewicz, Serge Molliex, Samir Jaber, Ségolène Mrozek, Emmanuel Futier, Russell Chabanne, Lionel Velly, Elodie Caumon, Emmanuel Chabert, Charlotte Fernandez-Canal, Jean-Etienne Bazin, Anna Ferrier, Claire Dahyot-Fizelier, Pierre-François Perrigault, Marc Begard, Benoît Tavernier, Vincent Degos, CHU Clermont-Ferrand, Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques - EA 7426 (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Assistance Publique - Hôpitaux de Marseille (APHM), Département d'Anesthésie-Réanimation [Toulouse], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Gabriel Montpied [Clermont-Ferrand], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Anésthésie Réanimation [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), MORNET, Dominique, Pôle Anesthésie Réanimation [CHU de Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique Hôpitaux de Paris (AP-HP)Assistance Publique Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié-Salpêtrière, Paris, France., Centre Hospitalier Universitaire de Clermont-Ferrand, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), CHU Gabriel Montpied (CHU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de réanimation adulte, département d'anesthésie-réanimation, CHU Clermont-Ferrand-Hôtel Dieu, Unité de biostatistiques, CHU Clermont-Ferrand-Hôpital Montpied, Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Adult, Male, Mechanical Thrombolysis, Sedation, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Conscious Sedation, Anesthesia, General, Anaesthesia, 03 medical and health sciences, 0302 clinical medicine, Modified Rankin Scale, medicine, Protocol, Humans, Multicenter Studies as Topic, General anaesthesia, 030212 general & internal medicine, Myocardial infarction, Stroke, Randomized Controlled Trials as Topic, business.industry, Endovascular Procedures, General Medicine, Thrombolysis, Perioperative, medicine.disease, stroke, 3. Good health, anaesthesia in neurology, [SDV] Life Sciences [q-bio], sedation, thrombectomy, Anesthesia, Observational study, Female, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: IntroductionEndovascular thrombectomy is the standard of care for anterior circulation acute ischaemic stroke (AIS) secondary to emergent large vessel occlusion in patients who qualify. General anaesthesia (GA) or conscious sedation (CS) is usually required to ensure patient comfort and avoid agitation and movement during thrombectomy. However, the question of whether the use of GA or CS might influence functional outcome remains debated. Indeed, conflicting results exist between observational studies with better outcomes associated with CS and small monocentric randomised controlled trials favouring GA. Therefore, we aim to evaluate the effect of CS versus GA on functional outcome and periprocedural complications in endovascular mechanical thrombectomy for anterior circulation AIS.Methods and analysisAnesthesia Management in Endovascular Therapy for Ischemic Stroke (AMETIS) trial is an investigator initiated, multicentre, prospective, randomised controlled, two-arm trial. AMETIS trial will randomise 270 patients with anterior circulation AIS in a 1:1 ratio, stratified by centre, National Institutes of Health Stroke Scale (≤15 or >15) and association of intravenous thrombolysis or not to receive either CS or GA. The primary outcome is a composite of functional independence at 3 months and absence of perioperative complication occurring by day 7 after endovascular therapy for anterior circulation AIS. Functional independence is defined as a modified Rankin Scale score of 0–2 by day 90. Perioperative complications are defined as intervention-associated arterial perforation or dissection, pneumonia or myocardial infarction or cardiogenic acute pulmonary oedema or malignant stroke evolution occurring by day 7.Ethics and disseminationThe AMETIS trial was approved by an independent ethics committee. Study began in august 2017. Results will be published in an international peer-reviewed medical journal.Trial registration numberNCT03229148.
Published: 2019

6. Personalised mechanical ventilation tailored to lung morphology versus low positive end-expiratory pressure for patients with acute respiratory distress syndrome in France (the LIVE study): a multicentre, single-blind, randomised controlled trial

Author: Jean-Michel Constantin, Matthieu Jabaudon, Jean-Yves Lefrant, Samir Jaber, Jean-Pierre Quenot, Olivier Langeron, Martine Ferrandière, Fabien Grelon, Philippe Seguin, Carole Ichai, Benoit Veber, Bertrand Souweine, Thomas Uberti, Sigismond Lasocki, François Legay, Marc Leone, Nathanael Eisenmann, Claire Dahyot-Fizelier, Hervé Dupont, Karim Asehnoune, Achille Sossou, Gérald Chanques, Laurent Muller, Jean-Etienne Bazin, Antoine Monsel, Lucile Borao, Jean-Marc Garcier, Jean-Jacques Rouby, Bruno Pereira, Emmanuel Futier, Cayot Sophie, Godet Thomas, Guerin Renaud, Verlac Camille, Chabanne Russel, Cosserant Bernard, Blondonnet Raiko, Lautrette Alexandre, Eisenmann Nathanael, Muller Laurent, Massanet Pablo, Boutin Caroline, Barbar Saber, Roger Claire, Belafia Fouad, Cisse Moussa, Monnin Marion, Conseil Matthieu, Carr Julie, De Jong Audrey, Dargent Auguste, Andreu Pascal, Lebouvrier Thomas, Launey Yoann, Roquilly Antoine, Cinotti Raphael, Tellier Anne-Charlotte, Barbaz Mathilde, Cohen Benjamin, Lemarche Edouard, Bertrand Pierre-Marie, Arberlot Charlotte, Zieleskiewicz Laurent, Hammad Emmanuelle, Duclos Garry, Mathie Calypso, Dupont Herve, Veber Benoit, Orban Jean-Christophe, Quintard Hervé, Rimmele Thomas, Crozon-Clauzel Julien, Le Core Marinne, Grelon Fabien, Assefi Mona, Petitas Frank, Morel Jerome, Molliex Serge, Hadanou Nanadougmar, CHU Clermont-Ferrand, Service d'Anésthésie Réanimation [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Le Mans (CH Le Mans), CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de réanimation, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital St Roch, Département d'anesthésie-Réanimation-Samu, CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Unité de soins intensifs [Clermont Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Edouard Herriot Hospital, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU de Saint-Brieuc, Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, 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), Department of Anesthesiology and Critical Care Medicine, Emile-Roux general hospital, Le Puy-en-Velay, Université de Montpellier (UM), Immunologie - Immunopathologie - Immunothérapie (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Department of Perioperative Medicine, CHU Clermont-Ferrand, CHU Pitié-Salpêtrière [APHP], Hopital Général, Le Mans, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand-Hôpital Gabriel Montpied, Hospital General Saint-Brieuc, Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Centre Régional de Lutte Contre le Cancer Jean Perrin, Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Service de réanimation adulte, département d'anesthésie-réanimation, CHU Clermont-Ferrand-Hôtel Dieu, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), University Hospital of Clermont-Ferrand, Institut Pascal - Clermont Auvergne (IP), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Unité de biostatistiques, CHU Clermont-Ferrand-Hôpital Montpied, Génétique, Reproduction et Développement - Clermont Auvergne (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), MORNET, Dominique, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, ARDS, medicine.medical_treatment, [SDV]Life Sciences [q-bio], law.invention, Positive-Pressure Respiration, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Fraction of inspired oxygen, Intensive care, medicine, Prone Position, Tidal Volume, Humans, Single-Blind Method, 030212 general & internal medicine, Prospective Studies, Precision Medicine, Lung, Positive end-expiratory pressure, Tidal volume, ComputingMilieux_MISCELLANEOUS, Proportional Hazards Models, Mechanical ventilation, Respiratory Distress Syndrome, business.industry, Hazard ratio, Middle Aged, medicine.disease, Respiration, Artificial, 3. Good health, [SDV] Life Sciences [q-bio], Intensive Care Units, Editorial Commentary, Treatment Outcome, 030228 respiratory system, Female, France, business
Abstract: The effect of personalised mechanical ventilation on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remains uncertain and needs to be evaluated. We aimed to test whether a mechanical ventilation strategy that was personalised to individual patients' lung morphology would improve the survival of patients with ARDS when compared with standard of care.We designed a multicentre, single-blind, stratified, parallel-group, randomised controlled trial enrolling patients with moderate-to-severe ARDS in 20 university or non-university intensive care units in France. Patients older than 18 years with early ARDS for less than 12 h were randomly assigned (1:1) to either the control group or the personalised group using a minimisation algorithm and stratified according to the study site, lung morphology, and duration of mechanical ventilation. Only the patients were masked to allocation. In the control group, patients received a tidal volume of 6 mL/kg per predicted bodyweight and positive end-expiratory pressure (PEEP) was selected according to a low PEEP and fraction of inspired oxygen table, and early prone position was encouraged. In the personalised group, the treatment approach was based on lung morphology; patients with focal ARDS received a tidal volume of 8 mL/kg, low PEEP, and prone position. Patients with non-focal ARDS received a tidal volume of 6 mL/kg, along with recruitment manoeuvres and high PEEP. The primary outcome was 90-day mortality as established by intention-to-treat analysis. This study is registered online with ClinicalTrials.gov, NCT02149589.From June 12, 2014, to Feb 2, 2017, 420 patients were randomly assigned to treatment. 11 patients were excluded in the personalised group and nine patients were excluded in the control group; 196 patients in the personalised group and 204 in the control group were included in the analysis. In a multivariate analysis, there was no difference in 90-day mortality between the group treated with personalised ventilation and the control group in the intention-to-treat analysis (hazard ratio [HR] 1·01; 95% CI 0·61-1·66; p=0·98). However, misclassification of patients as having focal or non-focal ARDS by the investigators was observed in 85 (21%) of 400 patients. We found a significant interaction between misclassification and randomised group allocation with respect to the primary outcome (p0·001). In the subgroup analysis, the 90-day mortality of the misclassified patients was higher in the personalised group (26 [65%] of 40 patients) than in the control group (18 [32%] of 57 patients; HR 2·8; 95% CI 1·5-5·1; p=0·012.Personalisation of mechanical ventilation did not decrease mortality in patients with ARDS, possibly because of the misclassification of 21% of patients. A ventilator strategy misaligned with lung morphology substantially increases mortality. Whether improvement in ARDS phenotyping can decrease mortality should be assessed in a future clinical trial.French Ministry of Health (Programme Hospitalier de Recherche Clinique InterRégional 2013).
Published: 2019

7. Designing phase II clinical trials to target subgroup of interest in a heterogeneous population: A case study using an R package

Author: Patrick Sfumato, Jean-Marie Boher, Bastien Cabarrou, Eve Leconte, Thomas Filleron, Unité de Biostatistiques [Toulouse] ( Institut Claudius Regaud / IUCT-O), Institut Claudius Regaud-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)-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), Unité de Biostatistiques [Institut Paoli-Calmettes] (Département de la Recherche clinique et de l'Innovation), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Toulouse School of Economics (TSE-R), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), We would like to thank ‘‘La Ligue Nationale Contre le Cancer, France’’ (Comité des Pyrénées-Orientales, Comité de la Meuse, Comité du Maine-et-Loire) for their financial support.This study was funded by ‘‘La Ligue Nationale Contre le Cancer, France’’ (PI: Thomas Filleron)., Institut Claudius Regaud-Institut Universitaire du Cancer Toulouse - Oncopôle (IUCT), Toulouse School of Economics (TSE), École des hautes études en sciences sociales (EHESS)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1), Institut Universitaire du Cancer Toulouse - Oncopôle (IUCT)-Institut Claudius Regaud, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Dupuis, Christine, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Computer science, Population, Phases of clinical research, Health Informatics, Target population, Machine learning, computer.software_genre, 01 natural sciences, Molecular heterogeneity, 010104 statistics & probability, 03 medical and health sciences, Clinical Trials, Phase II as Topic, 0302 clinical medicine, Neoplasms, Biomarkers, Tumor, Humans, 030212 general & internal medicine, Target therapy, 0101 mathematics, education, education.field_of_study, business.industry, R package, Simon two-stage design, Phase II clinical trial, 3. Good health, Computer Science Applications, Single-arm, Heterogeneous population, Target subgroup, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Biomarker (medicine), [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Artificial intelligence, Heterogeneity, business, computer, Stratified adaptive design
Abstract: International audience; Phase II trials that evaluate target therapies based on a biomarker must be well designed in order to assess anti-tumor activity as well as clinical utility of the biomarker. Classical phase II designs do not deal with this molecular heterogeneity and can lead to an erroneous conclusion in the whole population, whereas a subgroup of patients may well benefit from the new therapy. Moreover, the target population to be evaluated in a phase III trial may be incorrectly specified. Alternative approaches are proposed in the literature that make it possible to include two subgroups according to biomarker status (negative/positive) in the same study. Jones, Parashar and Tournoux et al. propose different stratified adaptive two-stage designs to identify a subgroup of interest in a heterogeneous population that could possibly benefit from the experimental treatment at the end of the first or second stage. Nevertheless, these designs are rarely used in oncology research. After introducing these stratified adaptive designs, we present an R package (ph2hetero) implementing these methods. A case study is provided to illustrate both the designs and the use of the R package. These stratified adaptive designs provide a useful alternative to classical two-stage designs and may also provide options in contexts other than biomarker studies.
Published: 2018

8. The importance of jointly analyzing treatment administration and toxicity associated with targeted therapies: a case study of regorafenib in soft tissue sarcoma patients

Author: J.-P. Delord, Thomas Brodowicz, Bastien Cabarrou, M. Longue, Jennifer Wallet, H. Roche, Thomas Filleron, Jean Marie Boher, Nicolas Penel, Institut Claudius Regaud, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université médicale de Vienne, Autriche, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), This project was supported by the CAPTOR project: ANR-11-PHUC-0001., ANR-11-PHUC-0001,CAPTOR,Cancer et Pharmacologie : Projet de Toulouse-Oncopole et de sa Région(2011), Université de Lille, LillOA, Pôle hospitalier Universitaire Cancer (PHUC) - Cancer et Pharmacologie : Projet de Toulouse-Oncopole et de sa Région - - CAPTOR2011 - ANR-11-PHUC-0001 - PHUC - VALID, Unité de Biostatistiques [Toulouse] ( Institut Claudius Regaud / IUCT-O), Institut Universitaire du Cancer Toulouse - Oncopôle (IUCT)-Institut Claudius Regaud, Service de biostatistiques [CHU Lille] (Centre Oscar Lambret), Comprehensive Cancer Center [Vienna, Austria], Institute of Cancer Research [Vienna, Austria]-Medizinische Universität Wien = Medical University of Vienna, Département d'Oncologie Médicale [CHU Toulouse] (IUCT Oncopole - Institut Universitaire du Cancer), Centre hospitalier universitaire de Toulouse - CHU Toulouse-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Biostatistiques [Institut Paoli-Calmettes] (Département de la Recherche clinique et de l'Innovation), Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'oncologie médicale (CHRU Lille), ANR-11-PHUC-0001/11-PHUC-0001,CAPTOR,Cancer et Pharmacologie : Projet de Toulouse-Oncopole et de sa Région(2011), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, CHU Lille, Université de Lille, METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694, Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], and Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
Subjects: 0301 basic medicine, Pyridines, medicine.medical_treatment, [SDV]Life Sciences [q-bio], toxicity analysis, Targeted therapy, law.invention, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Molecular Targeted Therapy, Soft tissue sarcoma, Sarcoma, Hematology, Prognosis, targeted therapy, 3. Good health, Survival Rate, [SDV] Life Sciences [q-bio], Oncology, 030220 oncology & carcinogenesis, France, Mucositis, medicine.medical_specialty, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Drug-Related Side Effects and Adverse Reactions, prevalence, 03 medical and health sciences, Double-Blind Method, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Internal medicine, Regorafenib, medicine, dose adjustment, Humans, Adverse effect, Survival rate, Stomatitis, business.industry, Phenylurea Compounds, medicine.disease, Clinical trial, 030104 developmental biology, chemistry, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Follow-Up Studies
Abstract: International audience; Background: Different methods have been proposed to analyze adverse events (AEs) associated with targeted therapies. While these AEs lead to dose adjustments for many patients, conventional reporting methods do not take drug administration into consideration. This paper underlines the importance of jointly reporting AEs and drug administration using prevalence, and proposes a complementary approach to reporting. Patients and methods: The prevalence method estimates the probability of progression-free patients being in a particular health state (state 1: AEs with full dose; state 2: AEs with reduced dose; state 3: no AEs with reduced dose) at different time points. To take into account the impact of dose adjustments on efficacy, the weighted prevalence method can be used by assigning utility weights to the different health states. The benefit of these methods was illustrated using data from a phase II trial of regorafenib. Results: Only 4.6% of progression-free patients developed mucositis/stomatitis (grade 2) at 3 months. The prevalence of patients not experiencing this AE but whose dose was reduced or treatment interrupted was 58.1%. The weighted prevalence of the regorafenib toxicity profile and dose reduction was higher in the control arm. Conclusion: This case study confirms the importance of jointly analyzing AEs and drug administration. The weighted prevalence approach is an average score that incorporates the dimension of drug administration into AE assessment. This can be helpful for regulatory agencies as well as for clinicians to evaluate the benefit-risk ratio of therapies in their treatment choice. Clinical trial: NCT01900743.
Published: 2018

