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1. Interferential therapy for chronic constipation in adults: The CON‐COUR randomizedcontrolled trial

Author

Veronique Vitton, François Mion, Anne‐Marie Leroi, Charlène Brochard, Benoit Coffin, Frank Zerbib, Henri Damon, Chloé Melchior, Henri Duboc, Michel Queralto, Karine Baumstarck, Assistance Publique - Hôpitaux de Marseille (APHM), Hospices Civils de Lyon (HCL), Application des ultrasons à la thérapie (LabTAU), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU), Service de physiologie digestive, urinaire, respiratoire et de l'exercice [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d'Hépato-Gastroentérologie [CHU Rouen], and Service de Colo-proctologie, Clinique des Cèdres, Cornebarrieu, France

Subjects
Oncology, [SDV]Life Sciences [q-bio], Gastroenterology
Published
2023
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2. Efficacy and safety of combination targeted therapies in immune-mediated inflammatory disease: the COMBIO study

Author

Lucas Guillo, Benoit Flachaire, Jérôme Avouac, Catherine Dong, Maria Nachury, Guillaume Bouguen, Anthony Buisson, Ludovic Caillo, Mathurin Fumery, Cyrielle Gilletta, Xavier Hébuterne, Pierre Lafforgue, David Laharie, Emmanuel Mahé, Hubert Marotte, Stéphane Nancey, Sébastien Ottaviani, Jean-Hugues Salmon, Guillaume Savoye, Mélanie Serrero, Mathieu Uzzan, Manuelle Viguier, Christophe Richez, Laurent Peyrin-Biroulet, Philipe Seksik, Thao Pham, Philippe Ah-Soune, Nadia Arab, Laurent Beaugerie, Loïs Bolko, Joelle Bonnet, Yoram Bouhnik, Anne Bourrier, Franck Brazier, Franck Carbonnel, Maeva Charkaoui, Isabelle Charlot-Lambrecht, Antoine Chupin, Alice Combier, Marion Couderc, Fabienne Coury-Lucas, Ariadne Desjeux, Nicolas Duveau, Anne Grasland, Jean-Charles Grimaud, Xavier Guennoc, Cécilia Landman, Isabelle Nion-Larmurier, Catherien Leberre, Romain Leenhardt, Aude Le Goffic, Henri Montaudie, Jacques Morel, Thierry Passeron, Jeanne-Marie Perotin Collard, Elodie Poisnel, Vincent Pradel, Martin Soubrier, Harry Sokol, Eric Toussirot, Caroline Trang, My-Linh Trans Minh, Sophie Trijau, Frank Verhoeven, Stéphanie Viennot, Daniel Wendling, Hôpital Nord [CHU - APHM], Rhumatologie [Sainte- Marguerite - APHM] ( Hôpitaux Sud), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépato-gastro-entérologie [APHP Kremlin-Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU 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), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), 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, CHU Amiens-Picardie, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Nice (CHU Nice), Institut du Mouvement et de l’appareil Locomoteur [Hôpital Sainte-Marguerite - APHM] (IML), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-Rhumatologie [Sainte- Marguerite - APHM] ( Hôpitaux Sud), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre Hospitalier Victor Dupouy, Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier Universitaire de Reims (CHU Reims), Vieillissement, Fragilité (VIEFRA - EA 3797), Université de Reims Champagne-Ardenne (URCA), Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpital Beaujon [AP-HP], Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Hôpital universitaire Robert Debré [Reims], Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Service de Rhumatologie [CHU Pellegrin], Groupe hospitalier Pellegrin, Centre National de Référence des Maladies Auto-Immunes Systémiques Rares de l'Est et du Sud-Ouest (RESO), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Centre International de Recherche en Infectiologie - UMR (CIRI), 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), and Hôpital Charles Nicolle [Rouen]-CHU Rouen

Subjects
Adult, Cohort Studies, Immunomodulating Agents, Crohn Disease, Immune-mediated inflammatory diseases, Hepatology, Gastroenterology, Humans, Tumor Necrosis Factor Inhibitors, Ustekinumab, Molecular targeted therapy, Combination therapy, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; BACKGROUND: Use of a combination of targeted therapies (COMBIO) in patients with refractory/overlapping immune-mediated inflammatory diseases (IMIDs) has increased, but reported data remain scarce. We aimed to assess effectiveness and safety of COMBIO in patients with IMIDs. METHODS: We conducted a French ambispective multicenter cohort study from September 2020 to May 2021, including adults' patients with 1 or 2 IMIDs and treated at least 3-month with COMBIO. RESULTS: Overall, 143 patients were included. The most common IMIDs were Crohn's disease (63.6%), axial spondyloarthritis (37.7%), and ulcerative colitis (14%). Half of patients had only one IMID, of which 60% were Crohn's disease. Mean duration of COMBIO was 274.5±59.3 weeks, and COMBIO persistence at 104 weeks was estimated at 64.1%. The most frequent COMBIOs combined anti-TNF agents with vedolizumab (30%) or ustekinumab (28.7%). Overall, 50% of patients achieved significant and 27% mild-to-moderate improvement in patient-reported outcomes. Extended duration of COMBIO (aOR=1.09; 95% CI: 1.03-1.14; p=0.002) and diagnoses of two IMIDs (aOR=3.46; 95%CI: 1.29-9.26; p=0.013) were associated with significant improvement in patient-reported outcomes. Incidence of serious infection during COMBIO was 4.51 per 100 person-years (95% CI 2.20-8.27) and 5 COMBIOs were discontinued due to adverse events. CONCLUSIONS: COMBIO can be effective and safe in patients with refractory/overlapping IMIDs.

Published
2023
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3. Increased Risk of Cancer and Mortality in a Large French Population-Based Paediatric-Onset Inflammatory Bowel Disease Retrospective Cohort

Author

Dupont-Lucas, Claire, Leroyer, Ariane, Ley, Delphine, Spyckerelle, Claire, Bertrand, Valérie, Turck, Dominique, Savoye, Guillaume, Maunoury, Vincent, Guillon, Nathalie, Fumery, Mathurin, Sarter, Hélène, Gower-Rousseau, Corinne, Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Pédiatrie Médicale [Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Lille, Université de Lille, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Division de Gastroenterologie, Hepatologie et Nutrition, Departement de Pediatrie, Hôpital Jeanne de Flandre Lille, Hôpital St Vincent de Paul, Groupe Hospitalier du Havre Hôpital Jacques Monod (MONTIVILLIERS) (GHH), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpital Claude Huriez [Lille], Service d'Epidémiologie et de Santé Publique [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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, and CHU Amiens-Picardie

Subjects
Crohn’s disease, cohort study, Gastroenterology, General Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, ulcerative colitis
Abstract

