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1. Detection of Ulcerative Colitis Lesions from Weakly Annotated Colonoscopy Videos Using Bounding Boxes

Author: Safaa Al-Ali, John Chaussard, Sébastien Li-Thiao-Té, Éric Ogier-Denis, Alice Percy-du-Sert, Xavier Treton, and Hatem Zaag
Subjects: bleeding, bounding box annotation, lesion detection, model selection, sensitivity, ulcer, Medicine, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Ulcerative colitis is a chronic disease characterized by bleeding and ulcers in the colon. Disease severity assessment via colonoscopy videos is time-consuming and only focuses on the most severe lesions. Automated detection methods enable fine-grained assessment but depend on the training set quality. To suit the local clinical setup, an internal training dataset containing only rough bounding box annotations around lesions was utilized. Following previous works, we propose to use linear models in suitable color spaces to detect lesions. We introduce an efficient sampling scheme for exploring the set of linear classifiers and removing trivial models i.e., those showing zero false negative or positive ratios. Bounding boxes lead to exaggerated false detection ratios due to mislabeled pixels, especially in the corners, resulting in decreased model accuracy. Therefore, we propose to evaluate the model sensitivity on the annotation level instead of the pixel level. Our sampling strategy can eliminate up to 25% of trivial models. Despite the limited quality of annotations, the detectors achieved better performance in comparison with the state-of-the-art methods. When tested on a small subset of endoscopic images, the best models exhibit low variability. However, the inter-patient model performance was variable suggesting that appearance normalization is critical in this context.
Published: 2024
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2. Systemically delivered adipose stromal vascular fraction mitigates radiation-induced gastrointestinal syndrome by immunomodulating the inflammatory response through a CD11b+ cell-dependent mechanism

Author: Lydia Bensemmane, Fabien Milliat, Xavier Treton, and Christine Linard
Subjects: Stromal vascular fraction, Intestine, Irradiation, Monocyte, Medicine (General), R5-920, Biochemistry, QD415-436
Abstract: Abstract Background Stromal vascular fraction (SVF) treatment promoted the regeneration of the intestinal epithelium, limiting lethality in a mouse model of radiation-induced gastrointestinal syndrome (GIS). The SVF has a heterogeneous cell composition; the effects between SVF and the host intestinal immunity are still unknown. The specific role of the different cells contained in the SVF needs to be clarified. Monocytes–macrophages have a crucial role in repair and monocyte recruitment and activation are orchestrated by the chemokine receptors CX3CR1 and CCR2. Methods Mice exposed to abdominal radiation (18 Gy) received a single intravenous injection of SVF (2.5 × 106 cells), obtained by enzymatic digestion of inguinal fat tissue, on the day of irradiation. Intestinal immunity and regeneration were evaluated by flow cytometry, RT-PCR and histological analyses. Results Using flow cytometry, we showed that SVF treatment modulated intestinal monocyte differentiation at 7 days post-irradiation by very early increasing the CD11b+Ly6C+CCR2+ population in the intestine ileal mucosa and accelerating the phenotype modification to acquire CX3CR1 in order to finally restore the F4/80+CX3CR1+ macrophage population. In CX3CR1-depleted mice, SVF treatment fails to mature the Ly6C−MCHII+CX3CR1+ population, leading to a macrophage population deficit associated with proinflammatory environment maintenance and defective intestinal repair; this impaired SVF efficiency on survival. Consistent with a CD11b+ being involved in SVF-induced intestinal repair, we showed that SVF-depleted CD11b+ treatment impaired F4/80+CX3CR1+macrophage pool restoration and caused loss of anti-inflammatory properties, abrogating stem cell compartment repair and survival. Conclusions These data showed that SVF treatment mitigates the GIS-involving immunomodulatory effect. Cooperation between the monocyte in SVF and the host monocyte defining the therapeutic properties of the SVF is necessary to guarantee the effective action of the SVF on the GIS.
Published: 2023
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3. The Appendix Orchestrates T-Cell Mediated Immunosurveillance in Colitis-Associated CancerSummary