9. Glucose dysregulation in Parkinson's disease: Too much glucose or not enough insulin?

Author: Frédéric Dutheil, Yves Boirie, Ana Marques, Elodie Durand, Maria Livia Fantini, Franck Durif, Isabelle Rieu, Aurélien Mulliez, Groupe de sociologie politique et morale (GSPM), École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Psychologie Sociale et Cognitive - Clermont Auvergne (LAPSCO), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), École d’Orthoptie - Clermont-Ferrand (EO - UdA), CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), CHU Clermont-Ferrand, Unité de Biostatistiques, Délégation Recherche Clinique & Innovation, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Groupe de sociologie politique et morale ( GSPM ), École des hautes études en sciences sociales ( EHESS ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Psychologie Sociale et Cognitive - Clermont Auvergne ( LAPSCO ), Université Clermont Auvergne ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), École d’Orthoptie - Clermont-Ferrand ( EO - UdA ), CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I ( UdA ), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne ( NPsy-Sydo ), CHU Clermont-Ferrand-Université Clermont Auvergne ( UCA ), Unité de Nutrition Humaine ( UNH ), Institut National de la Recherche Agronomique ( INRA ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Clermont Université, Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0301 basic medicine, Blood Glucose, Male, Parkinson's disease, Dopamine, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Administration, Oral, Neurodegenerative disease, [ SDV.NEU.SC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 0302 clinical medicine, Insulin, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Diabetes, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Parkinson Disease, Middle Aged, 3. Good health, Neurology, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [ SCCO.NEUR ] Cognitive science/Neuroscience, Female, medicine.symptom, medicine.drug, medicine.medical_specialty, [ SDV.NEU.PC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, 03 medical and health sciences, Internal medicine, Diabetes mellitus, medicine, Humans, Aged, Glucose Metabolism Disorders, Retrospective Studies, Autonomous nervous system, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Dysautonomia, Metabolism, Glucose Tolerance Test, medicine.disease, 030104 developmental biology, Endocrinology, Autonomic Nervous System Diseases, Blood sugar regulation, Neurology (clinical), Geriatrics and Gerontology, business, Body mass index, 030217 neurology & neurosurgery
Abstract: Objective To detect changes in glucose regulation in moderate to advanced Parkinson's disease (PD) patients in response to oral glucose intake. Methods Blood glucose and insulin kinetics during a 75-g Oral Glucose Tolerance Test (OGTT) were compared between 50 PD patients and 50 healthy controls (CT) matched for body mass index (BMI), age and sex. Potential relationships between changes in glucose kinetics and clinical parameters were analyzed including Parkinson's disease severity and autonomic function using SCOPA-AUT (Scales for Outcomes in Parkinson's disease, Autonomic dysfunction). Results Blood glucose was significantly higher at T90 (p = 0.04) and T150 (p = 0.01) in PD patients compared to healthy matched controls. Moreover, the total area under time curve (AUC) for the blood glucose levels was significantly higher in PD patients compared to healthy controls (1187 ± 229 vs 1101 ± 201 mmol min.l-1; p = 0.05). Simultaneously, no significant increase of insulin levels was observed in PD patients compared to controls. Higher blood glucose levels were associated with higher BMI (p Conclusion Glucose control is impaired in moderate to advanced non-diabetic PD patients, due to impaired adaptive insulin response which may be a novel non-motor consequence of PD associated dysautonomia.
Published: 2018

10. Measuring the effects of in vitro mastication on bolus granulometry of shredded meat: A proposal for a new methodological procedure

Author: Anne Duconseille, Hennequin Martine, Olivier François, Peyron Marie-Agnès, Pereira Bruno, Lambert Céline, Centre de Recherche en Odontologie Clinique - Clermont Auvergne (CROC), Université Clermont Auvergne (UCA), CHU Clermont-Ferrand, Unité de Biostatistiques, Délégation Recherche Clinique & Innovation, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Centre de Recherche en Odontologie Clinique (CROC), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and French AlimaSSenS project (ANR- 14-CE20-0003)
Subjects: Glycerol, Generalized linear models, Meat, Models, Biological, Image analysis, Bolus, 03 medical and health sciences, Eating, 0302 clinical medicine, Humans, Food science, Particle Size, Mastication, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Mathematics, 2. Zero hunger, 0303 health sciences, Granulometry, food and beverages, 030206 dentistry, Biomechanical Phenomena, Deglutition, Bolus (digestion), [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Analysis, Food Science
Abstract: International audience; People with poor oral status and/or neuromuscular deficiencies avoid eating meat because of chewing and swallowing difficulties. Consequently, they expose themselves to the risk of malnutrition and sarcopenia or nutrient deficiencies. To develop a new process for meat preparation, it is necessary to understand how meat is broken down during food oral processing to become a swallowable bolus. However, it is unknown whether the initial texture of meat impacts the meat bolus granulometry. As meat particles are fibrous, making the granulometry analysis with sieving methods is difficult. As the approach of meat bolus granulometry is necessary, it is of importance to control the methodological parameters that affect the measures. This study describes a procedure that allows granulometry analysis of shredded meat before and after in vitro mastication. Meat particles were dispersed in glycerol before image analysis. Granulometry curves were then drawn using generalized linear models, particle by particle, or after applying virtual sieves. Artificial meat bolus granulometry was also analyzed by manual sieving and the different methods were compared through several characteristics, including D50. Image analysis in glycerol preserves meat particles and allows particle distribution characterization and shape descriptors analysis. This method is well adapted to shredded meat and could be performed to evaluate the mastication of meat preparations adapted for deficient mastication.
Published: 2018

11. Relation entre la violence intra-hospitalière des patients avec psychoses et la violence dans la communauté

Author: L. Stamatiadis, M. Olari, S. Lazareth, D. Gastal, S. Bleher, J. Themines, R. Oukebdane, S. Haouzir, Dominique Januel, J.-L. Terra, Dominique Campion, Jean-Pierre Olié, C.-E. Rengade, M.-F. Poirier, Bruno Millet, Sonia Dollfus, F. Kazour, Olivier Guillin, A. Gassiot, G. Levacon, P. Lebain, Mocrane Abbar, J. Bénichou, Maud Rothärmel, Service hospitalo-universitaire, centre hospitalier du Rouvray, 4, rue Paul-Eluard, 76300 Sotteville-lès-Rouen, France, Service hospitalo-universitaire de santé mentale et de thérapeutique, centre hospitalier Saint-Anne, 75014 Paris, France., Service de psychiatrie, faculté de médecine, Beyrouth, Liban., Service hospitalo-universitaire, centre hospitalier Guillaume-Régnier, 35703 Rennes, France., Unité de recherche clinique 93G03, établissement public de santé de Ville Evrard, 93330 Neuilly-sur-Marne, France., Service de psychiatrie A1, centre hospitalo-universitaire de Nîmes, 30900 Nîmes, France, Service hospitalo-universitaire, centre Esquirol, centre hospitalo-universitaire de Caen, 14003 Caen, France., Service hospitalo-universitaire, centre hospitalier du Rouvray, 4, rue Paul-Eluard, 76300 Sotteville-lès-Rouen, France., Service de psychiatrie 93G01, établissement public de santé de Ville Evrard, 93200 Saint-Denis, France., Service de psychiatrie 69G012, centre hospitalier du Vinatier, 69500 Bron, France., Unité intersectoriel de psychiatrie, centre hospitalier Sainte-Marie, 12032 Rodez, France., Service de psychiatrie A1, centre hospitalo-universitaire de Nîmes, 30900 Nîmes, France., Unité intersectoriel de psychiatrie, centre hospitalier Sainte-Marie, 12032 Rodez, France, Service de psychiatrie 93G01, établissement public de santé de Ville Evrard, 93200 Saint-Denis, France, Parcours santé systémique ( P2S ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon, Unité de biostatistiques [Rouen], CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Génétique du cancer et des maladies neuropsychiatriques ( GMFC ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Esquirol [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Parcours santé systémique (P2S), Université Claude Bernard Lyon 1 (UCBL), Unité de biostatistiques [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Arts and Humanities (miscellaneous), [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [ SDV.MHEP.PSM ] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, 16. Peace & justice, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS, 3. Good health, 030227 psychiatry
Abstract: Resume Contexte La violence est un probleme frequent dans les services de psychiatrie. Le niveau de violence du lieu de vie des patients n’a pas ete etudie comme une variable explicative de la violence intra-hospitaliere. Methode Nous avons mene une etude prospective dans 9 villes francaises tres contrastees du point de vue de leur niveau de violence. Les sujets eligibles etaient des patients hospitalises sous contrainte pour troubles psychotiques, dans une des unites de psychiatrie de chaque ville concernee. Au cours de leur hospitalisation, tout type de comportement agressif etait recueilli par l’Overt Aggression Scale (OAS). Resultats De juin 2010 a mai 2011, 95 patients ont ete inclus. Soixante-dix-neuf pour cent des patients ont montre un comportement violent au cours de leur hospitalisation. La violence des patients etait significativement liee : au sexe masculin, aux antecedents de violence agis par le patient, a l’abus de substances autre que la nicotine, a la presence d’un episode maniaque ou mixte, a l’intensite de la symptomatologie mesuree par la Brief Psychiatric Rating Scale (BPRS), au degre d’insight et au taux de violence a la personne des villes correspondant au secteur du patient. Dans une analyse multivariee, les seuls facteurs significativement lies a la violence des patients etaient l’abus de substance, la severite des symptomes psychotiques et le taux de violence des villes. Conclusion Cette etude suggere que la violence dans l’environnement de vie des patients est associee a une augmentation du risque de passage a l’acte violent au cours de leur hospitalisation.
Published: 2017

12. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial

Author: Catherine Prost-Squarcioni, Pierre Vabres, Philippe Bernard, Maud Maho-Vaillant, Estelle Houivet, Laurent Misery, Saskia Ingen-Housz-Oro, Sébastien Debarbieux, Alain Dupuy, Marie-Laure Golinski, P. Musette, Jean-David Bouaziz, Sophie Duvert-Lehembre, Pascal Joly, Laurent Machet, Nicolas Dupin, Denis Jullien, Frédéric Caux, Marie Beylot-Barry, Sébastien Calbo, Vivien Hébert, Martine Avenel-Audran, Bruno Sassolas, Carle Paul, Olivier Dereure, Gaëlle Quéreux, Emmanuel Delaporte, Jacques Benichou, Catherine Picard-Dahan, Nathalie Beneton, Bruno Labeille, Marie-Aleth Richard, Michel D'Incan, Christophe Bedane, Frédérique Caillot, Thomas Vermeulin, Marina Alexandre, Service de Dermatologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre de référence sur les maladies bulleuses autoimmunes (Rouen), CHU Rouen, Service de dermatologie [Paris], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de biostatistiques [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), University Hospital of St-Etienne, Department of Dermatology, Service de Dermatologie, Hôpital Bichat, AP-HP, Service de dermatologie (CHU de Toulouse), CHU Toulouse [Toulouse], Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Service de Dermatologie [AP-HP Hôpital Saint Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Service de dermatologie (CHU de Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Henri Mondor, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Equipe GAD (LNC - U1231), 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-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, Service de dermatologie (CHRU de Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Dermatologie [Rennes] = Dermatology [Rennes], CHU Pontchaillou [Rennes], Service de Dermatologie, Centre Hospitalier Sud, Hospices Civils, Lyon, Département de Dermatologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de Dermatologie et Oncologie Cutanée [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Dermatologie [CHU Limoges], CHU Limoges, Service de dermatologie [CH Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Service de dermatologie (Dermato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Dermatologie, Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de dermatologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Service d'informatique biomédicale [Rouen], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Unité de biostatistiques [Rouen], Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-AP-HP Hôpital Saint-Louis, Service de Dermatologie [Rennes], Service de dermatologie et oncologie cutanée (CHU Clermont Ferrand), CHRU Clermont Ferrand, Service de dermatologie (CH Le Mans), Hôpital Trousseau (Tours), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Centre Hospitalier Universitaire de Toulouse - CHU Toulouse (FRANCE), 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 ), Université Paris Diderot - Paris 7 ( UPD7 ) -AP-HP Hôpital Saint-Louis, Centre Hospitalier Universitaire de Reims ( CHU Reims ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), 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 ) -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 ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Université de Nantes ( UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre Hospitalier Universitaire d'Angers, CH Le Mans, Service de dermatologie ( Dermato - BREST ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Département de Médecine Interne et Pneumologie [Brest] ( DMIP - Brest ), Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Dermatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Service Dermatologie [CHU Toulouse], Pôle Clinique des Voies respiratoires [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and CHU Henri Mondor [Créteil]
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Prednisolone, Follow-Up, Vulgaris, law.invention, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Prednisone, law, Internal medicine, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, Corticosteroids, Disease, Prospective Studies, Prospective cohort study, Adjuvant, Aged, business.industry, Standard treatment, General Medicine, Middle Aged, Mycophenolate-Mofetil, medicine.disease, 3. Good health, Surgery, Pemphigus, Regimen, 030104 developmental biology, Treatment Outcome, Combination, Rituximab, Female, Therapy, business, Single-Cycle, Intensity Score Absis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: IF 44.002; International audience; Background High doses of corticosteroids are considered the standard treatment for pemphigus. Because long-term corticosteroid treatment can cause severe and even life-threatening side-effects in patients with this disease, we assessed whether first-line use of rituximab as adjuvant therapy could improve the proportion of patients achieving complete remission off-therapy, compared with corticosteroid treatment alone, while decreasing treatment side-effects of corticosteroids.Methods We did a prospective, multicentre, parallel-group, open-label, randomised trial in 25 dermatology hospital departments in France (Ritux 3). Eligible participants were patients with newly diagnosed pemphigus aged 18-80 years being treated for the first time (not at the time of a relapse). We randomly assigned participants (1: 1) to receive either oral prednisone alone, 1.0 or 1.5 mg/kg per day tapered over 12 or 18 months (prednisone alone group), or 1000 mg of intravenous rituximab on days 0 and 14, and 500 mg at months 12 and 18, combined with a short-term prednisone regimen, 0.5 or 1.0 mg/kg per day tapered over 3 or 6 months (rituximab plus short-term prednisone group). Follow-up was for 3 years (study visits were scheduled weekly during the first month of the study, then monthly until month 24, then an additional visit at month 36). Treatment was assigned through central computer-generated randomisation, with stratification according to disease-severity (severe or moderate, based on Harman's criteria). The primary endpoint was the proportion of patients who achieved complete remission off-therapy at month 24 (intention-to-treat analysis). This study is registered with ClinicalTrials.gov, number NCT00784589.Findings Between May 10, 2010, and Dec 7, 2012, we enrolled 91 patients and randomly assigned 90 to treatment (90 were analysed; 1 patient withdrew consent before the random assignment). At month 24, 41 (89%) of 46 patients assigned to rituximab plus short-term prednisone were in complete remission off-therapy versus 15 (34%) of 44 assigned to prednisone alone (absolute difference 55 percentage points, 95% CI 38.4-71.7; p
Published: 2017

13. Glucocorticoid-sparing effect of first-year anti-TNFα treatment in rheumatoid arthritis (CORPUS Cohort)

Author: Duquenne, Carole, Wendling, Daniel, Sibilia, Jean, Job-Deslandre, Chantal, Guillevin, Loic, Benichou, Jacques, Flipo, René Marc, Guillemin, Francis, Saraux, Alain, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Rhumatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Physiopathologie des arthrites, Université Louis Pasteur - Strasbourg I, Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de biostatistiques [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de rhumatologie[Lille], Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Orange Labs [Lannion], France Télécom, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Rhumatologie ( CHU - BREST - Rhumato ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Service de Rhumatologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Unité de biostatistiques [Rouen], CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Hôpital Roger Salengro-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Lymphocyte B et Auto-immunité ( LBAI ), Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Michel, Geneviève
Subjects: Adult, Male, [SDV.IMM] Life Sciences [q-bio]/Immunology, Tumor Necrosis Factor-alpha, Middle Aged, Peptides, Cyclic, Injections, Intra-Articular, Arthritis, Rheumatoid, Cohort Studies, C-Reactive Protein, Methotrexate, Rheumatoid Factor, Antirheumatic Agents, Multivariate Analysis, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Humans, Prednisone, [SDV.IMM]Life Sciences [q-bio]/Immunology, Drug Therapy, Combination, Female, Longitudinal Studies, Prospective Studies, Glucocorticoids, Aged, Autoantibodies
Abstract: Anti-TNFα agents are indicated in selected patients with rheumatoid arthritis (RA) who respond inadequately to methotrexate and particularly when glucocorticoids are mandatory. We evaluated whether a glucocorticoid-sparing effect occurred during the first year of anti-TNF-α therapy., Between 2007 and 2009, the French multicentre, longitudinal, prospective, observational, population-based CORPUS cohort included biologic-naive patients with inflammatory joint disease. Patients with active RA treated with glucocorticoids were included. Patients who received at least one anti-TNFα injection during follow-up were compared to anti-TNF-α non-users., Among the 205 patients, 76.1% were women, mean disease duration was 7.7±8.3 years, mean DAS28 was 5.2±1.3, mean follow-up was 13.1±2.8 months, and mean prednisone dose was 9.9±9.6 mg/day. The 75 (36.6%) anti-TNF-α recipients were younger, had a longer RA duration, more often tested positive for rheumatoid factor and anti-citrullinated peptide antibody, more often received previous DMARDs, received a higher methotrexate dosage, had fewer intra-articular glucocorticoid injections at baseline and were more often followed by hospital practitioners than non-recipients. Mean prednisone dosage decreased from 11.8±12.7 to 5.9±9.7 mg/day in recipients and from 8.7±7.1 to 5.0±4.4 mg/day in non-recipients. Prednisone was stopped more often among recipients (21/59, 35.6%) than among non-recipients (16/94, 17.0%) (p=0.01). By multivariate analysis, factors independently associated with lower prednisone requirements were baseline daily prednisone dosage, a CRP >10 mg/l and not to be followed by an office-based practitioner., This study showed a significantly higher glucocorticoid discontinuation rate among anti-TNF-α recipients than among non-recipients. However, the glucocorticoid-sparing effect was small and not observed by multivariate analysis.
Published: 2017

14. Diffusion-Weighted MRI is not superior to FDG-PET/CT for the detection of neck recurrence in well-differentiated thyroid carcinoma

Author: Joseph Le Cloirec, Agathe Edet-Sanson, Anne-Sophie Bertrand, Francoise Callonnec, Charlotte Lussey-Lepoutre, Farzaneh Quieffin, Pierre Vera, Jean-François Ménard, Martin Cailleaux, Service de médecine nucléaire [Rouen], CRLCC Haute Normandie-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Normandie Université (NU), Unité de biostatistiques [CHU Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de radiologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), CRLCC Haute Normandie-CRLCC Henri Becquerel, Equipe Quantification en Imagerie Fonctionnelle ( QuantIF-LITIS ), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes ( LITIS ), Université Le Havre Normandie ( ULH ), Normandie Université ( NU ) -Normandie Université ( NU ) -Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Institut national des sciences appliquées Rouen Normandie ( INSA Rouen Normandie ), Normandie Université ( NU ) -Université Le Havre Normandie ( ULH ), Normandie Université ( NU ), Unité de biostatistiques [Rouen], CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CRLCC Henri Becquerel, Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), CHU Rouen, Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, Concordance, medicine.medical_treatment, Whole body imaging, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030218 nuclear medicine & medical imaging, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Thyroid carcinoma, Iodine Radioisotopes, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Fluorodeoxyglucose F18, Positron Emission Tomography Computed Tomography, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Whole Body Imaging, Thyroid Neoplasms, Aged, medicine.diagnostic_test, Whole-Body Scintigraphy, business.industry, Magnetic resonance imaging, Middle Aged, Diffusion Magnetic Resonance Imaging, Thyroglobulin, Female, Neoplasm Recurrence, Local, business, Nuclear medicine, Kappa, Neck, Diffusion MRI
Abstract: BACKGROUND Management of patients with well-differentiated thyroid carcinoma (WDTC) and positive thyroglobulin (Tg)/negative iodine-131 whole body scintigraphy (WBS) remains challenging. Here, we investigate the specific role of diffusion-weighted magnetic resonance imaging of the neck (DW-MRI) as compared to rhTSH stimulated FDG-PET/CT in such patients. METHODS Patients with WDTC, positive Tg/negative WBS were prospectively enrolled in the study. FDG-PET/CT and neck DW-MRI were performed on the same day after rhTSH stimulation. Neck-US was performed 24 hours after FDG-PET/CT and MRI to guide fine-needle aspiration (FNA). Patients with positive FNA underwent surgery. Patient with negative workup underwent new explorations at 6 and 18 months. RESULTS A total of 86 FDG-PET/CT and 83 DW-MRI tests were performed in 40 patients (23 females; 17 males; 52±16 years). For detection of neck recurrences, sensitivity was equivalent for FDG-PET/CT and to DW-MRI at baseline (46% vs. 43%), at 6 months (30% vs. 20%) and at 18 months (11 vs. 10%). The comparison with a non-weighted Kappa test shows significant concordance between FDG-PET/CT and DW-MRI (K=0.741±0.062; P
Published: 2017