Background and Aims Paediatric-onset IBD [pIBD] is associated with an increased risk of cancer and mortality in adulthood. The aims of this study were to measure the incidence of cancer and mortality in patients with pIBD and identify factors associated with mortality and cancer. Methods All patients diagnosed with Crohn’s disease [CD] or ulcerative colitis [UC] before the age of 17 years between 1988 and 2011 in the EPIMAD registry were retrospectively followed until 2013 for cancer and 2015 for mortality. Standardized incidence [SIR] and mortality ratios [SMR] were estimated compared to the general population. Cox regression was used to compare the effect of exposures on cancer and mortality among IBD patients. Results We included 1344 patients [52% males, 75% CD], totalling 12 957 patient-years for cancer incidence and 18 817 patient-years for mortality. There were 14 cases of cancer [median age 27.8 years] and 15 deaths [median age 28.8 years]. The incidence of cancer and of mortality were increased compared to the general population: all-cancer SIR = 2.7 (95% confidence interval [CI]: 1.5–4.8), SMR = 1.7 [95% CI: 1.0–2.8]. Colorectal cancer had the highest SIR and SMR: SIR = 41.2 [95% CI: 17.2–99.0], SMR = 70.4 [95% CI 22.7–218.2]. Cancer was associated with (hazard ratio [HR], 95% CI): active smoking at diagnosis [5.5, 1.8–16.5], p = 0.002; any exposure to anti-tumour necrosis factor [6.1, 1.7–22.3], p = 0.0065; and exposure to combination therapy [7.4, 1.8–29.7], p = 0.0047. Mortality was associated with extraintestinal manifestations (HR 4.9 [95% CI: 1.7–13.8], p = 0.003). Conclusions In this large population-based cohort, patients with pIBD had an increased risk of both cancer [2.7-fold] and mortality [1.7-fold], particularly for colorectal cancer.

Published
2022
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4. Natural History of Anal Ulcerations in Pediatric-Onset Crohn's Disease: Long-Term Follow-Up of a Population-Based Study

Author

Perrine Mortreux, Ariane Leroyer, Claire Dupont, Delphine Ley, Valérie Bertrand, Claire Spyckerelle, Nathalie Guillon, Pauline Wils, Corinne Gower-Rousseau, Guillaume Savoye, Mathurin Fumery, Dominique Turck, Laurent Siproudhis, Hélène Sarter, CHU Lille, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Pédiatrie Médicale [Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Le Havre, Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL), Centre Hospitalier Universitaire de Reims (CHU Reims), Normandie Université (NU), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Service d'hépato-gastro-entérologie [Rennes] = Gastroenterology [Rennes], CHU Pontchaillou [Rennes], Hôpital St Vincent de Paul, Service d'Epidémiologie et de Santé Publique [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), and Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie

Subjects
Hepatology, [SDV]Life Sciences [q-bio], Gastroenterology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Background: Anal ulcerations are frequently observed in Crohn's disease (CD). However, their natural history remains poorly known, especially in pediatric-onset CD.Methods: All patients with a diagnosis of CD before the age of 17 years between 1988 and 2011 within the population-based registry EPIMAD were followed retrospectively until 2013. At diagnosis and during follow-up, the clinical and therapeutic features of perianal disease were recorded. An adjusted time-dependent Cox model was used to evaluate the risk of evolution of anal ulcerations towards suppurative lesions.Results: Among the 1,005 included patients (females, 450 (44.8%); median age at diagnosis 14.4 years (IQR, 12.0-16.1)), 257 (25.6%) had an anal ulceration at diagnosis. Cumulative incidence of anal ulceration at 5 and 10 years from diagnosis was 38.4% (CI95%, 35.2-41.4) and 44.0% (CI95%, 40.5-47.2), respectively. In multivariable analysis, the presence of extra-intestinal manifestations (Hazard Ratio (HR) 1.46, CI95% 1.19-1.80, p=0.0003) and upper digestive location (HR 1.51, CI95% 1.23-1.86, p

Published
2023
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5. Long-term effectiveness and safety of anti-TNF in pediatric-onset inflammatory bowel diseases: A population-based study

Author

Mathurin Fumery, Claire Dupont, Delphine Ley, Guillaume Savoye, Valérie Bertrand, Nathalie Guillon, Pauline Wils, Corinne Gower-Rousseau, Helene Sarter, Dominique Turck, Ariane Leroyer, 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, CHU Amiens-Picardie, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Groupe Hospitalier du Havre Hôpital Jacques Monod (MONTIVILLIERS) (GHH), Service d'Epidémiologie et de Santé Publique [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and CHU Lille

Subjects
Crohn's disease, Hepatology, Ulcerative colitis, Gastroenterology, anti-TNF, Primary non-response, Loss of response, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Background: Anti-TNF agents are the first biologic treatment option in inflammatory bowel disease (IBD). The long-term effectiveness of this strategy at the population level is poorly known, particularly in pediatric-onset IBD.Methods: All patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) before the age of 17 between 1988 and 2011 in the EPIMAD population-based registry were followed retrospectively until 2013. Among patients treated with anti-TNF, the cumulative probabilities of anti-TNF failure defined by primary failure, loss of response (LOR) or intolerance were evaluated. Factors associated with anti-TNF failure were investigated by a Cox model.Results: Among a total of 1,007 patients with CD and 337 patients with UC, respectively 481 (48%) and 81 (24%) were treated with anti-TNF. Median age at anti-TNF initiation was 17.4 years (IQR, 15.1-20.9). Median duration of anti-TNF therapy was 20.4 months (IQR, 6.0-59.9). In CD, the probability of failure of 1st line anti-TNF at 1, 3 and 5 years was respectively 30.7%, 51.3% and 61.9% for infliximab and 25.9%, 49.3% and 57.7% for adalimumab (p = 0.740). In UC, the probability of failure of 1st line anti-TNF therapy was respectively 38.4%, 52.3% and 72.7% for infliximab and 12.5% for these 3 timepoints for adalimumab (p = 0.091). The risk of failure was maximal in the first year of treatment and LOR was the main reason for discontinuation. Female gender was associated with LOR (HR, 1.48; 95%CI 1.02-2.14) and with anti-TNF withdrawal for intolerance in CD (HR, 2.31; 95%CI 1.30-4.11) and disease duration (≥ 2 y vs. < 2 y) was associated with LOR in UC (HR, 0.37; 95%CI 0.15-0.94) in multivariate analysis. Sixty-three (13.5%) patients observed adverse events leading to termination of treatment (p = 0.57). No death, cancer or tuberculosis was observed while the patients were under anti-TNF treatment.Conclusion: In a population-based study of pediatric-onset IBD, about 60% in CD and 70% in UC experienced anti-TNF failure within 5 years. Loss of response account for around two-thirds of failure, both for CD and UC.