Author: Maxime K. Collard, Julien Tourneur-Marsille, Mathieu Uzzan, Miguel Albuquerque, Maryline Roy, Anne Dumay, Jean-Noël Freund, Jean-Pierre Hugot, Nathalie Guedj, Xavier Treton, Yves Panis, and Eric Ogier-Denis
Subjects: Appendectomy, Appendicitis, Ulcerative Colitis, Inflammatory Bowel Disease, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background & Aims: Although appendectomy may reduce colorectal inflammation in patients with ulcerative colitis (UC), this surgical procedure has been suggested to be associated with an increased risk of colitis-associated cancer (CAC). Our aim was to explore the mechanism underlying the appendectomy-associated increased risk of CAC. Methods: Five-week-old male BALB/c mice underwent appendectomy, appendicitis induction, or sham laparotomy. They were then exposed to azoxymethane/dextran sodium sulfate (AOM/DSS) to induce CAC. Mice were killed 12 weeks later, and colons were taken for pathological analysis and immunohistochemistry (CD3 and CD8 staining). Human colonic tumors from 21 patients with UC who underwent surgical resection for CAC were immunophenotyped and stratified according to appendectomy status. Results: Whereas appendectomy significantly reduced colitis severity and increased CAC number, appendicitis induction without appendectomy led to opposite results. Intratumor CD3+ and CD8+ T-cell densities were lower after appendectomy and higher after appendicitis induction compared with the sham laparotomy group. Blocking lymphocyte trafficking to the colon with the anti-α4β7 integrin antibody or a sphingosine-1-phosphate receptor agonist suppressed the inducing effect of the appendectomy on tumors’ number and on CD3+/CD8+ intratumoral density. CD8+ or CD3+ T cells isolated from inflammatory neo-appendix and intravenously injected into AOM/DSS-treated recipient mice increased CD3+/CD8+ T-cell tumor infiltration and decreased tumor number. In UC patients with a history of appendectomy, intratumor CD3+ and CD8+ T-cell densities were decreased compared with UC patients without history of appendectomy. Conclusions: In UC, appendectomy could suppress a major site of T-cell priming, resulting in a less efficient CAC immunosurveillance.
Published: 2023
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4. The Heterochromatin protein 1 is a regulator in RNA splicing precision deficient in ulcerative colitis

Author: Jorge Mata-Garrido, Yao Xiang, Yunhua Chang-Marchand, Caroline Reisacher, Elisabeth Ageron, Ida Chiara Guerrera, Iñigo Casafont, Aurelia Bruneau, Claire Cherbuy, Xavier Treton, Anne Dumay, Eric Ogier-Denis, Eric Batsché, Mickael Costallat, Gwladys Revêchon, Maria Eriksson, Christian Muchardt, and Laurence Arbibe
Subjects: Science
Abstract: This study reports reduced expression of the chromatin and splicing regulator HP1γ in inflammatory bowel disease (IBD) and shows that HP1γ protects against pervasive RNA splicing leading to toxic mRNA products detected in IBD, like progerin.
Published: 2022
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5. Fecal microbiota and bile acids in IBD patients undergoing screening for colorectal cancer

Author: Aonghus Lavelle, Stéphane Nancey, Jean-Marie Reimund, David Laharie, Philippe Marteau, Xavier Treton, Matthieu Allez, Xavier Roblin, Georgia Malamut, Cyriane Oeuvray, Nathalie Rolhion, Xavier Dray, Dominique Rainteau, Antonin Lamaziere, Emilie Gauliard, Julien Kirchgesner, Laurent Beaugerie, Philippe Seksik, Laurent Peyrin-Biroulet, and Harry Sokol
Subjects: Gut microbiota, inflammatory bowel disease, dysplasia, colitis-associated colorectal cancer, crohn’s disease, ulcerative colitis, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Due to the potential role of the gut microbiota and bile acids in the pathogenesis of both inflammatory bowel disease (IBD) and sporadic colorectal cancer, we aimed to determine whether these factors were associated with colorectal cancer in IBD patients. 215 IBD patients and 51 non-IBD control subjects were enrolled from 10 French IBD centers between September 2011 and July 2018. Fecal samples were processed for bacterial 16S rRNA gene sequencing and bile acid profiling. Demographic, clinical, endoscopic, and histological outcomes were recorded. Characteristics of IBD patients included: median age: 41.6 (IQR 22); disease duration 13.2 (13.1); 47% female; 21.9% primary sclerosing cholangitis; 109 patients with Crohn’s disease (CD); 106 patients with ulcerative colitis (UC). The prevalence of cancer was 2.8% (6/215: 1 CD; 5 UC), high-grade dysplasia 3.7% (8/215) and low-grade dysplasia 7.9% (17/215). Lachnospira was decreased in IBD patients with cancer, while Agathobacter was decreased and Escherichia-Shigella increased in UC patients with any neoplasia. Bile acids were not associated with cancer or neoplasia. Unsupervised clustering identified three gut microbiota clusters in IBD patients associated with bile acid composition and clinical features, including a higher risk of neoplasia in UC in two clusters when compared to the third (relative risk (RR) 4.07 (95% CI 1.6–10.3, P
Published: 2022
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6. Impact of panelists’ experience on script concordance test scores of medical students