15. Copy number variations in DCC/ 18q and ERBB2/ 17q are associated with disease-free survival in microsatellite stable colon cancer

Author: Sefrioui , France, Vermeulin , France, Blanchard , France, Chapusot , Caroline, Beaussire , Ludivine, Armengol-Debeir , Laura, Sesboué , Richard, Gangloff , Alice, Hebbar , Mohamed, Copin , Marie-Christine, Houivet , Estelle, Schwarz , Lilian, Clatot , Florian, Tuech , Jacques, Bénichou , Jacques, Martin , Laurent, Bouvier , Anne-Marie, Sabourin , Jean-Christophe, Sarafan-Vasseur , Nasrin, Frébourg , Thierry, Lepage , Côme, Michel , Pierre, Di Fiore , Frédéric, Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Hôpital Charles Nicolle [Tunis], Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Pathologie, PRES Université Lille Nord de France-Faculté de Médecine Henri Warembourg-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Charles Nicolle [Rouen], Groupe d'étude des proliférations lymphoïdes (GPL), Unité de biostatistiques [CHU Rouen], Centre Guillaume le Conquérant, Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Département d'oncologie médicale [Rouen], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Génétique du cancer et des maladies neuropsychiatriques ( GMFC ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Hépato-Gastroentérologie [Rouen], Normandie Université ( NU ) -Normandie Université ( NU ) -Hôpital Charles Nicolle [Rouen]-CHU Rouen, Unité de biostatistiques [Rouen], CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Service de Pathologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service d'oncologie médicale (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service de pathologie [CHU Lille], Département de chirurgie [Rouen], CRLCC Henri Becquerel, Service de chirurgie digestive [Rouen], Registre Bourguignon des Cancers Digestifs, Lipides - Nutrition - Cancer (U866) ( 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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -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-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service d'Oncologie Médicale, and Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen ( CLCC Henri Becquerel )
Subjects: Male, Proto-Oncogene Proteins B-raf, MESH: Colon Cancer, DNA Copy Number Variations, Receptor, ErbB-2, MESH: Chromosomal instability, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, MESH: Copy Number Variation, Loss of Heterozygosity, Receptors, Cell Surface, Polymerase Chain Reaction, Disease-Free Survival, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Humans, Prospective Studies, Neoplasm Metastasis, Aged, Proportional Hazards Models, Colon Cancer, Tumor Suppressor Proteins, Carcinoma, Middle Aged, DCC Receptor, Prognosis, Copy Number Variation, Chromosomal instability, Microstellite Stable, Phenotype, Treatment Outcome, Colonic Neoplasms, MESH: Disease-Free Survival, Female, MESH: Microstellite Stable, Neoplasm Recurrence, Local, Microsatellite Repeats
Abstract: IF 5.531; International audience; We conducted a prospective study to assess the prognostic impact of selected copy number variations (CNVs) in stage II-III microsatellite stable (MSS) colon cancer. A total of 401 patients were included from 01/2004 to 01/2009. The CNVs in 8 selected target genes, DCC/18q, EGFR/7p, TP53/17p, BLK/8p, MYC/8q, APC/5q, ERBB2/17q, and STK6/20q, were detected using a quantitative multiplex polymerase chain reaction of short fluorescent fragment (QMPSF) method. The primary end-point was the impact of the CNVs on the 4-year disease-free survival (DFS). The recurrence rate at 4 years was 20.9%, corresponding to 14% stage II patients vs 31% stage III patients (p
Published: 2017

16. Comparative acceptability and perceived clinical utility of monitoring tools: A nationwide survey of patients with inflammatory bowel disease

Author: Guillaume Bonnaud, François Lʼhopital, Florent Gonzalez, Florian Poullenot, Mathurin Fumery, Stéphane Nancey, Veronique Michalet, Stephane Mathieu, Marc Duruy, Anca Achim, Gilles Bommelaer, Fabrice Luneau, Mathurin Flamant, Alain Thevenin, Julien P. Genes, Jérôme Filippi, Laurent Peyrin-Biroulet, David Laharie, Anthony Buisson, Emmanuelle Cruzille, Caroline Trang-Poisson, Guillaume Bouguen, Elisa Sollellis, Bruno Pereira, Maria Nachury, Benjamin Pariente, Service de Hépato-Gastro-Entérologie, CHU Clermont-Ferrand, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Département de Gastroentérologie, Private Practice, Hôpital Européen [Fondation Ambroise Paré - Marseille], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Private Practice Endocrinologist, Hôpital de l'Archet 2, Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Médical Clermont Sud, Centre Hospitalier Universitaire de Clermont-Ferrand, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), and Unité de Biostatistiques
Subjects: Adult, Male, endoscopie, medicine.medical_specialty, Visual analogue scale, medicine.medical_treatment, acceptabilité, Colonoscopy, vidéo surveillance, Inflammatory bowel disease, Capsule Endoscopy, law.invention, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Capsule endoscopy, law, colonoscopy, inflammatory bowel disease, Internal medicine, Surveys and Questionnaires, acceptability, inflammation intestinale, Immunology and Allergy, Medicine, Humans, Prospective Studies, endoscopy, Ultrasonography, Venipuncture, medicine.diagnostic_test, business.industry, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Enema, medicine.disease, Inflammatory Bowel Diseases, Prognosis, Ulcerative colitis, monitoring tools, 3. Good health, utility, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Perception, business, Biomarkers, Follow-Up Studies
Abstract: Background: Objective control of intestinal inflammation during inflammatory bowel disease (IBD) is becoming the main driver for medical treatment. However, the monitoring tools-related burden remains poorly investigated. We aimed to evaluate their comparative acceptability and utility according to patients with IBD. Methods: After a preliminary phase, the final questionnaire encompassing self-administered and physician questionnaires was prospectively and consecutively submitted to 916 patients with IBD from 20 public and private centers. Acceptability and utility visual analog scales (VAS) were expressed as median with interquartile range. Results: Regarding the group of patients with Crohn's disease (n = 618), venipuncture (VAS = 9.3 [8.8-9.7]) and ultrasonography (VAS = 9.3 [8.7-9.7]) were the most acceptable tools (P < 0.0001, for each comparison), whereas rectosigmoidoscopy was the least acceptable tool (VAS = 4.4 [1.2-7.3]) (P < 0.0001, for each comparison). Wireless capsule endoscopy (VAS = 8.5 [5.2-9.3]), magnetic resonance enterocolonography (VAS = 8.0 [5.0-9.2]), and stools collection (VAS = 7.7 [4.6-9.3]) were more acceptable than colonoscopy (VAS = 6.7 [4.3-8.9]) (P < 0.0001, for each comparison). The acceptability was assessed in 298 patients with ulcerative colitis for venipuncture (VAS = 9.4 [8.8-9.7]), stools collection (VAS = 8.1 [5.7-9.4]), colonoscopy (VAS = 7.5 [4.7-9.2]), and rectosigmoidoscopy (VAS = 6.7 [2.8-9.1]); (P < 0.001 for each comparison). All monitoring tools were considered as highly useful by patients with IBD. Decreased acceptability was related to embarrassment for the collection/transport of stools (60.7%), bowel cleansing (76.3%) for colonoscopy, abdominal discomfort (51.3%) and rectal enema (36.6%) for rectosigmoidoscopy, bowel distension (48.3%) for magnetic resonance enterocolonography, and potential capsule retention (21.4%) for wireless capsule endoscopy. Conclusions: Among the IBD monitoring tools, endoscopy demonstrated the lowest acceptability supporting the development of alternative modalities. Patients' information and examination conditions should be improved to ensure proper monitoring adherence.
Published: 2017

17. Determinants of Resting Energy Expenditure in Very Old Nursing Home Residents

Author: Lahaye, Clément, Derumeaux-Burel, H., Guillet, C., Pereira, B., Boirie, Y., Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), CHU Clermont-Ferrand, Service Médecine Interne et immunologie clinique [CHU Toulouse], Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), and CHU Clermont-Ferrand-CHU Clermont-Ferrand
Subjects: Male, Resting energy expenditure, body composition, Nutrition and Dietetics, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, aging, Medicine (miscellaneous), Calorimetry, Indirect, malnutrition, Body Mass Index, Nursing Homes, Cross-Sectional Studies, inflammatory status, Humans, Female, Basal Metabolism, Geriatrics and Gerontology, Energy Metabolism, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; Objectives This study aimed to measure resting energy expenditure (REE) in institutionalized old persons and to determine factors possibly related to change in REE as a basis for estimating energy requirements. Design and Settings A monocentric cross-sectional study was conducted. Statistical approaches were conducted to determine independent factors associated with REE. Various published predictive equations of REE were compared to our population. Participants 72 residents of a nursing home, mostly women (80.5%) aged 87.4 +/- 6.6 years were included. Measurements REE (indirect calorimetry), body composition (bio-impedance analysis), biological and anthropometric data were collected. Results Mean REE was 1006 +/- 181 kcal/d and was higher in men than in (1227 +/- 195 vs. 953 +/- 131 kcal/d, p 25 mg/l). Significant differences (p
Published: 2022

18. Efficacy of Thin and Ultrathin Descemet Stripping Automated Endothelial Keratoplasty and Influence of Graft Thickness on Postoperative Outcomes: Systematic Review and Meta-analysis

Author: Lauren Béal, Valentin Navel, Bruno Pereira, Florent Magnier, Stephanie L. Watson, Julien S. Baker, Frédéric Chiambaretta, Frédéric Dutheil, Service d'Ophtalmologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), The University of Sydney, Sydney Eye Hospital, Hong Kong Baptist University (HKBU), Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), and Service Santé Travail Environnement [CHU Clermont-Ferrand]
Subjects: Graft Rejection, Ophthalmology, Endothelium, Corneal, Visual Acuity, Humans, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Refraction, Ocular, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Descemet Stripping Endothelial Keratoplasty, Corneal Diseases, Retrospective Studies
Abstract: International audience; PurposeTo conduct a systematic review and meta-analysis on the efficacy of thin and ultrathin Descemet stripping automated endothelial keratoplasty (T-DSAEK and UT-DSAEK, with graft thickness 100 μm induced a hyperopic shift. Metaregressions did not demonstrate differences between the 3 groups (100 μm.
Published: 2022

19. Impact of medication reconciliation at discharge on continuity of patient care in France

Author: Gilles Bommelaer, Sarah Talavera-Pons, Armand Abergel, Mélanie Van Hollebeke, Valérie Sautou, Anne Boyer, Aurélien Mulliez, Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Institut de Chimie de Clermont-Ferrand (ICCF), SIGMA Clermont (SIGMA Clermont)-Institut de Chimie du CNRS (INC)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA), Service d'Hépatogastroentérologie, CHU Saint-Eloi, Université de Clermont-Ferrand, Université Grenoble Alpes (UGA), CHU Clermont-Ferrand, Unité de Biostatistiques, Délégation Recherche Clinique & Innovation, Institut de Chimie de Clermont-Ferrand - Clermont Auvergne (ICCF), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Knowledge Information and Web Intelligence (KIWI), Department of Complex Systems, Artificial Intelligence & Robotics (LORIA - AIS), Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Hôpital Saint Eloi (CHRU Montpellier), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Male, medicine.medical_specialty, Prescription Drugs, Pharmaceutical Science, Pharmacy, Pilot Projects, Community Pharmacy Services, Toxicology, Pharmacists, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Medication Reconciliation, Professional Role, Health care, Chi-square test, Medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Prospective Studies, Medical prescription, Hospital pharmacy, Prospective cohort study, Hospital discharge, Aged, Pharmacology, business.industry, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Continuity of Patient Care, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Patient Discharge, 3. Good health, Family medicine, Continuity of treatment, Female, Medical emergency, France, business, Pharmacy Service, Hospital, Seamless care, Community pharmacy, Medication list
Abstract: International audience; Background Care transitions from hospital to community have been identified as risk points for the continuity of patient care. Without upstream information, the community pharmacist (CP) cannot ensure error-free drug dispensing. A hospital-to-community records transmission process would enable CPs to guarantee that all prescription drugs are ready to pick up at hospital discharge, and to improve their responses to patient health inquiries. Objective To evaluate the impact of a hospital-to-CP medication records scheme on post-discharge continuity of patient treatment. Setting A University Hospital Digestive Surgery Department. Method Prospective, single-center, randomized pilot study. Eligible adult Digestive Surgery department patients discharged home over a period of 4 months were included. The medication reconciliation procedure was the same in both arms of the study. For patients included in the intervention group, CPs were sent the discharge prescription, patient medication list, and clinical and biological data required for drug dispensing. At 7 ± 2 days post-discharge, the CPs were surveyed by questionnaire. Seamlessness of drug continuity, use of the discharge medication form, and CP satisfaction with the scheme were assessed. Main outcome measures Prevalence of medication shortages, i.e. CPs unable to supply the appropriate drugs at discharge, and CP satisfaction levels, analyzed using Chi squared test. Results 124 patients were included. Of 124 CPs surveyed, 104 returned a completed questionnaire. Analysis found medication shortage in 10 control-group patients and one intervention-group patient (p < 0.005), non-availability of the full prescription in 24 % of control-group patients and 6 % of intervention-group patients (p < 0.013). In terms of CP satisfaction, 96 % of the intervention-group CPs stated that they were satisfied with the new hospital-to-community liaison initiative, while just 24 % of control-group CPs were satisfied with the current level of hospital-to-community liaison. Mean hospital pharmacist time input required for this initiative was an estimated 21 min for the control group versus 35 min for the intervention group. Conclusion The results provide a strong rationale for embedding the process longer-term and extending it out to other healthcare services. A pre-project study is needed to define which service departments and patients groups should be given priority for this process initiative.
Published: 2016

20. Value of ultrasonography as a marker of early response to abatacept in patients with rheumatoid arthritis and an inadequate response to methotrexate: results from the APPRAISE study