Published
2023
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6. Transanal irrigation is a better choice for bowel dysfunction in adults with spina bifida: a randomized controlled trial

Author

Charlène Brochard, Magali Jezequel, Anne Blanchard‐Dauphin, Jacques Kerdraon, Brigitte Perrouin‐Verbe, Anne‐Marie Leroi, Jean Michel Reymann, Benoît Peyronnet, Jeff Morçet, Laurent Siproudhis, CHU Pontchaillou [Rennes], The Enteric Nervous System in gut and brain disorders [U1235] (TENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), CHU Lille, Centre Mutualiste de Kerpape, Ploemeur, Centre hospitalier universitaire de Nantes (CHU Nantes), Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de physiologie digestive, urinaire, respiratoire et de l'exercice [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'urologie [Rennes] = Urology [Rennes], Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service des Maladies de l'Appareil Digestif [CHU Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-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 French Ministry of Health. Grant Number: 2013-A01520-45

Subjects
transanal irrigation, faecal incontinence, [SDV]Life Sciences [q-bio], Gastroenterology, bowel dysfunction, conservative treatment, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Spina bifida, randomised controlled trial
Abstract

International audience; Aim: To compare transanal irrigation with conservative bowel management for the treatment of bowel dysfunction in Spina bifida (SB) patients.Methods: Patients with SB and bowel dysfunction were randomly assigned to receive either transanal irrigation or conservative bowel management. The effectiveness of the treatment was defined as a decrease of 4 points in the neurogenic bowel dysfunction (NBD) score at week 10. Data on incontinence (Cleveland scores; Jorge-Wexner [JW]) and constipation (Knowles-Eccersley-Scott Symptom Constipation Score [KESS]) were recorded at 10 and 24 weeks after inclusion. Data were analysed on an intention-to-treat basis.Results: A total of 34 patients were randomised: 16 patients to conservative bowel management and 18 patients to transanal irrigation. A total of 19/31 (61%) patients improved at week 10, 13 (76%) in the transanal irrigation group versus six (43%) in the conservative group (p = 0.056). In the irrigation group, the decrease in NBD score was -6.9 (-9.9 to -4.02) versus -1.9 (-6.5 to -2.8) in the conservative group (p = 0.049 in univariate and p = 0.004 in multivariate analysis). The NBD, Cleveland (JW and KESS) and Rosenberg scores were significantly lower in the transanal irrigation group than in the conservative bowel management group at week 10.Conclusions: This prospective, randomised, controlled, multicentre study in adult patients with SB suggests that transanal irrigation may be more effective than conservative bowel management.

Published
2023
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7. Associations between postprandial symptoms, hydrogen and methane production, and transit time in irritable bowel syndrome

Author

Joost P. Algera, Esther Colomier, Chloé Melchior, Jóhann P. Hreinsson, Irina Midenfjord, Egbert Clevers, Magnus Simrén, Hans Törnblom, douville, sabine, University of Gothenburg (GU), Technologie campus Gent - KU Leuven (KU Leuven), Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Normandie Université (NU), and University of North Carolina at Chapel Hill (UNC)

Subjects
colonic fermentation, Physiology, Clinical Neurology, QUESTIONNAIRE, INTESTINAL BACTERIAL OVERGROWTH, MICROENVIRONMENT, ABDOMINAL-PAIN, IBS, CARBOHYDRATE, MOTILITY, gastrointestinal transit, symptom assessment, Science & Technology, Gastroenterology & Hepatology, Endocrine and Autonomic Systems, Neurosciences, SOMATIZATION, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, DEPRESSION, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, GASTROINTESTINAL TRANSIT, visceral hypersensitivity, Neurosciences & Neurology, SENSITIVITY, Life Sciences & Biomedicine
Abstract

BACKGROUND: Abnormal oroanal transit time (OATT) and visceral hypersensitivity are key pathophysiological factors in irritable bowel syndrome (IBS). The lactulose nutrient challenge test (LNCT) has been developed to assess the postprandial symptoms and gut microbial fermentation. We aimed to investigate associations between OATT, rectal sensitivity, and LNCT in IBS patients. METHODS: We included 263 IBS patients from two study cohorts, where the link between pathophysiology and symptoms was investigated. During the LNCT, severity of postprandial symptoms was graded, and breath hydrogen/methane concentrations were measured after ingestion of a combined lactulose nutrient drink every 15 min for 4 h. The patients underwent rectal sensitivity (rectal barostat) and OATT (radiopaque markers) investigations. Comorbid conditions (functional dyspepsia, anxiety, depression, and somatization) were assessed with questionnaires. KEY RESULTS: After controlling for comorbid conditions, rectal sensitivity was associated with abdominal pain (p

Published
2022
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8. P155 Natural history of anal stricture in pediatric-onset Crohn’s disease: a two-decades population-based study

Author

Mortreux, P, Leroyer, A, Ley, D, Dupont-Lucas, C, Bertrand, V, Wils, P, Coevoet, H, Paupard, T, Gower-Rousseau, C, Siproudhis, L, Guillon, N, Sarter, H, Savoye, G, Turck, D, Fumery, Mathurin, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Jeanne de Flandre [Lille], Université de Lille, Groupe Hospitalier du Havre, Hôpital privé Arras les Bonnettes, Registre EPIMAD, CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Amiens-Picardie-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), SFNCP, GREP, IHFIH UPRES EA 3859, Centre d'Études Biologiques de Chizé - UMR 7372 (CEBC), La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), and Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie

Subjects
Gastroenterology, General Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background The natural history of anal stricture complicating pediatric-onset Crohn’s disease (CD) is poorly known. The aims of this study were: to determine in a population-based study the risk of anal stricture in pediatric-onset CD; to identify risk factors for anal stricture; and to evaluate the natural history of anal stricture at the population level. Methods All patients with a diagnosis of CD made before the age of 17 years between 1988 and 2011 in a population-based registry were followed retrospectively until 2013. A specific collection of additional data was performed in patients with anal stricture at diagnosis or during follow-up. Variables collected included: proctological examination, diagnostic management and treatment. Multivariate Cox models were used to identify factors associated with anal stricture. Results Among the 1,007 included CD patients (females, 451 (44.8%); median age at diagnosis 14.4 years (IQR, 12.0-16.1), median follow-up 8.8 years (IQR, 4.6-14.2)), only one (0.1%) had anal stricture at diagnosis while 26 (2.6%) presented anal stricture during follow-up. Cumulative incidence of anal stricture at 5 and 10 years after diagnosis was 0.6% (CI95%, 0.1-1.1) and 1.4% (CI95%, 0.5-2.3), respectively. Among the 27 patients with anal stricture, 25 (92.6%) had already at least one episode of anal ulceration or fistulizing perianal CD (pCD). In multivariable analysis, the presence of extra-intestinal manifestations (Hazard Ratio (HR) 2.2, CI95% 1.0-4.8, p=0.027), colonic location (L1 vs L3 HR 0.0 (-); L2 vs L3 HR 1.2, CI95% 0.6-2.7, p=0.006) and history of fistulizing pCD (HR 9.9, CI95% 4.3-22.8, p Conclusion Anal stricture is a rare event in pediatric onset CD, occurring in 1.5% of patients over a 10 year-period after diagnosis. However, anal stricture had a negative impact on disease prognosis with a five-fold increase of the risk of stoma.

Published
2023
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9. Fatty acids produced by the gut microbiota dampen host inflammatory responses by modulating intestinal SUMOylation

Author

Chaima Ezzine, Léa Loison, Nadine Montbrion, Christine Bôle-Feysot, Pierre Déchelotte, Moïse Coëffier, David Ribet, Ribet, David, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de nutrition [CHU Rouen], CHU Rouen, and Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN)

Subjects
Microbiology (medical), Gut microbiota, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], host-bacteria interactions, Microbiology, Branched Chain Fatty Acids (BCFAs), Ubiquitin-like proteins, intestinal inflammation, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], post-translational modifications, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Inflammation, Short Chain Fatty Acids (SCFAs), Bacteria, Microbiota, Fatty Acids, Gastroenterology, Sumoylation, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Fatty Acids, Volatile, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Gastrointestinal Microbiome, Intestines, Infectious Diseases, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

International audience; The gut microbiota produces a wide variety of metabolites, which interact with intestinal cells and contribute to host physiology. The effect of gut commensal bacteria on host protein SUMOylation, an essential ubiquitin-like modification involved in various intestinal functions, remains, however, unknown. Here, we show that short chain fatty acids (SCFAs) and branched chain fatty acids (BCFAs) produced by the gut microbiota increase protein SUMOylation in intestinal cells in a pH-dependent manner. We demonstrate that these metabolites inactivate intestinal deSUMOylases and promote the hyperSUMOylation of nuclear matrix-associated proteins. We further show that BCFAs inhibit the NF-κB pathway, decrease pro-inflammatory cytokine expression, and promote intestinal epithelial integrity. Together, our results reveal that fatty acids produced by gut commensal bacteria regulate intestinal physiology by modulating SUMOylation and illustrate a new mechanism of dampening of host inflammatory responses triggered by the gut microbiota.

Published
2022
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10. Overlaps with bladder pain syndrome and irritable bowel syndrome are associated with higher symptom burden and reduced quality of life in functional dyspepsia

Author

Fabien Wuestenberghs, Maximilien Baron, Chloé Melchior, Charlotte Desprez, Jean‐Nicolas Cornu, Anne‐Marie Leroi, Guillaume Gourcerol, Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), CHU UCL Namur, Service d'urologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Service de physiologie digestive, urinaire, respiratoire et de l'exercice [CHU Rouen], Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), UCL - (MGD) Service de gastro-entérologie, and UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie

Subjects
irritable bowel syndrome, symptom burden, Endocrine and Autonomic Systems, Physiology, digestive, oral, and skin physiology, Gastroenterology, Cystitis, Interstitial, functional dyspepsia, digestive system diseases, Irritable Bowel Syndrome, quality of life, Sleep Initiation and Maintenance Disorders, Surveys and Questionnaires, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Prevalence, Quality of Life, Humans, bladder pain syndrome, Dyspepsia, ComputingMilieux_MISCELLANEOUS
Abstract

Functional dyspepsia and bladder pain syndrome are well-known to overlap with irritable bowel syndrome. Whether functional dyspepsia overlaps with bladder pain syndrome remains unknown. Our aim was to evaluate the presence of bladder pain syndrome in functional dyspepsia patients and its impact. All consecutive patients with investigated dyspeptic symptoms in our tertiary care center between March 2015 and November 2018 were studied. Functional dyspepsia and irritable bowel syndrome were diagnosed according to Rome III and IV criteria while bladder pain syndrome was diagnosed using ESSIC criteria. Validated questionnaires were filled to assess quality of life (GIQLI), anxiety and depression (HADS), sleep (PSQI), and insomnia (ISI). Dyspeptic symptoms severity was assessed individually for eight dyspeptic complaints. Among 1453 patients with dyspeptic symptoms, 61.4% fulfilled Rome criteria for functional dyspepsia. Bladder pain syndrome was present in 16.0% of the patients not fulfilling diagnostic criteria for functional dyspepsia, 22.2% of patients with functional dyspepsia alone, and 36.4% of patients with overlapping functional dyspepsia and irritable bowel syndrome (p-values

Published
2022
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11. Irritable bowel syndrome: Factors of importance for disease-specific quality of life

Author

Chloé Melchior, Esther Colomier, Inês A. Trindade, Mahrukh Khadija, Jóhann P. Hreinsson, Hans Törnblom, Magnus Simrén, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Department of Chronic Diseases, Metabolism and Aging (CHROMETA), Translational Research Center for Gastrointestinal Disorders (TARGID), Leuven, Belgium., UNC Center for Functional GI and Motility Disorders, University of North Carolina, Chapel Hill, NC, USA., and douville, sabine

Subjects
Adult, Male, SYMPTOMS, IMPACT, Gastrointestinal Diseases, Severity of Illness Index, disease-specific QOL, VISCERAL SENSITIVITY, Irritable Bowel Syndrome, Young Adult, IBS, ANXIETY, Humans, VALIDITY, disease-specific quality of life, irritable bowel syndrome, QOL, Science & Technology, Gastroenterology & Hepatology, Depression, factors, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Middle Aged, SLEEP, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, IBSQOL, SEVERITY, Medically Unexplained Symptoms, Oncology, quality of life, COPING STRATEGIES, Quality of Life, Female, Life Sciences & Biomedicine, SEXUAL DYSFUNCTION
Abstract

BACKGROUND: Irritable bowel syndrome patients report reduced disease-specific quality of life (IBSQOL). Factors of potential relevance for QOL include gastrointestinal (GI), psychological, and somatic symptoms, demographics, and GI motor and sensory abnormalities. OBJECTIVE: The aim of our study was to evaluate the relative importance of these factors on the different IBSQOL dimensions. METHODS: We included irritable bowel syndrome (IBS) patients who completed validated questionnaires to assess QOL, stool form and frequency, GI symptom severity, psychological distress, GI-specific anxiety, sense of coherence, and overall somatic symptom severity. Patients also underwent tests for oroanal transit time and rectal sensitivity. The nine dimensions of IBSQOL and their average (overall IBSQOL) were used as outcome variables, and factors associated with these were assessed using general linear models. RESULTS: We included 314 IBS patients (74% female, mean age 36.3 ± 12.2 years). Higher stool frequency, GI and overall somatic symptom severity, psychological distress, and GI-specific anxiety were independently associated with reduced overall IBSQOL, with the model explaining 60% of the variance (p

Published
2022
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12. Clinical outcomes after treatment with direct antiviral agents: beyond the virological response in patients with previous HCV-related decompensated cirrhosis