Author: Nguyen, Minh Vu Chuong, Romand, Xavier, Trocme, Candice, Courtier, Anaïs, Marotte, Hubert, Thomas, Thierry, Miossec, Pierre, Tebib, Jacques, Grange, Laurent, Toussaint, Bertrand, Gaudin, Philippe, Nourisson, Cynthia, Soubrier, Martin, Mulliez, Aurelien, Baillet, Athan, Bardin, Thomas, Combe, Bernard, Dougados, Maxime, Flipo, René-Marc, Ravaud, Philippe, Tournadre, Anne, Derambure, C., Dzangue-Tchoupou, G., Bérard, C., Vergne, N., Hiron, M., D’Agostino, M., Musette, P., Lequerré, Thierry, Ruyssen-Witrand, Adeline, Degboé, Yannick, Cantagrel, Alain, Nigon, D., Lukas, C., Scaramuzzino, S, Allanore, Y., Schaeverbeke, Thierry, Morel, J., Sibilia, Jean, Cambon-Thomsen, A., Dieudé, P., Constantin, A, Nocturne, G., Virone, A., Ng, Wan-Fai, Le Guern, V., Hachulla, E., Cornec, D., Daien, C., Bienvenu, B., Marcelli, C., Wendling, D., Amoura, Z., Dhote, R., Lavigne, C., Fior, R., Gottenberg, Jacques-Eric, Seror, R., Mariette, Xavier, Eble, V., Legallicier, B., Joly, P., Caron, F., Tamion, F., Ducrotté, P., Lévesque, H., Ménard, J.-F., Jouen, F., Guerrot, D., Marié, I., D'Agostino, Maria-Antonietta, Wakefield, Richard, Berner-Hammer, Hilde, Vittecoq, Olivier, Filippou, Georgios, Bálint, Péter, Möller, Ingrid, Iagnocco, Annamaria, Naredo, Esperanza, Ostergaard, Mikkel, Boers, Maarten, Gaillez, Corine, Van Holder, Karina, Le Bars, Manuela, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Groupe de Recherche et d'Etude du Processus Inflammatoire (GREPI), Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de Rhumatologie [Saint-Etienne], Hôpital de Bellevue-CHU Saint-Etienne, Service d'Endocrinologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Department of Immunogenomics, Mixed Unit HCL-BioMerieux, Hopital E. Herriot, Hospices Civils de Lyon (HCL), Service de Rhumatologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Service de rhumatologie, CHU Clermont-Ferrand, Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Lapeyronie [Montpellier] (CHU), Service de rhumatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Unité de Nutrition Humaine (UNH), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), 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), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Laboratoire de Mathématiques Raphaël Salem (LMRS), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), CHU Toulouse [Toulouse], Service de rhumatologie et réadaptation fonctionelle, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Hôpital Purpan [Toulouse], Centre de rhumatologie, CHU Purpan, 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 Bordeaux [Bordeaux], Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], 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, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Institute of Cellular Medicine [Newcastle], Newcastle University [Newcastle], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Rhumatologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Avicenne [AP-HP], Hôpital Antoine Béclère, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immuno-Rhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), CHU Le Kremlin-Bicêtre (Rheumatology Department), Department of Rheumatology, Service de Médecine Interne [CHU Rouen], Service de Néphrologie [Rouen], Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Unité de biostatistiques [CHU Rouen], Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Service de Dermatologie [Rouen], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Academic Unit of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, Chapel Allerton Hospital, Rheumatology Unit [Siena], National Institute of Rheumatology and Physiotherapy, Instituto Poal de Reumatologia, Barcelona, Università degli studi di Torino (UNITO), Fundación Jiménez Díaz, Fundacion Jimenez Diaz [Madrid] (FJD), Center for Rheumatology and Spine Diseases, Copenhagen (Center for Rheumatology and Spine Diseases), VU University Medical Center [Amsterdam], Epidemiology and Data Science, Rheumatology, AII - Inflammatory diseases, Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Grenoble Alpes (UGA), Groupe de Recherche et d'Etudes du Processus Inflammatoire (GREPI), Université Joseph Fourier - Grenoble 1 (UJF), 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), CHU Saint-Etienne-Hôpital de Bellevue, Délégation à la recherche clinique et aux innovations (DRCI), CHU de Clermont-Ferrand, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière, CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Service de rhumatologie [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, CHU Cochin [AP-HP], Service de Rhumatologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Hôpital avicenne, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Avicenne, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine Interne [Rouen], Service d'Hépato-Gastroentérologie [Rouen], Unité de biostatistiques [Rouen], Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, fundacion Jimenez Diaz, VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, 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), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM), Università degli studi di Torino = University of Turin (UNITO), Service de Rhumatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Rhumatologie [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Hôpital Charles Nicolle [Rouen], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Laboratoire de recherche européen pour la polyarthrite rhumatoïde (GenHotel - EA 3886), Université d'Évry-Val-d'Essonne (UEVE), and Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne
Subjects: Male, Genetics and Molecular Biology (all), Settore MED/16 - REUMATOLOGIA, [SDV]Life Sciences [q-bio], DMARDs (biologic), Severity of Illness Index, Biochemistry, Arthritis, Rheumatoid, 0302 clinical medicine, Disease Activity, Rheumatoid Arthritis, Ultrasonography, Rheumatology, Immunology, Biochemistry, Genetics and Molecular Biology (all), Immunology and Allergy, Rheumatoid, 030212 general & internal medicine, Prospective Studies, skin and connective tissue diseases, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Synovitis, biology, Doppler, Middle Aged, 3. Good health, Europe, Treatment Outcome, Rheumatoid arthritis, Antirheumatic Agents, Combination, [SDV.IMM]Life Sciences [q-bio]/Immunology, Drug Therapy, Combination, Female, medicine.symptom, medicine.drug, musculoskeletal diseases, Adult, medicine.medical_specialty, General Biochemistry, Genetics and Molecular Biology, Abatacept, 03 medical and health sciences, Drug Therapy, Predictive Value of Tests, Internal medicine, medicine, Humans, Aged, 030203 arthritis & rheumatology, business.industry, Arthritis, C-reactive protein, Ultrasonography, Doppler, Joint effusion, Clinical and Epidemiological Research, medicine.disease, Methotrexate, biology.protein, Physical therapy, Joints, business, Rheumatism, Biomarkers
Abstract: Objectives To study the responsiveness of a combined power Doppler and greyscale ultrasound (PDUS) score for assessing synovitis in biologic-naive patients with rheumatoid arthritis (RA) starting abatacept plus methotrexate (MTX). Methods In this open-label, multicentre, single-arm study, patients with RA (MTX inadequate responders) received intravenous abatacept (∼10 mg/kg) plus MTX for 24 weeks. A composite PDUS synovitis score, developed by the Outcome Measures in Rheumatology–European League Against Rheumatism (OMERACT–EULAR)-Ultrasound Task Force, was used to evaluate individual joints. The maximal score of each joint was added into a Global OMERACT–EULAR Synovitis Score (GLOESS) for bilateral metacarpophalangeal joints (MCPs) 2–5 (primary objective). The value of GLOESS containing other joint sets was explored, along with clinical efficacy. Results Eighty-nine patients completed the 24-week treatment period. The earliest PDUS sign of improvement in synovitis was at week 1 (mean change in GLOESS (MCPs 2–5): −0.7 (95% CIs −1.2 to −0.1)), with continuous improvement to week 24. Early improvement was observed in the component scores (power Doppler signal at week 1, synovial hyperplasia at week 2, joint effusion at week 4). Comparable changes were observed for 22 paired joints and minimal joint subsets. Mean Disease Activity Score 28 (C reactive protein) was significantly reduced from weeks 1 to 24, reaching clinical meaningful improvement (change ≥1.2) at week 8. Conclusions In this first international prospective study, the composite PDUS score is responsive to abatacept. GLOESS demonstrated the rapid onset of action of abatacept, regardless of the number of joints examined. Ultrasound is an objective tool to monitor patients with RA under treatment. Trial registration number NCT00767325.
Published: 2016

21. Calculation of cut-off values based on the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Pemphigus Disease Area Index (PDAI) pemphigus scoring systems for defining moderate, significant and extensive types of pemphigus

Author: Boulard, C., Duvert Lehembre, S., Picard-Dahan, C., Kern, J.S., Zambruno, G., Feliciani, C., Marinovic, B., Vabres, P., Borradori, L., Prost-Squarcioni, C., Labeille, B., Richard, M.A., Ingen-Housz-Oro, S., Houivet, E., Werth, V.P., Murrell, D.F., Hertl, M., Bénichou, J., Joly, P., Service de Dermatologie [Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dermatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de dermatologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dermatologie, vénéreologie et cancérologie cutanée [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de dermatologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Unité de biostatistiques [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Pharmacoepidemiologie et évaluation de l'impact des produits de santé sur les populations, Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie (UNIROUEN), Hôpital Charles Nicolle [Rouen]-CHU Rouen, CHU Saint-Etienne, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie (UNIROUEN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Unité de biostatistiques [Rouen]
Subjects: integumentary system, skin and connective tissue diseases, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience; BACKGROUND:Two pemphigus severity scores, Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Pemphigus Disease Area Index (PDAI), have been proposed to provide an objective measure of disease activity. However, the use of these scores in clinical practice is limited by the absence of cut-off values that allow differentiation between moderate, significant and extensive types of pemphigus.OBJECTIVES:To calculate cut-off values defining moderate, significant and extensive pemphigus based on the ABSIS and PDAI scores.METHODS:In 31 dermatology departments in six countries, consecutive patients with newly diagnosed pemphigus were assessed for pemphigus severity, using ABSIS, PDAI, Physician's Global Assessment (PGA) and Dermatology Life Quality Index (DLQI) scores. Cut-off values defining moderate, significant and extensive subgroups were calculated based on the 25th and 75th percentiles of the ABSIS and PDAI scores. The median ABSIS, PDAI, PGA and DLQI scores of the three severity subgroups were compared in order to validate these subgroups.RESULTS:Ninety-six patients with pemphigus vulgaris (n = 77) or pemphigus foliaceus (n = 19) were included. The median PDAI activity and ABSIS total scores were 27·5 (range 3-84) and 34·8 points (range 0·5-90·5), respectively. The respective cut-off values corresponding to the first and third quartiles of the scores were 15 and 45 for the PDAI, and 17 and 53 for ABSIS. The moderate, significant and extensive subgroups were thus defined, and had distinguishing median ABSIS (P < 0·001), PDAI (P < 0·001), PGA (P < 0·001) and DLQI (P = 0·03) scores.CONCLUSIONS:This study suggests cut-off values of 15 and 45 for PDAI and 17 and 53 for ABSIS, to distinguish moderate, significant and extensive pemphigus forms. Identifying these pemphigus activity subgroups should help physicians to classify and manage patients with pemphigus.
Published: 2016

22. Monitoring of Epstein-Barr virus (EBV)/cytomegalovirus (CMV)/varicella-zoster virus (VZV) load in patients receiving tocilizumab for rheumatoid arthritis

Author: Cécile Henquell, Cinthya Nourisson, Zuzana Tatar, Cindy Mourgues, Martin Soubrier, Marion Couderc, Anne Tournadre, Bruno Pereira, CHU Clermont-Ferrand, Département rhumatologie, Unité de Biostatistiques, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Service de rhumatologie [Clermont-Ferrand], CHU Clermont-Ferrand-Hôpital Gabriel Montpied, service rhumatologie, Centre Hospitalier Universitaire de Clermont-Ferrand, Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], and Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA)
Subjects: Adult, Male, 0301 basic medicine, Herpesvirus 3, Human, Herpesvirus 4, Human, Congenital cytomegalovirus infection, Cytomegalovirus, Antibodies, Monoclonal, Humanized, medicine.disease_cause, Risk Assessment, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Virus, Arthritis, Rheumatoid, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tocilizumab, Rheumatology, medicine, Humans, Prospective Studies, ComputingMilieux_MISCELLANEOUS, Aged, 030203 arthritis & rheumatology, business.industry, virus diseases, Middle Aged, Viral Load, Prognosis, medicine.disease, Epstein–Barr virus, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Immunosurveillance, Treatment Outcome, 030104 developmental biology, chemistry, Rheumatoid arthritis, Immunology, Female, Methotrexate, business, Viral load, medicine.drug
Abstract: Introduction IL-6 is involved in viral immunosurveillance. We studied the effect of tocilizumab (TCZ) on the evolution in viral load (VL) for the Epstein-Barr virus (EBV), cytomegalovirus (CMV) and varicella-zoster virus (VZV) in patients with rheumatoid arthritis (RA). Methods EBV, CMV and VZV loads were prospectively determined in whole blood of 22 RA patients at TCZ initiation and during treatment follow-up. A difference of 0.5 log10 or of threefold copies/mL between two VL was considered significant. Results There were 20 (91%) women, (mean age of 57.8 ± 11.2 years, mean disease duration 11.3 ± 9.7 years) with 16 (73%) seropositive and 16 (73%) erosive patients. TCZ was administered alone for 8 patients (36.7%) or in combination with methotrexate for 11 patients (50%). At baseline, the EBV VL was positive in 8 patients with a mean VL value of 1777.2 ± 3518.3 (3.5 ± 0.4 log10) copies/mL. Only one patient had a positive CMV VL with 2337 copies/mL (3.4 log10). The VZV VL was negative in all patients. After 9.2 ± 4.8 months, EBV VL became negative in 6 of 8 patients (P = 0.01) and did not significantly vary in the remaining 2 patients. CMV VL became also negative. No VL (EBV, CMV, VZV) became positive. A positive EBV VL did not correlate with disease activity or with inflammatory biomarkers (ESR and CRP). Conclusion TCZ does not seem to increase the VL of EBV, CMV or VZV. Studies involving larger patient populations are necessary.
Published: 2016

23. Pediatric-Like Acute Lymphoblastic Leukemia Therapy in Adults With Lymphoblastic Lymphoma: The GRAALL-LYSA LL03 Study

Author: Patrice Chevallier, Carlos Graux, Vahid Asnafi, Anne Moreau, Thomas Vermeulin, Jacques Benichou, Gilles Salles, Stephanie Seris, Josette Brière, Norbert Ifrah, Aline Tanguy-Schmidt, Stéphane Leprêtre, Elizabeth Macintyre, Marie-Christine Béné, Jean-Michel Picquenot, Aurore Touzart, Serge Bologna, Reda Bouabdallah, Valérie Tallon-Simon, Françoise Huguet, Emmanuel Raffoux, Thierry Lamy, Hervé Dombret, Groupe d'étude des proliférations lymphoïdes ( GPL ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Necker Enfants-Malades (INEM) ( INEM - UM 111 (UMR 8253 / U1151) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Charles Nicolle [Tunis], Pharmacoepidemiologie et évaluation de l'impact des produits de santé sur les populations, Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie ( UNIROUEN ), HEMATOLOGIE, CRLCC Henri Becquerel, Service d'Hématologie Clinique [Nantes], Hôpital Hôtel Dieu-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers, Laboratoire de Biologie Moléculaire de la Cellule ( LBMC ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'hématologie clinique, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou, Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes ( CHU Nantes ), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre Hospitalier Universitaire de Purpan ( CHU Purpan ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Département d'Hematologie, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Cliniques Universitaires UCL de Mont-Godinne, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), The study was supported by a grant from the French Ministry of Health (Projet Hospitalier de Recherche Clinique of France [PHRC 2003 No. 13-2]). The Macintyre laboratory was supported by the Fondation de France, the Association de Recherche sur le Cancer, Cent pour Sang la Vie, and the Société Française des Cancers de l’Enfant. CHUGAI PHARMA France provided technical and financialsupport., Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), 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), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Nantes (CHU Nantes), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Unité de biostatistiques [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Lymphocyte et cancer, IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie (UNIROUEN), Hôpital Hôtel Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Unité de biostatistiques [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Centre Hospitalier Universitaire de Purpan (CHU Purpan), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire d'Angers ( CHU Angers ), PRES Université Nantes Angers Le Mans ( UNAM ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Université Toulouse III - Paul Sabatier ( UPS ), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], IFR105-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Bernardo, Elizabeth
Subjects: Male, Cancer Research, F-Box-WD Repeat-Containing Protein 7, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Phases of clinical research, Cell Cycle Proteins, Hematopoietic stem cell transplantation, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Gastroenterology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Central Nervous System Diseases, Recurrence, Antineoplastic Combined Chemotherapy Protocols, Prospective Studies, Young adult, Receptor, Notch1, Prospective cohort study, Hematopoietic Stem Cell Transplantation, Induction Chemotherapy, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, 3. Good health, Survival Rate, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Female, medicine.drug, Adult, medicine.medical_specialty, Cyclophosphamide, Adolescent, Ubiquitin-Protein Ligases, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, Maintenance Chemotherapy, 03 medical and health sciences, Young Adult, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, medicine, Humans, Survival rate, [ SDV ] Life Sciences [q-bio], L-Lactate Dehydrogenase, business.industry, F-Box Proteins, Lymphoblastic lymphoma, PTEN Phosphohydrolase, Induction chemotherapy, medicine.disease, Surgery, Consolidation Chemotherapy, ras Proteins, business, 030215 immunology
Abstract: Purpose This study evaluated the efficacy of pediatric-like acute lymphoblastic leukemia (ALL) therapy in adults with lymphoblastic lymphoma (LL). Patients and Methods This was a prospective phase II study in adults 18 to 59 years old with previously untreated LL. Patients were treated with an adapted pediatric-like ALL protocol, which included a corticosteroid prephase, a five-drug induction reinforced by sequential cyclophosphamide administration, dose-dense consolidation, late intensification, CNS prophylaxis, and a 2-year maintenance phase. Treatment response was assessed by computed tomography and optional positron emission tomography. Allogeneic hematopoietic stem cell transplant was offered to selected patients in first complete remission (CR) or unconfirmed CR. Results The study enrolled 148 patients (131 with T-lineage LL [T-LL] and 17 with B-lineage LL [B-LL]). A total of 119 patients with T-LL (90.8%) and 13 with B-LL (76.5%) reached CR/unconfirmed CR, including 26 with T-LL and two with B-LL who needed a second induction salvage course. Relapse occurred in 34 patients with T-LL and four with B-LL. In patients with T-LL, 3-year event-free survival was 63.3% (95% CI, 54.2% to 71.0%), disease-free survival was 72.4% (95% CI, 63.0% to 79.7%), and overall survival was 69.2% (95% CI, 60.0% to 76.7%). Multivariate analysis identified serum lactate dehydrogenase level and the NOTCH1/FBXW7/RAS/PTEN oncogene (a four-gene oncogenetic classifier) status but not positron emission tomography or hematopoietic stem cell transplant as independent prognostic factors for outcome in T-LL. Conclusion In adults with LL, an intensive pediatric-like ALL treatment protocol was associated with a good response rate and outcome. In patients with T-LL, the four-gene oncogenetic classifier and lactate dehydrogenase level were independent prognostic indicators.
Published: 2016

24. Efficacy of two injection-site localisation techniques for botulinum toxin injections: a single-blind, crossover, randomised trial protocol among adults with hemiplegia due to stroke

Author: Nicolas Andant, Armand Bonnin, Emmanuel Coudeyre, Isabelle Hauret, Bruno Pereira, Claire Morel, Service de Médecine Physique et de Réadaptation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Hôpital Corentin Celton [Issy-les-Moulineaux], Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université d'Auvergne - Clermont-Ferrand I (UdA), Centre Hospitalier Etienne Clémentel, Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Hôpital Corentin Celton [Issy-les-Moulineaux], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université d'Auvergne (Clermont Ferrand 1) (UdA), Unité de Biostatistiques, Centre Hospitalier Universitaire de Clermont-Ferrand, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Hôpitaux Universitaires Paris Ouest - Hôpital Corentin Celton [Issy-les-Moulineaux], Université d'Auvergne (Clermont Ferrand 1) ( UdA ), Unité de Nutrition Humaine - Clermont Auvergne ( UNH ), Université Clermont Auvergne ( UCA ) -Institut national de la recherche agronomique [Auvergne/Rhône-Alpes] ( INRA Auvergne/Rhône-Alpes ), and Coudeyre, Emmanuel
Subjects: Male, 030506 rehabilitation, Neurology, Palpation, essai clinique, 0302 clinical medicine, Clinical Protocols, gastrocnemius, Clinical endpoint, Protocol, Medicine, Single-Blind Method, Prospective Studies, Botulinum Toxins, Type A, Range of Motion, Articular, Stroke, Ultrasonography, Aged, 80 and over, Cross-Over Studies, medicine.diagnostic_test, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, electrostimulation, clinical trial, General Medicine, Middle Aged, Botulinum toxin, 3. Good health, Santé publique et épidémiologie, Treatment Outcome, Neuromuscular Agents, Muscle Spasticity, Female, France, patient, medicine.symptom, 0305 other medical science, Range of motion, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Modified Ashworth scale, Médecine humaine et pathologie, Hemiplegia, accident vasculaire cérébral, Injections, Intramuscular, Rehabilitation Medicine, 03 medical and health sciences, Young Adult, Physical medicine and rehabilitation, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Humans, Spasticity, Aged, soleus, business.industry, echography, medicine.disease, Physical therapy, Human health and pathology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: This work was supported by CHU Clermont-Ferrand, and IPSEN provided funding for the ultrasound; INTRODUCTION: Botulinum toxin injections are an effective treatment for limb spasticity following stroke. Different tracking techniques are used for this purpose: palpation, electrostimulation, electromyography and ultrasound. Yet very few studies have compared these different techniques, and none has successfully proved the superior efficacy of ultrasound-guided injections compared to another tracking method. The primary objective of our study was therefore to compare the efficacy of botulinum toxin injections depending on the tracking technique used: ultrasound versus electrostimulation. METHODS AND ANALYSIS: This is a clinical, single-centre, prospective, interventional, single-blind, crossover, randomised trial. In total, 30 patients aged between 18 and 80 years presenting with triceps surae spasticity (evaluated >1 on the modified Ashworth scale) associated with hemiplegia sequelae due to stroke will be included. The patients will be selected among those who attend for consultation the Physical Medicine and Rehabilitation Department of the Clermont-Ferrand University Hospital. One group will receive the abobotulinumtoxinA (BoNT-A) injection guided by electrostimulation then ultrasound, and the second group's botulinum toxin injections will be guided by ultrasound then electrostimulation. For each patient, the duration of study participation is 5 months. The primary end point is variation in passive ankle dorsiflexion range of motion at slow and high speeds (Tardieu scale) with the knee straight. ETHICS AND DISSEMINATION: This study received ethics approval form the CPP of Rhones-Alpes region. Results will be published in a peer-reviewed journal
Published: 2016