Author

Pageaux, G. (Georges-Philippe), Nzinga, C. (Clovis Lusivika), Ganne, N. (Nathalie), Samuel, D. (Didier), Dorival, C. (Céline), Zoulim, F. (Fabien), Cagnot, C. (Carole), Decaens, T. (Thomas), Thabut, D. (Dominique), Asselah, T. (Tarik), Mathurin, P. (Philippe), Habersetzer, F. (Francois), Bronowicki, J. (Jean-Pierre), Guyader, D. (Dominique), Rosa, I. (Isabelle), Leroy, V. (Vincent), Chazouilleres, O. (Olivier), de Ledinghen, V. (Victor), Bourliere, M. (Marc), Causse, X. (Xavier), Cales, P. (Paul), Metivier, S. (Sophie), Loustaud-Ratti, V. (Véronique), Riachi, G. (Ghassan), Alric, L. (Laurent), Gelu-Simeon, M. (Moana), Minello, A. (Anne), Gournay, J. (Jérôme), Geist, C. (Claire), Tran, A. (Albert), Abergel, A. (Armand), Portal, I. (Isabelle), d'Alteroche, L. (Louis), Raffi, F. (François), Fontaine, H. (Hélène), Carrat, F. (Fabrice), Pol, S. (Stanislas), Baumert, Thomas F., Doffoel, M. (Michel), Mutter, C. (Catherine), Simo-Noumbissie, P. (Pauline), Razi, E. (Esma), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), 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), Physiopathogénèse et Traitement des Maladies du Foie, Hôpital Paul Brousse-Université Paris-Saclay, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Physiopathologie des Maladies Inflammatoires de l'Intestin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Interactions Virus-Hôte et Maladies Hépatiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Virologie, Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHI Créteil, Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint-Joseph [Marseille], Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université d'Angers (UA), CHU Toulouse [Toulouse], Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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), Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, 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), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), French ANRS CO22 Hepather Cohort: Delphine Bonnet, Virginie Payssan-Sicart, Chloe Pomes, François Bailly, Marjolaine Beaudoin, Dominique Giboz, Kerstin Hartig-Lavie, Marianne Maynard, Eric Billaud, David Boutoille, Morane Cavellec, Caroline Chevalier, Isabelle Hubert, Pierre Goepfert, Adrien Lannes, Françoise Lunel, Jérôme Boursier, Nathalie Boyer, Nathalie Giuily, Corinne Castelnau, Giovanna Scoazec, Aziza Chibah, Sylvie Keser, Karim Bonardi, Anaïs Vallet-Pichard, Philippe Sogni, Juliette Foucher, Jean-Baptiste Hiriart, Amandine Legendre, Faiza Chermak, Marie Irlès-Depé, Si Nafa Si Ahmed, Christelle Ansaldi, Nisserine Ben Amara, Valérie Oules, Jacqueline Dunette, Rodolphe Anty, Eve Gelsi, Régine Truchi, Elena Luckina, Nadia Messaoudi, Joseph Moussali, Barbara De Dieuleveult, Héloïse Goin, Damien Labarrière, Pascal Potier, Si Nafa Si Ahmed, Véronique Grando-Lemaire, Pierre Nahon, Séverine Brulé, Rym Monard, Caroline Jezequel, Audrey Brener, Anne Laligant, Aline Rabot, Isabelle Renard, Thomas F Baumert, Michel Dofföel, Catherine Mutter, Pauline Simo-Noumbissie, Esma Razi, Hélène Barraud, Mouni Bensenane, Abdelbasset Nani, Sarah Hassani-Nani, Marie-Albertine Bernard, Georges-Philippe Pageaux, Michael Bismuth, Ludovic Caillo, Stéphanie Faure, Marie Pierre Ripault, Christophe Bureau, Sarah Launay, Jean Marie Peron, Marie Angèle Robic, Léa Tarallo, Marine Faure, Bruno Froissart, Marie-Noelle Hilleret, Jean-Pierre Zarski, Odile Goria, Victorien Grard, Hélène Montialoux, Muriel François, Christian Ouedraogo, Christelle Pauleau, Anne Varault, Tony Andreani, Bénédicte Angoulevant, Azeline Chevance, Lawrence Serfaty, Teresa Antonini, Audrey Coilly, Jean-Charles Duclos Vallée, Mariagrazia Tateo, Corinne Bonny, Chanteranne Brigitte, Géraldine Lamblin, Léon Muti, Abdenour Babouri, Virginie Filipe, Camille Barrault, Laurent Costes, Hervé Hagège, Soraya Merbah, Paul Carrier, Maryline Debette-Gratien, Jérémie Jacques, Guillaume Lassailly, Florent Artu, Valérie Canva, Sébastien Dharancy, Alexandre Louvet, Marianne Latournerie, Marc Bardou, Thomas Mouillot, Yannick Bacq, Didier Barbereau, Charlotte Nicolas, Caroline Chevalier, Isabelle Archambeaud, Sarah Habes, Nisserine Ben Amara, Danièle Botta-Fridlund, Eric Saillard, Marie-Josée Lafrance, Carole Cagnot, Alpha Diallo, Lena Wadouachi, Ventzi Petrov-Sanchez, Douae Ammour, Loubna Ayour, Jaouad Benhida, Fabrice Carrat, Frederic Chau, Céline Dorival, Audrey Gilibert, Isabelle Goderel, Warda Hadi, Clovis Luzivika Nzinga, Grégory Pannetier, François Pinot, Odile Stahl, François Téloulé, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Jonchère, Laurent

Subjects
Liver Cirrhosis, medicine.medical_specialty, Carcinoma, Hepatocellular, Survival, Hepatocellular carcinoma, [SDV]Life Sciences [q-bio], Decompensated cirrhosis, Infectious and parasitic diseases, RC109-216, Hepacivirus, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, complications, drug therapy, Gastroenterology, Antiviral Agents, Virological response, Internal medicine, Medicine, Humans, In patient, business.industry, Hepatitis C virus, Research, Liver Neoplasms, Hepatitis C, [SDV] Life Sciences [q-bio], Sustained virological response, Infectious Diseases, Direst-acting antiviral agents, therapeutic use, business, After treatment
Abstract

Background In HCV-infected patients with advanced liver disease, the direct antiviral agents-associated clinical benefits remain debated. We compared the clinical outcome of patients with a previous history of decompensated cirrhosis following treatment or not with direct antiviral agents from the French ANRS CO22 HEPATHER cohort. Methods We identified HCV patients who had experienced an episode of decompensated cirrhosis. Study outcomes were all-cause mortality, liver-related or non-liver-related deaths, hepatocellular carcinoma, liver transplantation. Secondary study outcomes were sustained virological response and its clinical benefits. Results 559 patients met the identification criteria, of which 483 received direct antiviral agents and 76 remained untreated after inclusion in the cohort. The median follow-up time was 39.7 (IQR: 22.7–51) months. After adjustment for multivariate analysis, exposure to direct antiviral agents was associated with a decrease in all-cause mortality (HR 0.45, 95% CI 0.24–0.84, p = 0.01) and non-liver-related death (HR 0.26, 95% CI 0.08–0.82, p = 0.02), and was not associated with liver-related death, decrease in hepatocellular carcinoma and need for liver transplantation. The sustained virological response was 88%. According to adjusted multivariable analysis, sustained virological response achievement was associated with a decrease in all-cause mortality (HR 0.29, 95% CI 0.15–0.54, p Conclusion Treatment with direct antiviral agents is associated with reduced risk for mortality. The sustained virological response was 88%. Thus, direct antiviral agents treatment should be considered for any patient with HCV-related decompensated cirrhosis. Trial registration: ClinicalTrials.gov registry number: NCT01953458.