25. The effects of foot reflexology on symptoms of discomfort in palliative care: a feasibility study

Author: Marie Lavarelo Marcolin, Andréa Tarot, Véronique Lombardo, Bruno Pereira, Axelle Van Lander, Virginie Guastella, Centre de Soins Palliatifs [CHU Clermont-Ferrand] (CSP), CHU Louise Michel [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, AutomédiCation aCcompagnement Pluriprofessionnel PatienT (ACCePPT), Université Clermont Auvergne (UCA), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Neuro-Dol (Neuro-Dol), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)
Subjects: Massage therapy, Complementary and alternative medicine, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.PSYC]Cognitive science/Psychology, Foot reflexology Massage therapy Palliative care Sleep quality Anxiety Pain sleep disorders, Foot reflexology, Palliative care, [SDV.CAN]Life Sciences [q-bio]/Cancer, Sleep quality, Anxiety, Pain sleep disorders, [SDV.ETH]Life Sciences [q-bio]/Ethics
Abstract: Background In palliative care, the relief of discomfort is sought by an overall approach, combining prescribed medication and additional therapies, such as foot reflexology (FR). The main objective of this study was to assess the feasibility of FR in a population of inpatients in a palliative care unit (PCU).The precariousness of the patients led us to perform a feasibility study and not a cohort study from the outset. Its secondary objective was to assess the impact of an FR session on some symptoms of discomfort (anxiety, pain, troubled sleep, and psychological distress). Methods This is a feasibility study designed as a randomized controlled two-arm therapeutic trial. One arm tested FR, the other an active control, massage therapy (MT). The evaluators were blinded. Results FR was feasible for 14 patients out of the 15 included in the FR group (95% CI [68%; 100%]). These patients were in the palliative care phase of cancer, motor neuron disease, or terminal organ failure. Concerning the symptoms of discomfort, ESAS sleep quality score was on average 3.9 (± 2.5) before a session in the FR group. It was improved to an average of 3 (± 2.3) on the day after the session (effect-size = 0.38 [0.03; 0.73]). Conclusion This study confirms the feasibility of an FR session for patients hospitalized in a PCU. It resulted in a slight improvement in sleep quality. For other discomfort symptoms such as anxiety, pain and distress, FR yielded a non-significant improvement. Significant results would have needed a larger cohort.
Published: 2023

26. Fructose Malabsorption in Systemic Sclerosis

Author: Isabelle Marie, Philippe Ducrotté, Guillaume Gourcerol, Hervé Levesque, Jean-François Ménard, Anne-Marie Leroi, Service de Médecine Interne [Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Service de physiologie digestive, urinaire, respiratoire et de l'exercice [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Unité de biostatistiques [Rouen], CHU Rouen, Service d'Hépato-Gastroentérologie [Rouen], Service de Médecine Interne [CHU Rouen], Service de physiologie digestive, urinaire, respiratoire et de l'exercice [CHU Rouen], Normandie Université (NU)-Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de biostatistiques [CHU Rouen], Service d'Hépato-Gastroentérologie [CHU Rouen], and Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN)
Subjects: Adult, Male, medicine.medical_specialty, Malabsorption, Observational Study, Fructose malabsorption, Fructose, Gastroenterology, chemistry.chemical_compound, Malabsorption Syndromes, Risk Factors, Internal medicine, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Prospective Studies, skin and connective tissue diseases, ComputingMilieux_MISCELLANEOUS, Aged, 2. Zero hunger, Breath test, Intestinal permeability, Scleroderma, Systemic, Gastric emptying, medicine.diagnostic_test, integumentary system, business.industry, Fructose Intolerance, General Medicine, Middle Aged, medicine.disease, 3. Good health, Diet, Diarrhea, Endocrinology, chemistry, Breath Tests, Female, medicine.symptom, business, Research Article
Abstract: The deleterious effect of fructose, which is increasingly incorporated in many beverages, dairy products, and processed foods, has been described; fructose malabsorption has thus been reported in up to 2.4% of healthy subjects, leading to digestive clinical symptoms (eg, pain, distension, diarrhea). Because digestive involvement is frequent in patients with systemic sclerosis (SSc), we hypothesized that fructose malabsorption could be responsible for intestinal manifestations in these patients. The aims of this prospective study were to: determine the prevalence of fructose malabsorption, in SSc; predict which SSc patients are at risk of developing fructose malabsorption; and assess the outcome of digestive symptoms in SSc patients after initiation of standardized low-fructose diet. Eighty consecutive patients with SSc underwent fructose breath test. All SSc patients also completed a questionnaire on digestive symptoms, and a global symptom score (GSS) was calculated. The prevalence of fructose malabsorption was as high as 40% in SSc patients. We also observed a marked correlation between the presence of fructose malabsorption and: higher values of GSS score of digestive symptoms (P = 0.000004); and absence of delayed gastric emptying (P = 0.007). Furthermore, in SSc patients with fructose malabsorption, the median value of GSS score of digestive symptoms was lower after initiation of standardized low-fructose diet (4 before vs. 1 after; P = 0.0009). Our study underscores that fructose malabsorption often occurs in SSc patients. Our findings are thus relevant for clinical practice, highlighting that fructose breath test is a helpful, noninvasive method by: demonstrating fructose intolerance in patients with SSc; and identifying the group of SSc patients with fructose intolerance who may benefit from low-fructose diet. Interestingly, because the present series also shows that low-fructose diet resulted in a marked decrease of gastrointestinal clinical manifestations in SSc patients with fructose malabsorption, our findings underscore that fructose malabsorption may play a significant role in the onset of gastrointestinal symptoms in these patients. Finally, we suggest that fructose malabsorption may be due to reduced fructose absorption by enterocytes, impaired enteric microbiome, and decreased intestinal permeability.
Published: 2015

27. Correlation between Density of CD8+ T-cell Infiltrate in Microsatellite Unstable Colorectal Cancers and Frameshift Mutations: A Rationale for Personalized Immunotherapy

Author: Pauline Maby, Bernhard Mlecnik, Jérôme Leprince, Jérôme Galon, Gabriela Bindea, Pierre Michel, Richard Sesboüé, Jacques Benichou, Thierry Frebourg, Emilie Fauquembergue, David Tougeron, Aurélie Drouet, Nicolas Elie, Jean-Baptiste Latouche, Jean-Christophe Sabourin, Hafid Kora, Jean-Jacques Tuech, Tessa Fredriksen, Florence Le Pessot, Mohamad Hamieh, Jacques Mauillon, Helen K. Angell, Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut des Nanosciences de Paris (INSP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique (LHEEA), École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Neuroendocrinologie cellulaire et moléculaire, Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), CHU Rouen, Normandie Université (NU), Service de chirurgie digestive [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Hôpital Charles Nicolle [Rouen], Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Service de chirurgie digestive [Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Caen Normandie (UNICAEN), Différenciation et communication neuronale et neuroendocrine (DC2N), Unité de biostatistiques [Rouen], Service de génétique [Rouen], Service d'Anatomie et Cytologie Pathologique [Rouen], Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, Laboratoire d'éthique médicale et médecine légale (LEM), Service d'Hépato-Gastroentérologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de biostatistiques [CHU Rouen], Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Service d'Hépato-Gastroentérologie [CHU Rouen], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Université de Bordeaux (UB)
Subjects: Male, Cancer Research, Colorectal cancer, MESH: Immunotherapy, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV]Life Sciences [q-bio], [CHIM.THER]Chemical Sciences/Medicinal Chemistry, CD8-Positive T-Lymphocytes, 0302 clinical medicine, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Cytotoxic T cell, Precision Medicine, MESH: Lymphocytes, Tumor-Infiltrating, Frameshift Mutation, 0303 health sciences, MESH: Antigen-Presenting Cells, MESH: Frameshift Mutation, FOXP3, Forkhead Transcription Factors, MESH: Colorectal Neoplasms, Hereditary Nonpolyposis, MESH: CD8-Positive T-Lymphocytes, Lynch syndrome, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Female, Microsatellite Instability, Immunotherapy, Colorectal Neoplasms, congenital, hereditary, and neonatal diseases and abnormalities, Antigen-Presenting Cells, Biology, MESH: Precision Medicine, Frameshift mutation, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, MESH: Forkhead Transcription Factors, medicine, Humans, 030304 developmental biology, MESH: Humans, Microsatellite instability, medicine.disease, Colorectal Neoplasms, Hereditary Nonpolyposis, MESH: Male, Immunology, Cancer research, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, TCF7L2, MESH: Female, MESH: Colorectal Neoplasms, MESH: Microsatellite Instability
Abstract: Colorectal cancers with microsatellite instability (MSI) represent 15% of all colorectal cancers, including Lynch syndrome as the most frequent hereditary form of this disease. Notably, MSI colorectal cancers have a higher density of tumor-infiltrating lymphocytes (TIL) than other colorectal cancers. This feature is thought to reflect the accumulation of frameshift mutations in sequences that are repeated within gene coding regions, thereby leading to the synthesis of neoantigens recognized by CD8+ T cells. However, there has yet to be a clear link established between CD8+ TIL density and frameshift mutations in colorectal cancer. In this study, we examined this link in 103 MSI colorectal cancers from two independent cohorts where frameshift mutations in 19 genes were analyzed and CD3+, CD8+, and FOXP3+ TIL densities were quantitated. We found that CD8+ TIL density correlated positively with the total number of frameshift mutations. TIL densities increased when frameshift mutations were present within the ASTE1, HNF1A, or TCF7L2 genes, increasing even further when at least one of these frameshift mutations was present in all tumor cells. Through in vitro assays using engineered antigen-presenting cells, we were able to stimulate peripheral cytotoxic T cells obtained from colorectal cancer patients with peptides derived from frameshift mutations found in their tumors. Taken together, our results highlight the importance of a CD8+ T cell immune response against MSI colorectal cancer–specific neoantigens, establishing a preclinical rationale to target them as a personalized cellular immunotherapy strategy, an especially appealing goal for patients with Lynch syndrome. Cancer Res; 75(17); 3446–55. ©2015 AACR.
Published: 2015

28. Blastocystis Is Associated with Decrease of Fecal Microbiota Protective Bacteria: Comparative Analysis between Patients with Irritable Bowel Syndrome and Control Subjects

Author: Nourrisson, Céline, Scanzi, Julien, Pereira, Bruno, NkoudMongo, Christina, Wawrzyniak, Ivan, Cian, Amandine, Viscogliosi, Eric, Livrelli, Valérie, Delbac, Frédéric, Dapoigny, Michel, Poirier, Philippe, CHU Gabriel Montpied (CHU), CHU Clermont-Ferrand, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Neuro-Dol - Clermont Auvergne (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Unité de Biostatistiques, Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), 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 National de la Recherche Scientifique (CNRS), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Recherche Agronomique (INRA), Département d'Hépato-Gastroentérologie, Hôtel-Dieu-CHU Clermont-Ferrand-Université de Clermont-Ferrand, CHU Gabriel Montpied [Clermont-Ferrand], Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA), Moné, Anne, and 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 National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Dientamoeba Fragilis, [SDV]Life Sciences [q-bio], lcsh:Medicine, trouble intestinal, Blastocystis Infections, Pathology and Laboratory Medicine, Irritable Bowel Syndrome, Feces, flore intestinale, Signs and Symptoms, Medicine and Health Sciences, Parasitic Diseases, Humans, inflammation chronique, lcsh:Science, Aged, Protozoans, Microbiota, lcsh:R, Microbiology and Parasitology, microbiote fécal, Organisms, Biology and Life Sciences, parasite gastro intestinal, Middle Aged, Microbiologie et Parasitologie, Parasitic Protozoans, [SDV] Life Sciences [q-bio], Blastocystis Hominis Infection, Blastocystis, lcsh:Q, Female, Parasitology, Research Article
Abstract: International audience; Blastocystis is a protistan parasite living in the digestive tract of many animals, including humans. This highly prevalent intestinal parasite is suspected to be linked to Irritable Bowel Syndrome (IBS), a chronic functional bowel disorder. Here, we first compared the prevalence of Blastocystis among 56 IBS patients (40 IBS with constipation (IBS-C), 9 IBS with diarrhea (IBS-D), 4 mixed IBS (IBS-M) and 3 unsubtyped IBS (IBS-U) according to the Rome III criteria) and 56 control (i.e. without any diagnosed chronic or acute gastrointestinal disorder) subjects. The highest prevalence of Blastocystis spp. was observed in the IBS group, but was only statistically significant in men (36.8% in the IBS group versus 4.8% in the control group). We then conducted a meta-analysis including epidemiological studies attempting to determine whether Blastocystis carriage could be linked to IBS, and highlighted that IBS patients had a relative risk of 2.34 to be infected by Blastocystis when compared to non-IBS subjects. We also looked for Dientamoeba fragilis, which is often associated with IBS, and identified this parasite only in some IBS patients (n = 6/56). Several studies provided evidence for a major role of the gut microbiota in the pathophysiology of IBS. Thus, we investigated the possible impact of Blastocystis carriage on the enteric bacterial community through quantification of 8 major bacterial groups from the enteric flora. Our data indicated that men with IBS-C had a significant decrease in Bifidobacterium sp. when infected by Blastocystis. Interestingly, in control subjects (i.e. without any gastrointestinal disorder) positive for Blastocystis, Faecalibacterium prausnitzii, which is known for its anti-inflammatory properties, was significantly decreased in men. Our results support the hypothesis that Blastocystis might be linked to the pathophysiology of IBS-C and intestinal flora imbalance.
Published: 2014

29. L1 chimeric transcripts are expressed in healthy brain and their deregulation in glioma follows that of their host locus

Author: Marie-Elisa Pinson, Franck Court, Aymeric Masson, Yoan Renaud, Allison Fantini, Ophélie Bacoeur-Ouzillou, Marie Barriere, Bruno Pereira, Pierre-Olivier Guichet, Emmanuel Chautard, Lucie Karayan-Tapon, Pierre Verrelle, Philippe Arnaud, Catherine Vaurs-Barrière, BARRIERE, Catherine, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Cancérologie Biologique [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Institut Curie [Paris], Laboratoire de neurosciences expérimentales et cliniques (LNEC), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
Subjects: Retroelements, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Brain, [SDV.CAN]Life Sciences [q-bio]/Cancer, Glioma, General Medicine, Long Interspersed Nucleotide Elements, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, Humans, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Promoter Regions, Genetic, Molecular Biology, Genetics (clinical)
Abstract: Besides the consequences of retrotransposition, long interspersed element 1 (L1) retrotransposons can affect the host genome through their antisense promoter. In addition to the sense promoter, the evolutionarily recent L1 retrotransposons, which are present in several thousand copies, also possess an anti-sense promoter that can produce L1 chimeric transcripts (LCT) composed of the L1 5′ UTR followed by the adjacent genomic sequence. The full extent to which LCT expression occurs in a given tissue and whether disruption of the defense mechanisms that normally control L1 retrotransposons affects their expression and function in cancer cells, remain to be established. By using CLIFinder, a dedicated bioinformatics tool, we found that LCT expression was widespread in normal brain and aggressive glioma samples, and that approximately 17% of recent L1 retrotransposons, from the L1PA1 to L1PA7 subfamilies, were involved in their production. Importantly, the transcriptional activities of the L1 antisense promoters and of their host loci were coupled. Accordingly, we detected LCT-producing L1 retrotransposons mainly in transcriptionally active genes and genomic loci. Moreover, changes in the host genomic locus expression level in glioma were associated with a similar change in LCT expression level, regardless of the L1 promoter methylation status. Our findings support a model in which the host genomic locus transcriptional activity is the main driving force of LCT expression. We hypothesize that this model is more applicable when host gene and LCT are transcribed from the same strand.
Published: 2022

30. Late toxicity comparison of alkylating-based maintenance regimen with cyclophosphamide (VAC) vs ifosfamide (VAI) in Ewing sarcoma survivors treated in the randomized clinical trial Euro-EWING99-R1 in France

Author: Victoria, Corvest, Perrine, Marec-Bérard, Cyril, Lervat, Hélène, Pacquement, Maud, Toulmonde, Jean-Claude, Gentet, Valérie, Laurence, Morgane, Cleirec, Ludovic, Mansuy, Emmanuelle, Bompas, Marie-Pierre, Castex, Sophie, Taque, Bruno, Filhon, Marie-Dominique, Tabone, Cécile, Verité, Natacha, Entz-Werle, Laure, Saumet, Gregory, Guimard, Morgane, Pondrom, Christine, Chevreau, Jennifer, Flandrin, Lise, Duranteau, Christine, Rousset-Jablonski, Laurence, Brugières, Marta, Jimenez, Marie-Cécile, Le Deley, Nathalie, Gaspar, Brice, Fresneau, Institut Gustave Roussy (IGR), Centre Léon Bérard [Lyon], Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Institut Curie [Paris], Institut Bergonié [Bordeaux], UNICANCER, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CRLCC René Gauducheau, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Pontchaillou [Rennes], CHU Rouen, Normandie Université (NU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, CHU Strasbourg, Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire de Nice (CHU Nice), Institut Claudius Regaud, Unité de Biostatistiques [Toulouse] ( Institut Claudius Regaud / IUCT-O), Institut Claudius Regaud-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)-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), Hôpital Bicêtre, Research on Healthcare Performance (RESHAPE - Inserm U1290 - UCBL1), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave-Roussy, Centre Léon Bérard, CLB, Thanks to the investigators of the following French centers which contributed patients to our study: Centre Léon Bérard, medical oncology, Lyon, CHU St Etienne, CHU Clermont Ferrand, CHU Amiens, Regional Cancer Center, Nancy, Regional Cancer Center, Caen, CHU Besançon, Institut Gustave-Roussy, medical oncology, Villejuif, CHU Tours, CHU Marseille, CHU Grenoble, Regional Cancer Center, Dijon, Regional Cancer Center, Clermont Ferrand, Lenval Hospital, Nice, Regional Cancer Center, Angers, and CHU Rouen.
Subjects: cyclophosphamide/adverse effects, child, Ewing/drug therapy, antineoplastic combined chemotherapy protocols/adverse effects, [SDV.CAN]Life Sciences [q-bio]/Cancer, Ifosfamide/adverse effects
Abstract: International audience; In Euro-EWING99-R1 randomized trial, cyclophosphamide was shown to be noninferior to ifosfamide in the consolidation of standard-risk Ewing sarcoma (SR-EWS) after a common induction with VIDE (vincristine-ifosfamide-doxorubicin-etoposide). We present the results of the late effects analysis of VAC (vincristine-dactinomycin-cyclophoshamide) vs VAI (vincristine-dactinomycin-ifosfamide) conducted in Euro-EWING99-R1 French cohort. Of 267 French randomized patients, 204 were alive and free-of-relapse at 5-years including 172 with available long-term follow-up data concerning cardiac, renal and/or gonadal functions (sex-ratio M/F = 1.3, median age at diagnosis = 14 years): 84 randomized in VAC (median cumulative doses: cyclophosphamide = 9.7 g/m2, ifosfamide = 59.4 g/m2) and 88 in VAI (ifosfamide = 97.1 g/m2). With a median follow-up of 10 years (range = 5-17), five late relapses and five second malignancies were recorded. The 10-year event-free survival among 5-year free-of-relapse survivors was similar between VAC and VAI (93% vs 95%, P =.63). We estimated the 10-year cumulative probabilities of cardiac and kidney toxicities at 4.4% (95% confidence interval [95% CI] = 1.1%-7.6%) and 34.8% (95% CI = 26.8%-42.0%), respectively. Cardiac toxicity cumulative probability was similar in both arms, whereas kidney toxicity was higher in VAI (at 10 years, 43.0% vs 25.7%, P =.02), resulting from significant difference in glomerular toxicity (31.1% vs 13.1%, P
Published: 2023

31. Effect of subtherapeutic and therapeutic sulfamethazine concentrations on transcribed genes and translated proteins involved in Microbacterium sp. C448 resistance and degradation

Author: Paris, Laurianne, Devers-Lamrani, Marion, Joly, Muriel, Viala, Didier, de Antonio, Marie, Pereira, Bruno, Rouard, Nadine, Besse-Hoggan, Pascale, Hébraud, Michel, Topp, Edward, Martin-Laurent, Fabrice, Batisson, Isabelle, Laboratoire Microorganismes : Génome et Environnement (LMGE), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Institut de Chimie de Clermont-Ferrand (ICCF), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Agroécologie [Dijon], Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Dijon, 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), Plateforme Exploration du Métabolisme (PFEM), MetaboHUB-Clermont, MetaboHUB-MetaboHUB-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Biostatistics unit (DRCI), CHU Clermont-Ferrand, Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Microbiologie Environnement Digestif Santé (MEDIS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), London Research and Development Centre (LRDC), and University of Western Ontario (UWO)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience; Abstract Microbacterium sp. C448, isolated from a soil regularly exposed to sulfamethazine (SMZ), can use various sulphonamide antibiotics as the sole carbon source for growth. The basis for the regulation of genes encoding the sulphonamide metabolism pathway, the dihydropteroate synthase sulphonamide target (folP), and the sulphonamide resistance (sul1) genes, is unknown in this organism. In the present study, the response of the transcriptome and proteome of Microbacterium sp. C448 following exposure to subtherapeutic (33 µM) or therapeutic (832 µM) SMZ concentrations was evaluated. Therapeutic concentration induced the highest sad expression and Sad production, consistent with the activity of SMZ degradation observed in cellulo. Following complete SMZ degradation, Sad production tended to return to the basal level observed prior to SMZ exposure. Transcriptomic and proteomic kinetics were concomitant for the resistance genes and proteins. The abundance of Sul1 protein, 100-fold more abundant than FolP protein, did not change in response to SMZ exposure. Moreover, non-targeted analyses highlighted the increase of a deaminase RidA and a putative sulphate exporter expression and production. These two novel factors involved in the 4-aminophenol metabolite degradation and the export of sulphate residues formed during SMZ degradation, respectively, provided new insights into Microbacterium sp. C448 SMZ detoxification process.
Published: 2023

32. Un entraînement excentrique excessif chez des souris carencées en vitamine D conduit à une perte de capacités physiques, une atrophie musculaire et une inflammation systémique

Author: C. Norgieux, E. Burban, C. Giraudet, V. Patrac, J. Salles, O. Le Bacquer, L. Ouchchane, S. Walrand, R. Richard, J. Talvas, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), and CHU Clermont-Ferrand-CHU Clermont-Ferrand
Subjects: Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Internal Medicine
Abstract: International audience
Published: 2022

33. Identification of Responders to Balneotherapy among Adults over 60 Years of Age with Chronic Low Back Pain: A Pilot Study with Trajectory Model Analysis

Author: Benjamin Raud, Charlotte Lanhers, Cindy Crouzet, Bénédicte Eschalier, François Bougeard, Anna Goldstein, Bruno Pereira, Emmanuel Coudeyre, Service de Médecine Physique et de Réadaptation [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Louise Michel [Clermont-Ferrand], CHU Clermont-Ferrand, Université Clermont Auvergne (UCA), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA)
Subjects: Adult, Male, Balneology, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, balneotherapy, Pilot Projects, Middle Aged, Cohort Studies, aged, hydrotherapy, disability, [SDE]Environmental Sciences, chronic low back pain, Humans, Female, Prospective Studies, Low Back Pain
Abstract: Balneotherapy may be a relevant treatment for chronic low back pain (LBP) in individuals > 60 years old. This pilot study aimed to determine the effectiveness of balneotherapy for chronic LBP in people > 60 years old and to determine profiles of responders with trajectory model analysis. This was a pilot prospective open cohort study, with repeated measurements using validated questionnaires; participants were their own controls. The primary endpoint was the proportion of participants with a change in pain intensity between the start of treatment and 3 months after treatment assessed with a numeric scale (NS) from 0 to 100 mm, with an effect size (ES) > 0.5. The assessments involved questionnaires that were self-administered on days (D) 1 and 21 and at months 3 and 6. The secondary objective was to determine the profile of responders to balneotherapy. We included 78 patients (69.2% women), mean age 68.3 ± 5.3 years. The mean pain score on the NS was 48.8 ± 19.9 at D1 and 39.1 ± 20.5 at 3 months (p < 0.001). The ES was 0.47 [95% confidence interval [CI] 0.25 to 0.69] for the whole sample; 36% (28/78) had an ES > 0.5; 23% (18/78) had a moderate ES (0 to 0.5); and 41% (32/78) had an ES of zero (14/78) or < 0 (18/78), corresponding to increased pain intensity. The pain trajectory model showed that the change in pain between D1 and D21 for trajectory A (larger reduction in pain intensity) was −50% [95% CI −60 to −27], and for trajectory B (smaller reduction in pain intensity), it was −13% [−33 to 0] (p < 0.001). Between Day 1 and month 3, the change for trajectory A was −33% [−54; 0] and for trajectory B was −13% [−40 to 0] (p = 0.14). Finally, between D1 and month 6, the change for trajectory A was −50% [−60 to 0] and for trajectory B was −6% [−33 to 17] (p = 0.007). The patients in trajectory A reported performing more physical activity than those in trajectory B (p = 0.04). They were also less disabled, with a mean Oswestry Disability Index of 40.4 versus 45.7 for those in trajectory A and B, respectively, (p = 0.03) and had a higher total Arthritis Self-Efficacy Scale score. This real-life study of the effectiveness of balneotherapy on chronic LBP identified distinct pain trajectories and predictive variables for responders. These criteria could be used in decision-making regarding the prescription of balneotherapy, to ensure personalized management of chronic LBP.
Published: 2022

34. Cerebral atrophy is linked to clinical severity and worsens with aging in patients with Pelizaeus-Merzbacher disease and Spastic Paraplegia type 2

Author: Sarret, Catherine, Lemaire, Jean-Jacques, Sontheimer, Anna, Coste, Jerome, Pereira, Bruno, Feschet, Fabien, Roche, Basile, Renou, Jean-Pierre, Boespflug-Tanguy, Odile, Image Guided Clinical Neurosciences and Connectomics (IGCNC), Université d'Auvergne (Clermont Ferrand 1) (UdA), Institut de Recherche en Horticulture et Semences (IRHS), Université d'Angers (UA)-Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Hôpital Robert Debré, Département de Pédiatrie [Clermont-Ferrand], Université de Clermont-Ferrand, Institut Pascal - Clermont Auvergne (IP), Sigma CLERMONT (Sigma CLERMONT)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Université d'Auvergne - Clermont-Ferrand I (UdA), Service de Neurochirurgie [Clermont-Ferrand], CHU Clermont-Ferrand-Hôpital Gabriel Montpied, CHU Clermont-Ferrand, Unité de Biostatistiques, Délégation Recherche Clinique & Innovation, Centre de recherche de Clermont-Ferrand-Theix, Centre de recherche de Clermont-Ferrand-Theix, Institut National de la Recherche Agronomique (INRA), European Society of Neurological Pediatry, Service de Pédiatrie Générale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), AGROCAMPUS OUEST, 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)-Institut National de la Recherche Agronomique (INRA)-Université d'Angers (UA), International Society for Developmental Neuroscience (ISDN). INT., SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service de Neurochirurgie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], Qualité des Produits Animaux (QuaPA), and AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA)-Université d'Angers (UA)
Subjects: [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, atrophie, Pelizaeus-Merzbacher, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, musculoskeletal, neural, and ocular physiology, [SDV]Life Sciences [q-bio], vieillissement, nervous system diseases, gravity, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, nervous system, atrophy, ageing, gravité
Abstract: Événement(s) lié(s) : - 5. Annual NeuroDevNet Brain Development Conference; Montréal (CAN) - (2014-07-19 - 2014-07-24); International audience; Objective:This study aims to determine the natural history of genetic hypomyelinating disorders Pelizaeus–Merzbacher disease (PMD) and Spastic Paraplegia type 2 (SPG2) on magnetic resonance imaging (MRI) and to correlate MRI results with clinical severity.Methods:A prospective study in 35 patients with variable forms of PMD or SPG2 was performed on a total of 66 cerebral MRI. A myelination score and a global atrophy score were determined for each MRI. We also performed image segmentation to calculate corpus callosum area, cerebellum, white matter and gray matter volumes.Results:Multivariate analysis with adjustment to the age revealed a significant difference for global atrophy score and corpus callosum area in different subgroups of severity at the first MRI acquisition. Evolution of MRI over time showed an increasing score of myelination until the age of 12 years, followed by stabilization. On the contrary, global atrophy, atrophy of corpus callosum and cerebellum worsened in the majority of patients with aging. No change in gray matter and white matter proportions was noticed over time.Discussion:This study points out a correlation between cerebral atrophy and clinical severity in patients with PMD and SPG2 whereas degree of myelination was not clearly discriminating. It also highlighted, for the first time in a large cohort of patients, a clear inter- and intra-individual cerebral atrophy over time involving white and gray matter.
Published: 2014

35. Impact of COVID-19 Lockdown on Food Consumption and Behavior in France (COVISTRESS Study)

Author: Pouget, Mélanie, Clinchamps, Maëlys, Lambert, Céline, Pereira, Bruno, Farigon, Nicolas, Gentes, Elodie, Miolanne, Magalie, Picard, Mathilde, Tyrode, Anne, Alligier, Maud, Network, Covistress, Dutheil, Frédéric, Boirie, Yves, Service de Nutrition Clinique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Auvergne de l'Obésité et de ses Risques en Santé (CALORIS), Service Santé Travail Environnement [CHU Clermont-Ferrand], Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), FCRIN/FORCE Network, Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), WittyFit, Unité de Nutrition Humaine (UNH), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA)
Subjects: Nutrition and Dietetics, SARS-CoV-2, COVID-19, lockdown, eating habits, Feeding Behavior, Communicable Disease Control, [SCCO.PSYC]Cognitive science/Psychology, Humans, Life Style, Pandemics, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Food Science
Abstract: International audience; The COVID-19 pandemic and subsequent lockdowns modified work environments, lifestyles, and food consumption. Eating habits and mood changes in a French population during the first lockdown were examined using an online self-reported questionnaire with REDCap software through the COVISTRESS.ORG website. In 671 French participants, the main changes during lockdown were increased stress levels (64 [23; 86] vs. 3 [0; 18]) and sedentary behavior (7 [4; 9] vs. 5 [3; 8] hours per day), a deterioration in sleep quality (50 [27; 83] vs. 70 [48; 94]) and mood (50 [30; 76] vs. 78 [50; 92]), and less physical activity (2.0 [0.5; 5.0] vs. 3.5 [2.0; 6.0]). Mood was modified, with more anger (56 [39; 76] vs. 31 [16; 50]), more sadness (50 [34; 72] vs. 28 [16; 50]), more agitation (50 [25; 66] vs. 43 [20; 50]), and more boredom (32 [7; 60] vs. 14 [3; 29]). A total of 25% of the participants increased their consumption of alcoholic beverages, 29% their consumption of sugary foods, and 26% their consumption of cocktail snacks. A multiple-correspondence analysis highlights four different profiles according to changes in eating habits, food consumption, lifestyle, and mood. In conclusion, eating habits and lifestyle changes during lockdown periods should be carefully monitored to promote healthy behaviors.
Published: 2022
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36. Objective evaluation of the first post-lockdown on physical activity, sedentary behavior and food choice in a sample of French young adult students

Author: Sylvie Rousset, Maxime Douarre, Alix Poyet, Fadi Bounechada, Anne Descouls, Camille Girardin, Bruno Pereira, Frédéric Dutheil, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut de Médecine du Travail, CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Service Santé Travail Environnement [CHU Clermont-Ferrand], and CHU Gabriel Montpied [Clermont-Ferrand]
Subjects: Comportement sédentaire, Epidemiology, Physical activity, [SDV]Life Sciences [q-bio], Public Health, Environmental and Occupational Health, Food choice, COVID-19, ÉtudiantCOVID-19 [feminine], Choix de nourriture, Activité physique, Sedentary behavior, Lockdown, [SCCO.PSYC]Cognitive science/Psychology, Student, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Confinement
Abstract: International audience; De mi-mars à début mai 2020, la France a limité les activités de plein air à une heure par jour en raison de l'épidémie de Covid-19. Ce confinement intérieur pourrait avoir un impact durable sur les activités sédentaires et physiques post-confinement et les choix alimentaires. L'objectif de cette étude est de comparer les comportements avant et après le confinement chez un échantillon de jeunes étudiants adultes français (sex ratio = 1:1, 22 ± 3 ans). Sur une période de 4 jours en avril et après la mi-mai 2020, 50 étudiants ont utilisé l'application pour smartphone WellBeNet pour enregistrer l' accélérométriedes données pour évaluer leur comportement sédentaire et leur activité physique, et leur consommation alimentaire. Certains comportements sont restés stables pour les deux périodes : comportement sédentaire, activité peu intense, nombre de repas par jour, nombre de portions de fruits, noix, laitages, légumes, légumineuses et viande-poisson-œuf. La durée d'activité d'intensité modérée était plus élevée (+1,4 %, p < 0,0001), tandis que le score d'équilibre alimentaire était plus faible (−0,3, p = 0,06) lors du retour aux conditions de vie libre. Des comportements alimentaires différents chez les garçons et les filles ont été observés entre les deux périodes. Le nombre total quotidien de portions alimentaires et de féculents entiers post-confinement était plus faible chez les étudiantes (−1,07 et −0,47 portion/j, p = 0,07 et 0,04) mais restait stable chez les garçons, post-confinement. La consommation de collations était similaire chez les hommes et les femmes pendant le confinement, alors qu'elle était plus élevée chez les hommes après le confinement (+0,8 portion/j, p = 0,01). Pendant le confinement lié au COVID-19, le choix de consommation alimentaire était globalement meilleur et l'intensité modéréele niveau d'activité physique était inférieur à celui de la période subséquente de vie libre.
Published: 2022

37. CEA, CA19-9, circulating DNA and circulating tumour cell kinetics in patients treated for metastatic colorectal cancer (mCRC)

Author: David Sefrioui, Ludivine Beaussire, André Gillibert, France Blanchard, Emmanuel Toure, Céline Bazille, Anne Perdrix, Frédéric Ziegler, Alice Gangloff, Mélanie Hassine, Caroline Elie, Anne-Laure Bignon, Aurélie Parzy, Philippe Gomez, Caroline Thill, Florian Clatot, Jean-Christophe Sabourin, Thierry Frebourg, Jacques Benichou, Karine Bouhier-Leporrier, Marie-Pierre Gallais, Nasrin Sarafan-Vasseur, Pierre Michel, Frédéric Di Fiore, 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), Normandie Université (NU), Unité de biostatistiques [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Département de Pathologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Laboratoire de biochimie générale [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre hospitalier universitaire de Rouen, Hepatogastroenterologie, chu Elbeuf Les Feugrais, Hepatogastroenterology, Caen University Hospital, Caen., Department of Hepatogastroenterology, Caen University Hospital, Departement Hepatogastroenterologie, Centre Francois Baclesse, Caen, Medical Oncology, centre Frédéric Joliot, Département de génétique [CHU Rouen] (Centre Normandie de Génomique et de Médecine Personnalisée), Service d'Hépato-Gastroentérologie [CHU Rouen], and Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN)
Subjects: Adult, Male, Cell kinetics, Oncology, Cancer Research, medicine.medical_specialty, Scoring system, endocrine system diseases, Colorectal cancer, medicine.medical_treatment, Article, Circulating Tumor DNA, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, Humans, Antigens, Tumor-Associated, Carbohydrate, In patient, Prospective Studies, Neoplasm Metastasis, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Chemotherapy, business.industry, Middle Aged, Neoplastic Cells, Circulating, medicine.disease, Survival Analysis, digestive system diseases, Carcinoembryonic Antigen, Up-Regulation, 3. Good health, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Circulating DNA, Female, CA19-9, Colorectal Neoplasms, business, Progressive disease
Abstract: BACKGROUND: We previously reported that CEA kinetics are a marker of progressive disease (PD) in metastatic colorectal cancer (mCRC). This study was specifically designed to confirm CEA kinetics for predicting PD and to evaluate CA19-9, cell-free DNA (cfDNA), circulating tumour DNA (ctDNA) and circulating tumour cell (CTC) kinetics. METHODS: Patients starting a chemotherapy (CT) with pre-treatment CEA > 5 ng/mL and/or CA19.9 > 30 UI/mL were prospectively included. Samples were collected from baseline to cycle 4 for CEA and CA19-9 and at baseline and the sixth week for other markers. CEA kinetics were calculated from the first to the third or fourth CT cycle. RESULTS: A total of 192 mCRC patients were included. CEA kinetics based on the previously identified >0.05 threshold was significantly associated with PD (p
Published: 2021