Published
2022
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13. Identification of bacterial lipopeptides as key players in IBS

Author

Camille Petitfils, Sarah Maurel, Gaelle Payros, Amandine Hueber, Bahija Agaiz, Géraldine Gazzo, Rémi Marrocco, Frédéric Auvray, Geoffrey Langevin, Jean-Paul Motta, Pauline Floch, Marie Tremblay-Franco, Jean-Marie Galano, Alexandre Guy, Thierry Durand, Simon Lachambre, Anaëlle Durbec, Hind Hussein, Lisse Decraecker, Justine Bertrand-Michel, Abdelhadi Saoudi, Eric Oswald, Pierrick Poisbeau, Gilles Dietrich, Chloe Melchior, Guy Boeckxstaens, Matteo Serino, Pauline Le Faouder, Nicolas Cenac, SEGUIN, Nathalie, APPEL À PROJETS GÉNÉRIQUE 2018 - Les lipopeptides produits par le microbiote : de l'hypersensibilité à la thérapie dans le syndrome de l'intestin irritable - - LiBacPain2018 - ANR-18-CE14-0039 - AAPG2018 - VALID, Signalisation des lipides du microbiote sur l'hôte - - MILI2020 - ANR-20-CE14-0011 - AAPG2020 - VALID, Ecole Universitaire de Recherche Interdisciplinaire sur la Douleur - - EURIDOL2017 - ANR-17-EURE-0022 - EURE - VALID, Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation - - METABOHUB2011 - ANR-11-INBS-0010 - INBS - VALID, Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées - - ANINFIMIP2011 - ANR-11-EQPX-0003 - EQPX - VALID, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaToul Lipidomics, MetaboHUB-MetaToul, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-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 Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Université de Montpellier (UM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Metatoul AXIOM (E20 ), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of Gothenburg (GU), Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Federation pour la Recherche sur le Cerveau (FRC) FRC20200411001, Centre National de la Recherche Scientifique. PP and GG received support from CNRS and University of Strasbourg. GG, CP and SM received a scholarship from Ministere de l'Enseignement Superieur, de la YRecherche et de l'Innovation., ANR-18-CE14-0039,LiBacPain,Les lipopeptides produits par le microbiote : de l'hypersensibilité à la thérapie dans le syndrome de l'intestin irritable(2018), ANR-20-CE14-0011,MILI,Signalisation des lipides du microbiote sur l'hôte(2020), ANR-17-EURE-0022,EURIDOL,Ecole Universitaire de Recherche Interdisciplinaire sur la Douleur(2017), ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011), and ANR-11-EQPX-0003,ANINFIMIP,Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées(2011)

Subjects
VISCERAL HYPERSENSITIVITY, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, IRRITABLE-BOWEL-SYNDROME, IRRITABLE BOWEL SYNDROME, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, ENTERIC BACTERIAL MICROFLORA, PRENATAL STRESS, INTESTINAL MICROBIOTA, LACTIC ACID BACTERIA, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BC] Life Sciences [q-bio]/Cellular Biology, CLOSTRIDIUM-CLOSTRIDIOFORME, RISK, Science & Technology, Gastroenterology & Hepatology, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, SEVERITY, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Life Sciences & Biomedicine, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, LIPIDS
Abstract

ObjectivesClinical studies revealed that early-life adverse events contribute to the development of IBS in adulthood. The aim of our study was to investigate the relationship between prenatal stress (PS), gut microbiota and visceral hypersensitivity with a focus on bacterial lipopeptides containing γ-aminobutyric acid (GABA).DesignWe developed a model of PS in mice and evaluated, in adult offspring, visceral hypersensitivity to colorectal distension (CRD), colon inflammation, barrier function and gut microbiota taxonomy. We quantified the production of lipopeptides containing GABA by mass spectrometry in a specific strain of bacteria decreased in PS, in PS mouse colons, and in faeces of patients with IBS and healthy volunteers (HVs). Finally, we assessed their effect on PS-induced visceral hypersensitivity.ResultsPrenatally stressed mice of both sexes presented visceral hypersensitivity, no overt colon inflammation or barrier dysfunction but a gut microbiota dysbiosis. The dysbiosis was distinguished by a decreased abundance ofLigilactobacillus murinus, in both sexes, inversely correlated with visceral hypersensitivity to CRD in mice. An isolate from this bacterial species produced several lipopeptides containing GABA including C14AsnGABA. Interestingly, intracolonic treatment with C14AsnGABA decreased the visceral sensitivity of PS mice to CRD. The concentration of C16LeuGABA, a lipopeptide which inhibited sensory neurons activation, was decreased in faeces of patients with IBS compared with HVs.ConclusionPS impacts the gut microbiota composition and metabolic function in adulthood. The reduced capacity of the gut microbiota to produce GABA lipopeptides could be one of the mechanisms linking PS and visceral hypersensitivity in adulthood.

Published
2022
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14. Bladder-colon chronic cross-sensitization involves neuro-glial pathways in male mice

Author

Karim Atmani, Fabien Wuestenberghs, Maximilien Baron, Illona Bouleté, Charlène Guérin, Wafa Bahlouli, David Vaudry, Jean Claude do Rego, Jean-Nicolas Cornu, Anne-Marie Leroi, Moïse Coëffier, Mathieu Meleine, Guillaume Gourcerol, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (MGD) Service de gastro-entérologie, Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU), CHU UCL Namur, Service de physiologie digestive, urinaire, respiratoire et de l'exercice [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Service d'urologie [Rouen], Cancer and Brain Genomics (CBG), Service Commun d'Analyse Comportementale (SCAC), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-High-tech Research Infrastructures for Life Sciences (HeRacLeS), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de nutrition [CHU Rouen], Neuro-Dol (Neuro-Dol), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)

Subjects
Male, Inflammation, [SDV]Life Sciences [q-bio], Urinary Bladder, Green Fluorescent Proteins, Gastroenterology, CX3C Chemokine Receptor 1, Pain, General Medicine, Rats, NK1 receptor, Rats, Sprague-Dawley, Mice, Inbred C57BL, Mice, Spinal Cord, Animals, Microglia, MAPK-p38, Colorectal Neoplasms, Proto-Oncogene Proteins c-fos, Cross-organ sensitization, Visceral hypersensitivity
Abstract