38. Ustekinumab is more effective than azathioprine to prevent endoscopic postoperative recurrence in Crohn's disease

Author: Buisson, Anthony, Nancey, Stéphane, Manlay, Luc, Rubin, David, Hebuterne, Xavier, Pariente, Benjamin, Fumery, Mathurin, Laharie, David, Roblin, Xavier, Bommelaer, Gilles, Pereira, Bruno, Peyrin‐biroulet, Laurent, Vuitton, Lucine, Post-Op Study Grp, Ustek, Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service d'Hépatogastroentérologie [CHU Lyon-Sud], Hospices Civils de Lyon (HCL), The University of Chicago Medicine [Chicago], Servcie Hépato-gastroentérolgie et Nutrition clinique [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), Service Gastro-entérologie adulte – Maladies de l’appareil digestif [CHU Lille], CHU Lille, Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Service Gastroentérologie [CHU Bordeaux], Centre Hospitalier Universitaire de Bordeaux (CHU Bordeaux), Service de Gastro-entérologie et Hépatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Gastro-Entérologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), 'Francois Aupetit' Association (AFA CrohnRCH), CHU Clermont-Ferrand (DRCI), Centre Hospitalier Universitaire de Lille (CHU Lille), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de l'Environnement Industriel et des Risques, Service de gastroentérologie [CHU Saint-Etienne], and Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Azathioprine, Antibodies, Monoclonal, Humanized, Gastroenterology, ustekinumab, law.invention, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Gastrointestinal Agents, Randomized controlled trial, Recurrence, law, Internal medicine, Ustekinumab, Secondary Prevention, medicine, Clinical endpoint, Humans, postoperative recurrence, Propensity Score, Retrospective Studies, Crohn's disease, azathioprine, business.industry, Inflammatory Bowel Disease, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Bowel resection, medicine.disease, Control Groups, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Cohort, Propensity score matching, Original Article, Female, 030211 gastroenterology & hepatology, business, Immunosuppressive Agents, medicine.drug
Abstract: International audience; Background: Preventing postoperative recurrence (POR) is a major concern in Crohn's disease (CD). While azathioprine is an option, no data is available on ustekinumab efficacy in this situation.Aims: We compared the effectiveness of ustekinumab versus azathioprine in preventing endoscopic POR in CD.Methods: We retrospectively collected data from all consecutive CD patients treated with ustekinumab after intestinal resection in 9 centers. The control group (azathioprine alone) was composed of patients who participated in a randomized controlled trial conducted in the same centers comparing azathioprine alone or in combination with curcumin. Propensity score analyses (inversed probability of treatment weighting = IPTW) were applied to compare the two groups. The primary endpoint was endoscopic POR (Rutgeerts' index ≥ i2) at 6 months.Results: Overall, 32 patients were included in the ustekinumab group and 31 in the azathioprine group. The propensity score analysis was adjusted on the main risk factors (smoking, fistulizing phenotype, prior bowel resection, resection length >30 cm and ≥2 biologics before surgery) and thiopurines or ustekinumab exposure prior to surgery making the two arms comparable (∣d∣ < 0.2). After IPTW, the rate of endoscopic POR at 6 months was lower in patients treated with ustekinumab compared to azathioprine (28.0% vs. 54.5%, p = 0.029). After IPTW, the rates of i2b-endoscopic POR (Rutgeerts' index ≥ i2b) and severe endoscopic POR (Rutgeerts' index ≥ i3) were 20.8% versus 42.5% (p = 0.066) and 16.9% versus 27.9% (p = 0.24), in the ustekinumab and azathioprine groups, respectively.Conclusion: Ustekinumab seemed to be more effective than azathioprine in preventing POR in this cohort of CD patients.
Published: 2021

39. Prognostic factors of paraneoplastic pemphigus

Author: Luc Thomas, Saskia Ingen-Housz-Oro, Sandy Léger, Gilles Chaumentin, Caroline Robert, Pierre-Jean Weiller, Philippe Courville, Fabienne Léonard, Pascal Joly, Laurent Machet, Stéphane Debarbieux, Estelle Houivet, M. Dandurand, Francis Carsuzaa, Jacqueline Chevrant-Breton, Jean-Philippe Arnault, François Aubin, Denis Jullien, Michel D'Incan, Gérard Guillet, Olivier Chosidow, Catherine Lok, Jean-Philippe Lacour, Vincent Ferranti, Danièle Gilbert, Damien Picard, Marie-Sylvie Doutre, I. Kupfer, Olivier Dereure, Jacques Benichou, Carle Paul, Béatrice Crickx, Emmanuel Delaporte, Jean-Michel Pignon, Ludovic Martin, Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Littoral, Environnement, Télédétection, Géomatique (LETG-Angers), Littoral, Environnement, Télédétection, Géomatique UMR 6554 (LETG), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université d'Angers (UA)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Brest (UBO)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Géographie et d'Aménagement Régional de l'Université de Nantes (IGARUN), Université de Nantes (UN)-Université de Nantes (UN)-Université de Caen Normandie (UNICAEN), Université de Nantes (UN)-Université de Nantes (UN), 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), Service de Dermatologie, Hôtel-Dieu, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Department of Dermatology, Université d'Angers (UA), Service de dermatologie, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de Dermatologie, Centre Hospitalier Sud, Hospices Civils, Lyon, Protéines de défense des réponses immune et inflammatoire : identification, régulation et rôles physiopathologiques, Unité de biostatistiques [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire d'Etudes Environnementales des Systèmes Anthropisés, Université d'Angers ( UA ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Hospices Civils de Lyon ( HCL ), Institut Gustave Roussy ( IGR ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Unité de biostatistiques [Rouen], and CHU Rouen-Université de Rouen Normandie ( UNIROUEN )
Subjects: Male, Erythema, Paraneoplastic Syndromes, Kaplan-Meier Estimate, Severity of Illness Index, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 030207 dermatology & venereal diseases, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, Adrenal Cortex Hormones, Neoplasms, Erythema multiforme, Aged, 80 and over, Univariate analysis, integumentary system, Mortality rate, Castleman disease, Hazard ratio, General Medicine, Middle Aged, Prognosis, 3. Good health, 030220 oncology & carcinogenesis, Female, medicine.symptom, Rituximab, Immunosuppressive Agents, Adult, medicine.medical_specialty, Dystonin, [SDV.CAN]Life Sciences [q-bio]/Cancer, Nerve Tissue Proteins, Dermatology, 03 medical and health sciences, medicine, Humans, Immunologic Factors, Protein Precursors, Aged, Autoantibodies, Proportional Hazards Models, Retrospective Studies, Erythema Multiforme, Mucous Membrane, Proportional hazards model, business.industry, Plakins, Membrane Proteins, medicine.disease, Cytoskeletal Proteins, Paraneoplastic pemphigus, Desmoplakins, Multivariate Analysis, business, Carrier Proteins, Pemphigus
Abstract: International audience; OBJECTIVE To identify the prognostic factors of overall survival in a series of patients with paraneoplastic pemphigus (PNP). DESIGN Multicenter retrospective cohort study. SETTING Twenty-seven dermatology departments in France. PATIENTS A total of 53 patients (31 men and 22 women; median age, 59 years; age range, 30-88 years) were diagnosed as having PNP between 1992 and 2010. MAIN OUTCOME MEASURES Overall Kaplan-Meier survival rates were estimated, and features associated with survival were assessed using univariate (log-rank test) and multivariate (Cox regression) analyses. RESULTS The study included 53 patients with PNP. Thirty-six patients (68%) died during the study. The 1-, 3-, and 5-year overall survival rates were 49%, 41%, and 38%, respectively. The main causes of death were infections (n = 21) and evolution of neoplasia (n = 6). In univariate analysis, the main detrimental prognostic factors identified were erythema multiforme-like skin lesions (P = .05) and histologic keratinocyte necrosis (P = .03). None of the 5 patients with Castleman disease died during the study. After adjustment for age and sex in multivariate analysis, erythema multiforme-like skin lesions remained predictive of fatal outcome, with a 2-fold increase in death rate (hazard ratio [HR], 2.3; 95% CI, 1.05-5.03; P = .04). The prognosis of patients with PNP was even poorer when erythema multiforme-like skin lesions were associated with severe skin or mucosal involvement at presentation (HR of death, 3.0; 95% CI, 1.01-8.92; P = .049). CONCLUSION Patients with PNP with erythema multiforme-like skin lesions and histologic keratinocyte necrosis, especially when associated with extensive lesions at presentation, are likely to have a more severe and rapid fatal outcome and should be managed very carefully.
Published: 2012

40. Cancer mortality study among French cement production workers

Author: Michel Aubier, Michel Rossignol, Jacques Benichou, William Dab, Alain Marconi, Lucien Abenhaim, Denis Zmirou-Navier, Danièle Luce, Philippe Clément, Chaire d'Hygiène et sécurité du travail, Conservatoire National des Arts et Métiers [CNAM] (CNAM), Laboratoire Modélisation, épidémiologie et surveillance des risques sanitaires (MESuRS), Department of Epidemiology, Biostatistics and Occupational Health [Montréal], McGill University = Université McGill [Montréal, Canada], Santé publique et épidémiologie des déterminants professionnels et sociaux de la santé, Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Unité de biostatistiques [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Lafarge Centre de Recherche [Lyon] (Lafarge LCR Lyon), Lafarge, Auteur indépendant, Physiopathologie et Epidemiologie de l'Insuffisance Respiratoire, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut National de la Santé et de la Recherche Médicale (INSERM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lafarge France [Groupe Holcim], McGill University, Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Unité de biostatistiques [Rouen], and Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Santé publique, MESH: Regression Analysis, MESH: Occupational Exposure, Cohort Studies, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, Neoplasms, Medicine, MESH: Neoplasms, MESH: Incidence, MESH: Cohort Studies, Cancer, MESH: Aged, education.field_of_study, Public health, MESH: Middle Aged, Mortality rate, Incidence, Middle Aged, 030210 environmental & occupational health, Occupational Diseases, MESH: Young Adult, 030220 oncology & carcinogenesis, 8. Economic growth, Cohort, Regression Analysis, Female, France, Cohort study, Adult, MESH: Occupational Diseases, medicine.medical_specialty, Portland cement, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Young Adult, Occupational Exposure, MESH: Construction Materials, Humans, education, Aged, Retrospective Studies, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, MESH: Humans, business.industry, Proportional hazards model, Construction Materials, Public Health, Environmental and Occupational Health, MESH: Adult, MESH: Retrospective Studies, Cement production, Confidence interval, MESH: Male, MESH: France, Standardized mortality ratio, Mortality study, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female, Demography
Abstract: International audience; PURPOSE: To analyse the mortality and its causes, especially cancer, among French cement production workers. METHODS: A cohort of all workers employed at least 1 year in one of the main four cement companies in France was assembled (9,118 workers, 122,124 person-years of follow-up between 1990 and 2005). A common job titles classification was used to analyse occupational risk factors. We conducted a standardized mortality ratio analysis based on age, gender and calendar-period-specific national mortality rates and explored the combined effect of job titles and duration through an internal Cox regression analysis. RESULTS: The number of deaths during the follow-up period was 430 (4.7%). Malignant neoplasm was the cause of 48.1% of deaths. Overall, a deficit in all-causes mortality (standardized mortality ratio (SMR): 0.68, 95% confidence interval (CI) 0.61-0.74) and in cancer mortality (SMR: 0.80, CI 0.69-0.92) was observed. Working in the quarry, yard and shipping sectors was associated with a 50% higher all-causes mortality risk in comparison with the administrative sector. CONCLUSIONS: This cohort study does not support previous observations that cement workers are at higher risk of cancer mortality than the general population. The length of follow-up should be increased, and specific exposures deserve analysis.
Published: 2011

41. Evaluation of the effects of a semi-automated vitrification performed before or after in vitro maturation (IVM) on the kinetic of oocyte maturation and chromosome segregation

Author: Marteil, Gaëlle, L, Chaput, Dollet, Sandra, PEREIRA, Bruno, Eymard-Pierre, Eléonore, Fiot, Melanie, Gouhier, Charlène, Gremeau, Anne Sophie, Chauffour, Candice, Tchirkov, Andrei, Brugnon, Florence, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), CHU Clermont-Ferrand, Centre d'Assistance Médicale à la Procréation [CHU Clermont-Ferrand] (AMP CECOS), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Service de Cytogénétique Médicale [CHU Clermont-Ferrand], European Society of Human Reproduction and Embryology (ESHRE), and Marteil, Gaëlle
Subjects: nuclear maturation, fertility preservation, oocyte vitrification, In vitro maturation, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology
Abstract: International audience; Study question:What are the optimal vitrification method (semi-automated vs. manual) and oocyte stage for in vitro-matured oocyte cryopreservation using meiosis kinetics and chromosome segregation as readouts?Summary answer:The semi-automated vitrification method does not impact oocyte nuclear maturation quality compared with the manual method. Immature oocyte cryopreservation should be performed after IVM.What is known already ?Fertility preservation using oocyte vitrification should be performed before oncological treatments. The reference protocol consists in collecting mature oocytes after ovarian stimulation. Nevertheless, ovarian stimulation sometimes yields immature oocytes or cannot be performed (e.g., emergency oncological treatment). An IVM step is therefore required but it is not clearly demonstrated whether IVM should be performed before or after vitrification. Oocyte vitrification is usually performed with manual methods. A semi-automated vitrification device (Gavi®, Genea Biomedx) showing high performances for embryo was recently released. To our knowledge, no study has analysed its efficiency on oocyte vitrification. Study design, size, duration:200 immature oocytes collected from ICSI cycles from January 2020 will be used. Oocytes will be divided in five groups (40 oocytes/group): freshly matured oocytes (group 1 control), oocytes vitrified after IVM by a manual technique (group 2a) or by Gavi® (group 2b) and oocytes vitrified prior IVM (groups 3a and 3b). We assess oocyte nuclear maturation quality by evaluating IVM kinetics by time-lapse (Geri®) and the accuracy of homologous chromosomes segregation by CGH array. Participants/materials, setting, methods:Since January 2020, 124 out of 200 immature oocytes have been included for this study. These oocytes provide from women under 37 years old without ovulatory disorder after signing an informed consent. The kinetics of meiotic resumption (germinal vesicle breakdown (GVBD) and polar body extrusion (PBE) timings), is determined by time-lapse technology (Geri®, Genea Biomedx). The accuracy of the homologous chromosome segregation during the first meiotic division will be assessed by CGH-Array. Main results and the role of chance:The clinico-biological characteristics (age, BMI, smoking and total FSH dose) are comparable between the five groups (p>0.05). No significant difference in post-thawing oocyte survival rate is observed between the two vitrification methods (semi-automated 58% vs. manual 64%). A significant difference in the overall oocyte survival rate is observed according to the stage of vitrification with a significantly higher survival rate if oocytes are vitrified at the mature stage (93% (2a+2b) vs. 61% (3a+3b), p =0.02). The IVM rate is significantly higher if oocytes are matured freshly (86% in group 1 (fresh IVM, n= 7) and 93% in group 2a+2b (IVM before vitrification, n= 27)) compared to post vitrification (71% in group 3a+3b, n= 28), p=0.03. The vitrification technique does not seem to impact IVM rate since it reached 64% (group 3a, n=11) and 76% (group 3b, n=16) (p=0.4). GVBD and PBE timings are not significantly different between the 5 groups, suggesting that neither the oocyte stage of vitrification nor the vitrification technique affects maturation kinetics. Similarly, our preliminary results of polar bodies and oocytes chromosomal profiles assessed by CGH-Array demonstrate a similar rate of aneuploidy (monosomy or trisomy) between the groups. Limitations, reasons for caution:Our preliminary results of CGH array should be confirmed with the analysis of a larger number of IVM oocytes. Wider implications of the findings:Vitrification of immature oocytes should be performed by semi-automated or manual methods after IVM. Tour knowledge, this is the first study comparing the efficiency of both semi-automated and manual vitrification methods on immature and in vitro-matured oocytes.Trial registration number: NCT03680937
Published: 2022

42. Clinical pregnancy rates of oocyte donor cycles are similar when universal media and/or oocyte-specific media are used for oocyte vitrification and warming

Author: Lafontaine, Maxime, Marteil, Gaëlle, Pereira, Bruno, Gouhier, Charlène, Vorilhon, Solène, Chaput, Laure, Chauffour, Candice, Valdeyron, Camille, Gremeau, Anne Sophie, Brugnon, Florence, Centre d'Assistance Médicale à la Procréation [CHU Clermont-Ferrand] (AMP CECOS), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), and Service de Gynécologie [CHU Clermont-Ferrand]
Subjects: [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, [SHS]Humanities and Social Sciences
Abstract: International audience
Published: 2022

43. Effectiveness of brief interventions in primary care for cannabis users aged from 12 to 25 years old: a systematic review

Author: Camille Chazal, Charline Roux, Shérazade Kinouani, Matthieu Schuers, Frédéric Fortin, Bruno Pereira, Olivier Blanc, Nathalie Piñol-Domenech, Georges Brousse, Philippe Vorilhon, Catherine Laporte, Faculté de Médecine - Clermont-Auvergne (FM - UCA), Université Clermont Auvergne (UCA), Université de Bordeaux (UB), 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 Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Rouen, Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, Institut Pascal (IP), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Bibliothèque Université Clermont Auvergne (BUCA), Service de Psychiatrie de l'Adulte B [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], and AutomédiCation aCcompagnement Pluriprofessionnel PatienT (ACCePPT)
Subjects: Adult, Adolescent, Primary Health Care, Motivational Interviewing, Primary care, Adolescents, Young Adult, Crisis Intervention, General practitioners, Humans, Emerging adults, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Brief interventions, Family Practice, Child, Cannabis, Randomized Controlled Trials as Topic
Abstract: Introduction The aim of this systematic review was to assess the effectiveness of brief interventions realized in primary care in reducing cannabis use for adolescents and emerging adults. Methods PubMed, CINAHL, Embase, PsycInfo, and Central (Cochrane Library) were searched until December 2020. Randomized controlled trials conducted in primary care, concerning in-person brief interventions for non-medical cannabis users aged from 12 to 25 years old were eligible for inclusion. Brief interventions had to last 30 min or less. Patients with comorbid mental health disorder or very specific populations were not included. Results One thousand eighty hundred and fifty-five studies were identified through database searching; only 8 studies involving 2,199 patients were included for qualitative synthesis after double reading and data extraction. Randomized controlled trials selected were heterogeneous regarding screening tools, initial levels of cannabis use and cannabis outcomes measures. Brief interventions were all based on motivational interviewing techniques or personalized feedback. Seven studies consisted in a single session of brief intervention. Six studies involved also other substance users. No significant reduction of cannabis use after brief intervention was found for most studies, especially in the long term. A trend of decreased cannabis consequences, such as negative psychosocial repercussions, perception of cannabis use by peers, or driving under the influence of cannabis, was reported. Conclusion The current state of knowledge does not allow us to say that the brief intervention is effective in reducing cannabis use among adolescents in primary care. We found a mild positive effect on cannabis consequences after brief intervention. Mixed qualitative and quantitative studies are need to better evaluate the impact of brief intervention and his faisability. PROSPERO (International Prospective Register of Systematic Reviews): n° CRD42016033080.
Published: 2022

44. Myopie et travail professionnel de près à l’âge adulte : revue systématique et méta-analyse

Author: Dutheil, Frédéric, Castanon, Joris, Maurin, Caroline, Mermillod, Martial, Chiambaretta, Frédéric, Clinchamps, Maëlys, Mondillon, Laurie, Lesage, François-Xavier, Pereira, Bruno, Navel, Valentin, Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Service Santé Travail Environnement [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service d'Ophtalmologie [CHU Clermont-Ferrand], Laboratoire de Psychologie et NeuroCognition (LPNC ), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Dynamique des capacités humaines et des conduites de santé (EPSYLON), Université Paul-Valéry - Montpellier 3 (UPVM), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Unité de Biostatistiques [CHU Clermont-Ferrand], and Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI)
Subjects: [SCCO.PSYC]Cognitive science/Psychology, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Crise sanitaire, 2020 reporté 2022.; International audience
Published: 2022

45. OntoBioStat: Supporting Causal Diagram Design and Analysis

Author: Thibaut Pressat Laffouilhère, Julien Grosjean, Jacques Bénichou, Stefan J. Darmoni, Lina F. Soualmia, Département d'Informatique Médicale (D2IM), CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Unité de biostatistiques [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Laboratoire d'Informatique, du Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, Mode de vie, génétique et santé : études intégratives et transgénérationnelles (U1018 (Équipe 9)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, and LEJEUNE, Emeline
Subjects: [STAT]Statistics [stat], Causality, Biometry, Variable selection, Bias, Ontology, Decision support techniques, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Biostatistics, Statistic, [STAT] Statistics [stat], [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract: International audience; Suitable causal inference in biostatistics can be best achieved by knowledge representation thanks to causal diagrams or directed acyclic graphs. However, necessary and sufficient causes are not easily represented. Since existing ontologies do not fill this gap, we designed OntoBioStat in order to enable covariate selection support based on causal relation representations. OntoBioStat automatic ontological causal diagram construction and inferences are detailed in this study. OntoBioStat inferences are allowed by Semantic Web Rule Language rules and axioms. First, statements made by the users include outcome, exposure, covariate, and causal relation specification. Then, reasoning enable automatic construction using generic instances of Meta_Variable and Necessary_Variable classes. Finally, inferred classes highlighted potential bias such as confounder-like. Ontological causal diagram built with OntoBioStat was compared to a standard causal diagram (without OntoBioStat) in a theoretical study. It was found that confounding and bias were not completely identified by the standard causal diagram, and erroneous covariate sets were provided. Further research is needed in order to make OntoBioStat more usable.
Published: 2022

46. Coxsackievirus A6 Recombinant Subclades D3/A and D3/H Were Predominant in Hand-Foot-And-Mouth Disease Outbreaks in the Paediatric Population, France, 2010–2018

Author: Stéphanie Tomba Ngangas, Maxime Bisseux, Gwendoline Jugie, Céline Lambert, Robert Cohen, Andreas Werner, Christine Archimbaud, Cécile Henquell, Audrey Mirand, Jean-Luc Bailly, Université Clermont Auvergne, CNRS, LMGE, 63000 Clermont–Ferrand, France, Service de Virologie Médicale et Moléculaire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Association Clinique et Thérapeutique Infantile du Val de Marne (ACTIV), Association Française de P ediatrie Ambulatoire (AFPA), and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-CH de Troyes
Subjects: Male, Sequence Analysis, DNA, atypical hand-foot-and-mouth disease, enterovirus surveillance, clinical epidemiology, molecular typing, third-generation sequencing, whole-genome sequencing, recombination, Disease Outbreaks, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Foot-and-Mouth Disease, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Animals, Humans, Female, Hand, Foot and Mouth Disease, Enterovirus
Abstract: International audience; Coxsackievirus A6 (CVA6) emerged as the most common enterovirus of seasonal outbreaks of hand-foot-and-mouth disease (HFMD). We investigated CVA6 genetic diversity among the clinical phenotypes reported in the paediatric population during sentinel surveillance in France between 2010 and 2018. CVA6 infection was confirmed in 981 children (mean age 1.52 years [IQR 1.17–2.72]) of whom 564 (58%) were males. Atypical HFMD was reported in 705 (72%) children, followed by typical HFMD in 214 (22%) and herpangina in 57 (6%) children. Throat specimens of 245 children were processed with a target-enrichment new-generation sequencing approach, which generated 213 complete CVA6 genomes. The genomes grouped within the D1 and D3 clades (phylogeny inferred with the P1 genomic region). In total, 201 genomes were classified among the recombinant forms (RFs) A, B, F, G, H, and N, and 12 genomes were assigned to 5 previously unreported RFs (R–V). The most frequent RFs were A (58%), H (19%), G (6.1%), and F (5.2%). The yearly number of RFs ranged between 1 (in 2012 and 2013) and 6 (2018). The worldwide CVA6 epidemic transmission began between 2005 and 2007, which coincided with the global spread of the recombinant subclade D3/RF-A.
Published: 2022
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47. Designing, Implementing, and Evaluating a Home-Based, Multidisciplinary, Family-Centered Pediatric Obesity Intervention: The ProxOb Program

Author: Magalie Miolanne, Céline Lambert, Julie Masurier, Charlotte Cardenoux, Alicia Fillion, Sarah Beraud, Chloé Desblés, Amélie Rigal, Elodie Védrine, Carla Dalmais, Bernadette Da Silva, Elisabeth De L’Eprevier, Juliette Hazart, Jean-Philippe Chaput, Vicky Drapeau, Bruno Pereira, Grace O’Malley, David Thivel, Yves Boirie, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Centre Auvergne de l'Obésité et de ses Risques en Santé (CALORIS), Laboratory of Metabolic Adaptations to Exercise in Physiological and Pathological Conditions, Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Direction de la Recherche Clinique et de l'Innovation [AP-HP] (DRCI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Childrens Hospital of Eastern Ontario, Unité de Biostatistiques [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Université Laval [Québec] (ULaval), Unité de Nutrition Humaine (UNH), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA)
Subjects: [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, family-based, home setting, pediatric obesity, prevention, treatment, Pediatrics, Perinatology and Child Health
Abstract: Although family-based interventions have been suggested as promising approaches for preventing and treating pediatric obesity, available studies failed to include the whole family in its own natural environment and routine. This paper aims to detail the development, implementation, and evaluation phases of the ProxOb home-based, family-centered program and present its feasibility and early results. ProxOb provides families with a 6-month multidisciplinary, home-based, and family-centered intervention followed by an 18-month maintenance phase. A global psychosocial, clinical, and behavior evaluation was conducted at baseline (T0) at the end of the 6-month intervention (T1) and after the 18-month maintenance phase (T2). A total of 130 families with at least one child with obesity completed the ProxOb program so far, and more than 90% of them also presented at least one parent with overweight or obesity. Being part of a single-parent family seemed to increase the chance of completing the intervention (63.0% vs. 33.3% in the drop-outers subgroup, p = 0.03). The BMI z-score for children with obesity (T0 = 4.38 ± 1.05; T1 = 4.06 ± 1.07; T2 = 4.29 ± 1.12) significantly decreased between T0 and T1, followed by weight regain at T2. ProxOb proposes a feasible and replicable real-life approach to address childhood obesity while involving the children’s family.
Published: 2022

48. Occupational Risk Factors by Sectors: An Observational Study of 20,000 Workers

Author: Luther Dogbla, Cédric Gouvenelle, Florence Thorin, François-Xavier Lesage, Marek Zak, Ukadike Chris Ugbolue, Barbara Charbotel, Julien S. Baker, Bruno Pereira, Frédéric Dutheil, Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Service Santé Travail Environnement [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Association de Prévention Santé au Travail du Cher ((APST18)), Activité, Connaissance, Transmission, éducation (ACTé ), Université Clermont Auvergne (UCA), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Jan Kochanowski University, University of the West of Scotland (UWS), Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement (UMRESTTE UMR_T9405), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Gustave Eiffel, Hong Kong Baptist University (HKBU), Unité de Biostatistiques [CHU Clermont-Ferrand], and Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI)
Subjects: Occupational health, sectors of activity, [SDV]Life Sciences [q-bio], Health, Toxicology and Mutagenesis, prevalence, Public Health, Environmental and Occupational Health, [SHS]Humanities and Social Sciences, Occupational Diseases, [STAT]Statistics [stat], Logistic Models, Risk Factors, Occupational Exposure, Surveys and Questionnaires, [SDE]Environmental Sciences, Work exposure, Self Report
Abstract: International audience; Objective: We aimed to assess the prevalence of exposure by sector and the sectors of activity most exposed to each exposure, using routine occupational health data, and to quantify the risk of being exposed. Method: Occupational risk factors were assessed by workers followed by the Occupational Health Service of Cher, using self-reported questionnaires. The sectors of activity were grouped into seven sectors, and the risks were grouped into six occupational exposure groups. Comparisons were made using the Chi-squared test and Cramer’s V, and the odds ratios were calculated by using logistic regression. Results: We included 19,891 workers. The construction sector had the highest prevalence (p < 0.05 vs. all other sectors) of exposure to physical (76%) and biomechanical factors (82%), as well as chemical risks (75%). Human health and social work was the sector with the highest prevalence of exposure to biological factors (69%), psychosocial factors (90%), and atypical working hours (61%). With workers from administrative and support sectors as the reference, construction workers had more chance of declaring exposure to physical factors (OR = 3.28, 95%CI = 2.89 to 3.72), biomechanical factors (1.82, 1.58 to 2.09), and chemical agents (3.83, 3.38 to 4.33). Workers from the human health and social sectors had more chance of being exposed to biological agents (13.4, 11.9 to 15.2), atypical working hours (1.93, 1.75 to 2.14), and psychosocial factors (2.74, 2.38 to 3.16). Conclusion: Psychosocial risk factors were commonly reported in all sectors. Workers in the construction, human health, and social sectors seem to report more exposures than those in other sectors. The analysis of occupational exposures is a necessary basis to build an efficient preventive strategy for occupational health.
Published: 2023

49. Cancer et environnement : expertise collective

Author: Isabelle Baldi, Denis Bard, Robert Barouki, Simone Benhamou, Jacques Bénichou, Marie-Odile Bernier, Olivier Bouchot, Pierre Carayon, Jocelyn Ceraline, Emmanuelle Charafe-Jauffret, Jacqueline Clavel, Françoise Clavel-Chapelon, Florent de Vathaire, Mariette Gerber, Anabelle Gilg Soit Ilg, Pascal Guenel, André Guillouzo, Pierre Hainaut, Marie-Claude Jaurand, Eric Jougla, Guy Launoy, Dominique Laurier, Yves Lévi, Marc Maynadie, Isabelle Momas, Jean-Claude Pairon, Christophe Paris, Claude Parmentier, Marc Sanson, Jean-François Savouret, Isabelle Stücker, Patrick Thonneau, Marie Walschaerts, Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, École des Hautes Études en Santé Publique [EHESP] (EHESP), Pharmacologie, toxicologie et signalisation cellulaire (U747), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Méthodologie statistique et épidémiologie génétique de maladies multifactorielles, Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR), Unité de biostatistiques [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Laboratoire d épidémiologie des rayonnements ionisants (IRSN/PSE-SANTE/SESANE/LEPID), Service de recherche sur les effets biologiques et Sanitaires des rayonnements ionisants (IRSN/PSE-SANTE/SESANE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Hôtel-Dieu de Nantes, Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), Progression tumorale et microenvironnement. Approches translationnelles et épidémiologie, Université de Strasbourg (UNISTRA)-CHU Strasbourg-Les Hôpitaux Universitaires de Strasbourg (HUS)-Institut Régional du Cancer-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), Centre de Recherche en Cancérologie de Marseille (CRCM / U891 Inserm), 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), Epidémiologie environnementale des cancers, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, hormones et cancer: épidémiologie et prévention (E3N), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie des cancers : Radiocarcinogénèse et effets iatrogènes des traitements, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLC Val d'Aurelle-Paul Lamarque, CRLCC Val d'Aurelle - Paul Lamarque, Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de Veille Sanitaire (INVS), Détoxication et réparation tissulaire, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre international de Recherche sur le Cancer (CIRC), Génomique fonctionnelle des tumeurs solides (U674), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'épidémiologie sur les causes médicales de décès (CépiDc), Cancers et Populations : Facteurs de Risque, Depistage, Pratiques Diagnostiques et Therapeutiques, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Laboratoire Santé Publique-Environnement [Chatenay-Malabry] (LSPE - UP-S), Université Paris Sud (Paris 11), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Epidémiologie Environnementale : Impact Sanitaire des Pollutions (EA 4064), Université Paris Descartes - Paris 5 (UPD5), Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Evaluations et prévention des risques professionnels et environnementaux [Nancy] (EPRPE - ERI11 Inserm), Cancéropôle du Grand Est-Université Henri Poincaré - Nancy 1 (UHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11), Biologie des Interactions Neurones / Glie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe de recherche en fertilité humaine ( GRFH), 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), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT), Service d'épidémiologie [Fontenay aux Roses], 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), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), ORANGE, Colette, Institut de Santé Publique, d'Epidémiologie et de Développement ( ISPED ), École des Hautes Études en Santé Publique [EHESP] ( EHESP ), Physiologie Cellulaire des Regulations Hormonales, Nutritionnelles et Pharmacologiques, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université d'Évry-Val-d'Essonne ( UEVE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Gustave Roussy ( IGR ), Unité de biostatistiques [Rouen], CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Institut de Radioprotection et de Sûreté Nucléaire ( IRSN ), Aix-Marseille Université - Faculté de médecine ( AMU MED ), Aix Marseille Université ( AMU ), Signalisation et Cancer de la Prostate, 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 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Nutrition, hormones et cancer: épidémiologie et prévention ( E3N ), Epidémiologie, sciences sociales, santé publique ( IFR 69 ), Université Panthéon-Sorbonne ( UP1 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École des hautes études en sciences sociales ( EHESS ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Panthéon-Sorbonne ( UP1 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École des hautes études en sciences sociales ( EHESS ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Veille Sanitaire, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Internationale de la recherche sur le cancer (CIRC), Génomique Fonctionnelle des Tumeurs Solides ( U1162 ), Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre d'épidémiologie sur les causes médicales de décès ( CépiDc ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire Santé Publique et Environnement, Université Paris Descartes - Paris 5 ( UPD5 ), Registre des hémopathies malignes de Côte d'Or, Institut Mondor de recherche biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Epidémiologie Environnementale : Impact Sanitaire des Pollutions ( EA 4064 ), Evaluations et prévention des risques professionnels et environnementaux, Cancéropôle du Grand Est-Université Henri Poincaré - Nancy 1 ( UHP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Toxicologie, Pharmacologie et Signalisation Cellulaire ( U1124 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Epidémiologie environnementale des cancers (Villejuif, Val de Marne), Equipe de recherche en fertilité humaine EA 3694 ( GRFH ), and Université Toulouse III - Paul Sabatier ( UPS )
Subjects: Tumeurs cérébrales, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Cancer de l'ovaire, Exposition aux agents chimiques et physiques, Cancer de la thyroïde, Mésothéliome, Hémopathies malignes, Cancer du testicule, Cancer de la prostate, [ SDV.EE.SANT ] Life Sciences [q-bio]/Ecology, environment/Health, Toxicité, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cancer du poumon, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Cancer du sein
Abstract: Les cancers représentent en France la première cause de mortalité chez les hommes et la deuxième cause chez les femmes et figurent parmi les pathologies pouvant être liées à l’environnement. À la demande de l’Afsset, l’Inserm a réuni un groupe d’experts afin d’établir un bilan des connaissances sur les liens entre l’exposition à des facteurs physiques, chimiques ou biologiques présents dans l’atmosphère, l’eau, les sols ou l’alimentation et neuf types de cancers en augmentation au cours des vingt-cinq dernières années : les cancers du poumon, les mésothéliomes, les hémopathies malignes, les tumeurs cérébrales, les cancers du sein, de l’ovaire, du testicule, de la prostate etde la thyroïde. Sont analysés dans cette expertise, les données épidémiologiquessur les différents cancers, les connaissances sur l’exposition aux facteurs environnementaux, les mécanismes de toxicité des polluants, les questions relatives à l’exposition aux faibles doses.
Published: 2008

50. Preventive treatment of allograft rejection after endothelial keratoplasty: A systematic review and meta‐analysis

Author: Florent Magnier, Frédéric Dutheil, Bruno Pereira, Stephanie L. Watson, Julien S. Baker, Frédéric Chiambaretta, Valentin Navel, Service d'Ophtalmologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Service Santé Travail Environnement [CHU Clermont-Ferrand], Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), The University of Sydney, Hong Kong Baptist University (HKBU), Génétique, Reproduction et Développement (GReD), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)
Subjects: Endothelium, Corneal, Fuchs' Endothelial Dystrophy, Visual Acuity, Glaucoma, General Medicine, Allografts, Corneal Diseases, Ophthalmology, Humans, Ocular Hypertension, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Descemet Membrane, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Descemet Stripping Endothelial Keratoplasty, Retrospective Studies
Abstract: International audience; urposeTo evaluate the efficacy of preventive treatment against allograft rejection after endothelial keratoplasty (EK), we conducted a systematic review and meta-analysis.MethodPubMed, Cochrane Library, Embase and ScienceDirect databases were searched until May 2021. We computed a random-effect meta-analysis on graft rejection rate stratified by the intervention (i.e. Descemet membrane EK (DMEK) and Descemet stripping (Automated) EK (DS(A)EK) or ultrathin (UT)-DSAEK), and postoperative treatment. Meta-regressions were performed to compare intervention, treatment and influence of putative confusion factors.ResultsWe included 49 studies and 12 893 EK (6867 DMEK and 6026 DS(A)EK/UT-DSAEK). Topical steroids were merged in two efficacy regimens: standard steroids (prednisolone acetate 1% or dexamethasone 0.1%) and soft steroids (fluorometholone 0.1% or loteprednol etabonate 0.5%). Globally, DMEK had a lower graft rejection rate than DS(A)EK/UT-DSAEK (coefficient − 3.3, 95 CI, −4.60 to −1.90; p
Published: 2022

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