Irritable bowel syndrome and bladder pain syndrome often overlap and are both characterized by visceral hypersensitivity. Since pelvic organs share common sensory pathways, it is likely that those syndromes involve a cross-sensitization of the bladder and the colon. The precise pathophysiology remains poorly understood. To develop a model of chronic bladder-colon cross-sensitization and to investigate the mech-anisms involved. Chronic cross-organ visceral sensitization was obtained in C57BL/6 mice using ultrasound-guided intravesical injections of acetic acid under brief isoflurane anesthesia. Colorectal sensitivity was assessed in conscious mice by measuring intracolonic pressure during isobaric colorectal distensions. Myeloperoxidase, used as a marker of colorectal inflammation, was measured in the colon, and colorectal permeability was measured using chambers. c-Fos protein expression, used as a marker of neuronal activation, was assessed in the spinal cord (L6-S1 level) using immunohistochemistry. Green fluorescent protein on the fractalkine receptor-positive mice were used to identify and count microglia cells in the L6-S1 dorsal horn of the spinal cord. The expression of NK1 receptors and MAPK-p38 were quantified in the spinal cord using western blot. Visceral hypersensitivity to colorectal distension was observed after the intravesical injection of acetic acid saline ( < 0.0001). This effect started 1 h post-injection and lasted up to 7 d post-injection. No increased permeability or inflammation was shown in the bladder or colon 7 d post-injection. Visceral hypersensitivity was associated with the increased expression of c-Fos protein in the spinal cord ( < 0.0001). In green fluorescent protein on the fractalkine receptor-positive mice, intravesical acetic acid injection resulted in an increased number of microglia cells in the L6-S1 dorsal horn of the spinal cord ( < 0.0001). NK1 receptor and MAPK-p38 levels were increased in the spinal cord up to 7 d after injection ( = 0.007 and 0.023 respectively). Colorectal sensitization was prevented by intrathecal or intracerebroventricular injections of minocycline, a microglia inhibitor, by intracerebroventricular injection of CP-99994 dihydrochloride, a NK1 antagonist, and by intracerebroventricular injection of SB203580, a MAPK-p38 inhibitor. We describe a new model of cross-organ visceral sensitization between the bladder and the colon in mice. Intravesical injections of acetic acid induced a long-lasting colorectal hypersensitivity to distension, mediated by neuroglial interactions, MAPK-p38 phosphorylation and the NK1 receptor.

Published
2022
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15. Comparative Real-World Effectiveness of Vedolizumab and Ustekinumab for Patients with Ulcerative Colitis: A GETAID Multicentre Cohort Study

Author

Antoine Meyer, Mathurin Fumery, Laurent Peyrin-Biroulet, Jérôme Filippi, Romain Altwegg, Yoram Bouhnik, Melanie Serrero, David Laharie, Xavier Roblin, Maria Nachury, Vered Abitbol, Guillaume Cadiot, Stephane Nancey, Matthieu Allez, Cyrielle Gilletta, Lucine Vuitton, Guillaume Savoye, Stephane Nahon, Anne Bourrier, Anthony Buisson, Guillaume Bouguen, Arnaud Bourreille, Stephanie Viennot, Franck Carbonnel, Aurelien Amiot, Service d'Hépato-gastro-entérologie [APHP Kremlin-Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), 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, CHU Amiens-Picardie, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Nice (CHU Nice), University Hospital of Montpellier, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Nord [CHU - APHM], CHU Saint-Etienne, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Robert Debré, Hospices Civils de Lyon (HCL), Hopital Saint-Louis [AP-HP] (AP-HP), CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, Service de Gastroentérologie et nutrition [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Clermont-Ferrand, Nutrition, Métabolismes et Cancer (NuMeCan), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Nantes (CHU Nantes), Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Aix Marseille Université (AMU), CRHU Nancy, and CHU Bordeaux [Bordeaux]

Subjects
Cohort Studies, Treatment Outcome, Gastrointestinal Agents, Remission Induction, Gastroenterology, Humans, Ustekinumab, Colitis, Ulcerative, Tumor Necrosis Factor Inhibitors, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Retrospective Studies
Abstract

International audience; INTRODUCTION: There are currently no comparative data on the efficacy and safety of vedolizumab and ustekinumab in ulcerative colitis (UC) after anti-TNF therapy fails. METHODS: We retrieved the full datasets of two observational, multicentre, retrospective studies of patients with UC for whom anti-TNF therapy failed and the patients were then treated with either vedolizumab or ustekinumab. The outcomes included steroid-free clinical remission, clinical remission, treatment persistence, colectomy, hospitalization, and serious and infectious adverse events. Propensity scores weighted comparison was applied. RESULTS: In total, 121 patients were included in the vedolizumab group and 97 were included in the ustekinumab group. At week 14 and week 52, in the weighted cohort, no difference was found between vedolizumab and ustekinumab for steroid-free clinical remission (OR = 0.55 [0.21-1.41], p\,=\,.21 and 0.94 [0.40-2.22], p\,=\,.89, respectively). There was no difference between vedolizumab and ustekinumab for secondary outcomes such as clinical remission, hospitalization, UC-related surgery, treatment persistence and serious and infectious adverse events. CONCLUSION: In patients with UC for whom anti-TNF therapy failed, no difference was found between vedolizumab and ustekinumab after propensity scores weighted comparison. Further studies are required to determine predictive factors of the efficacy of both biological agents.

Published
2022
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16. Prediction of hepatocellular carcinoma in Hepatitis C patients with advanced fibrosis after sustained virologic response

Author

Azzi, Jessica, Dorival, Céline, Cagnot, Carole, Fontaine, Hélène, Lusivika-Nzinga, Clovis, Leroy, Vincent, de Ledinghen, Victor, Tran, Albert, Zoulim, Fabien, Alric, Laurent, Gournay, Jérôme, Bronowicki, Jean-Pierre, Decaens, Thomas, Riachi, Ghassan, Mikhail, Nabiel, Soliman, Reham, Shiha, Gamal, Pol, Stanislas, Carrat, Fabrice, Ganne-Carrié, Nathalie, Hepather, Anrs-Afef, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), ANRS France Recherche Nord & sud Sida-hiv hépatites, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Hospices Civils de Lyon, Departement de Neurologie (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre hospitalier universitaire de Nantes (CHU Nantes), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire [Grenoble] (CHU), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Assiut University, Port Said University, Mansoura University [Egypt], Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), AP-HP - Hôpitaux Universitaires Paris Seine-Saint-Denis (GHU 93), INSERM U1053, Université Bordeaux, Bordeaux, France., Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Purpan (CHU Purpan), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Inserm U1254, Centre Hospitalier Universitaire de Nancy (CHU Nancy), Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt, Biostatistics and Cancer Epidemiology Department, South Egypt Cancer Institute, Assiut University, Assuit, Egypt., Tropical Medicine Department, Faculty of Medicine, Port Said University, Port Said, Egypt., Hepatology and Gastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), École pratique des hautes études (EPHE), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC)

Subjects
Liver Cirrhosis, Male, Carcinoma, Hepatocellular, Hepatology, Sustained Virologic Response, Hepatitis C virus, Liver Neoplasms, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hepacivirus, Hepatitis C, Chronic, Middle Aged, Antiviral Agents, Hepatitis C, Risk factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Risk score, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, HCC, ComputingMilieux_MISCELLANEOUS
Abstract

International audience; Background & Aims: Prediction of hepatocellular carcinoma (HCC) occurrence in patients with chronic hepatitis C (HCV) who achieved a sustained virological response (SVR) after direct acting antivirals (DAAs) remains challenging.Methods: Among HCC-free HCV patients with advanced fibrosis enrolled in the ANRS CO22 HEPATHER cohort who achieved SVR 12 weeks after treatment with DAAs, HCC predictive models were developed using Cox multivariable regression. The derived score was externally validated in a large Egyptian cohort. Our main outcome was the HCC-free survival.Results: During follow-up (median 3.05 years), 153 out of 3531 patients developed a HCC. Main variables associated with HCC occurrence were: male gender, HCV genotype 3, esophageal varices, albumin < 40 g/L, total bilirubin >11 µmol/L and hypercholesterolemia before DAA initiation, together with age > 58 years, FIB-4 index ≥3.25 evaluated at SVR. A score was established allowing the stratification of patients by high (score ≥ 12/22), intermediate (7 ≤ score

Published
2022
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17. A European Survey on Digestive Perianastomotic Ulcerations, a Rare Crohn-like Disorder Occurring in Children and Young Adults

Author

Christos Tzivinikos, Ibrahim Shamasneh, Marina Aloi, Patrizia Alvisi, Erasmo Miele, Rémi Duclaux-Loras, Jérôme Viala, Stéphanie Willot, Rosa Lima, Claire Dupont-Lucas, Mario Mašić, Julie Lemale, Daniela Prlenda-Touilleux, J. Languepin, Sanja Kolaček, Chrystèle Madre, Alexandre Fabre, Kaija-Leena Kolho, Charlotte Bergoin, Sibylle Koletzko, Jean-Pierre Hugot, Raphaël Enaud, Christine Martinez-Vinson, Maria Nachury, Alexis Mosca, Annecarin Brueckner, Emmanuelle Dugelay, Hôpital Robert Debré, University of Zagreb, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Dr von Hauner Children's Hospital [Munich, Germany], Ludwig-Maximilians-Universität München (LMU), Service de pédiatrie multidisciplinaire [Hôpital de la Timone Enfants - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centro Hospitalar do Porto, CHU Bordeaux [Bordeaux], Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Geriatrics Unit [Pierre-Bénite], Université de Lyon-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Ospedale Maggiore Carlo Alberto Pizzardi di Bologna, Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Naples Federico II = Università degli studi di Napoli Federico II, Hospices Civils de Lyon (HCL), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Limoges, Service de Neuropédiatrie et Handicaps, Hôpital Gatien de Clocheville, CHU Tours, Université de Caen Normandie (UNICAEN), Normandie Université (NU), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Pédiatrie Médicale [Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Al Jalila Children's Specialty Hospital, Medical Genetics Unit, Shaare Zedek Medical Center, Hevrew University Medical School, Clinicum, Children's Hospital, HUS Children and Adolescents, Madre, Chrystele, Mašić, Mario, Prlenda-Touilleux, Daniela, Brueckner, Annecarin, Koletzko, Sibylle, Fabre, Alexandre, Viala, Jérome, Lima, Rosa, Enaud, Raphael, Lemale, Julie, Kolho, Kaija-Leena, Bergoin, Charlotte, Martinez-Vinson, Christine, Dugelay, Emmanuelle, Alvisi, Patrizia, Aloi, Marina, Miele, Erasmo, Duclaux-Loras, Remi, Nachury, Maria, Languepin, Jane, Willot, Stephanie, Dupont-Lucas, Claire, Mosca, Alexi, Tzivinikos, Christo, Shamasneh, Ibrahim, Kolaček, Sanja, and Hugot, Jean-Pierre

Subjects
Male, intestinal resection, Abdominal pain, Pediatrics, Hirschsprung disease, Inflammatory bowel disease, 0302 clinical medicine, 3123 Gynaecology and paediatrics, Interquartile range, 030212 general & internal medicine, Child, Digestive System Surgical Procedures, Anastomosis, Surgical, Gastroenterology, Crohn disease, COMPLICATION, Short bowel syndrome, 3. Good health, Failure to thrive, Necrotizing enterocolitis, Female, digestive perianastomotic ulcerations, 030211 gastroenterology & hepatology, gut inflammation, medicine.symptom, ileocaecal valve, medicine.medical_specialty, RESECTION, short bowel syndrome, Anastomosis, Young Adult, 03 medical and health sciences, Bloating, medicine, Humans, enteral nutrition, ANEMIA, Ulcer, necrotizing enterocolitis, business.industry, Infant, Newborn, Infant, ANASTOMOTIC ULCERS, abdominal surgery, medicine.disease, 3121 General medicine, internal medicine and other clinical medicine, Pediatrics, Perinatology and Child Health, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, INFLAMMATORY-BOWEL-DISEASE
Abstract

International audience; Objectives: Digestive perianastomotic ulcerations (DPAU) resembling Crohn disease lesions are long-term complications of intestinal resections, occurring in children and young adults. They are known to be uncommon, severe and difficult to treat.Methods: In the absence of recommendations, we performed a large European survey among the members of the ESPGHAN working group on inflammatory bowel disease (IBD) in order to collect the experience of expert pediatric gastroenterologists on DPAU.Results: Fifty-one patients (29 boys and 22 girls) were identified from 19 centers in 8 countries. Most patients were followed after necrotizing enterocolitis (n = 20) or Hirschsprung disease (n = 11). The anastomosis was performed at a median age (interquartile range) of 6 [1–23] months, and first symptoms occurred 39 [22–106] months after surgery. Anemia was the most prevalent symptom followed by diarrhea, abdominal pain, bloating, and failure to thrive. Hypoalbuminemia, elevated CRP, and fecal calprotectin were common. Deep ulcerations were found in 59% of patients usually proximally to the anastomosis (68%). During a median follow-up of 40 [19–67] months, treatments reported to be the most effective included exclusive enteral nutrition (31/35, 88%), redo anastomosis (18/22, 82%), and alternate antibiotic treatment (37/64, 58%).Conclusions: Unfortunately, persistence of symptoms, failure to thrive, and abnormal laboratory tests at last follow-up in most of patients show the burden of DPAU lacking optimal therapy and incomplete understanding of the pathophysiology.

Published
2021
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