Author: Olivier Peyrony, Alice Hutin, Jennifer Truchot, Raphaël Borie, David Calvet, Adrien Albaladejo, Yousrah Baadj, Pierre-Emmanuel Cailleaux, Martin Flamant, Clémence Martin, Jonathan Messika, Alexandre Meunier, Mariana Mirabel, Victoria Tea, Xavier Treton, Sylvie Chevret, David Lebeaux, and Damien Roux
Subjects: Script concordance test, Medical student, Panelist, Special aspects of education, LC8-6691, Medicine
Abstract: Abstract Background The evaluation process of French medical students will evolve in the next few years in order to improve assessment validity. Script concordance testing (SCT) offers the possibility to assess medical knowledge alongside clinical reasoning under conditions of uncertainty. In this study, we aimed at comparing the SCT scores of a large cohort of undergraduate medical students, according to the experience level of the reference panel. Methods In 2019, the authors developed a 30-item SCT and sent it to experts with varying levels of experience. Data analysis included score comparisons with paired Wilcoxon rank sum tests and concordance analysis with Bland & Altman plots. Results A panel of 75 experts was divided into three groups: 31 residents, 21 non-experienced physicians (NEP) and 23 experienced physicians (EP). Among each group, random samples of N = 20, 15 and 10 were selected. A total of 985 students from nine different medical schools participated in the SCT examination. No matter the size of the panel (N = 20, 15 or 10), students’ SCT scores were lower with the NEP group when compared to the resident panel (median score 67.1 vs 69.1, p
Published: 2020
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7. A Preclinical Validation of Iron Oxide Nanoparticles for Treatment of Perianal Fistulizing Crohn’s Disease

Author: Antoine Cazelles, Maxime K. Collard, Yoann Lalatonne, Sabrina Doblas, Magaly Zappa, Camélia Labiad, Dominique Cazals-Hatem, Léon Maggiori, Xavier Treton, Yves Panis, Ulrich Jarry, Thomas Desvallées, Pierre-Antoine Eliat, Raphaël Pineau, Laurence Motte, Didier Letourneur, Teresa Simon-Yarza, and Eric Ogier-Denis
Subjects: Crohn’s disease, perianal fistula, preclinical model, iron oxide nanoparticles, fistula treatment, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Fistulizing anoperineal lesions are severe complications of Crohn’s disease (CD) that affect quality of life with a long-term risk of anal sphincter destruction, incontinence, permanent stoma, and anal cancer. Despite several surgical procedures, they relapse in about two-thirds of patients, mandating innovative treatments. Ultrasmall particles of iron oxide (USPIO) have been described to achieve in vivo rapid healing of deep wounds in the skin and liver of rats thanks to their nanobridging capability that could be adapted to fistula treatment. Our main purpose was to highlight preclinical data with USPIO for the treatment of perianal fistulizing CD. Twenty male Sprague Dawley rats with severe 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-induced proctitis were operated to generate two perianal fistulas per rat. At day 35, two inflammatory fistulas were obtained per rat and perineal magnetic resonance imaging (MRI) was performed. After a baseline MRI, a fistula tract was randomly drawn and topically treated either with saline or with USPIO for 1 min (n = 17 for each). The rats underwent a perineal MRI on postoperative days (POD) 1, 4, and 7 and were sacrificed for pathological examination. The primary outcome was the filling or closure of the fistula tract, including the external or internal openings. USPIO treatment allowed the closure and/or filling of all the treated fistulas from its application until POD 7 in comparison with the control fistulas (23%). The treatment with USPIO was safe, permanently closed the fistula along its entire length, including internal and external orifices, and paved new avenues for the treatment of perianal fistulizing Crohn’s disease.
Published: 2022
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8. I-FABP is decreased in COVID-19 patients, independently of the prognosis.

Author: Kevin Guedj, Mathieu Uzzan, Damien Soudan, Catherine Trichet, Antonino Nicoletti, Emmanuel Weiss, Hana Manceau, Alexandre Nuzzo, Olivier Corcos, Xavier Treton, and Katell Peoc'h
Subjects: Medicine, Science
Abstract: BackgroundSevere acute respiratory syndrome caused by the novel coronavirus (SARS-CoV-2) is frequently associated with gastrointestinal manifestations. Herein we evaluated the interest in measuring the intestinal fatty acid-binding protein (I-FABP), a biomarker of intestinal injury, in COVID-19 patients.MethodsSerum I-FABP was analyzed in 28 consecutive patients hospitalized for a PCR-confirmed COVID-19, in 24 hospitalized patients with non-COVID-19 pulmonary diseases, and 79 patients admitted to the emergency room for abdominal pain.ResultsI-FABP serum concentrations were significantly lower in patients with COVID-19, as compared to patients with non-COVID-19 pulmonary diseases [70.3 pg/mL (47-167.9) vs. 161.1 pg/mL (88.98-305.2), respectively, p = 0.008]. I-FABP concentrations in these two populations were significantly lower than in patients with abdominal pain without COVID-19 [344.8 pg/mL (268.9-579.6)]. I-FABP was neither associated with severity nor the duration of symptoms. I-FABP was correlated with polymorphonuclear cell counts.ConclusionsIn this pilot study, we observed a low I-FABP concentration in COVID-19 patients either with or without gastrointestinal symptoms, of which the pathophysiological mechanisms and clinical impact remain to be established. Further explorations on a larger cohort of patients will be needed to unravel the molecular mechanism of such observation, including the effects of malabsorption and/or abnormal lipid metabolism.
Published: 2021
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9. Control of anterior GRadient 2 (AGR2) dimerization links endoplasmic reticulum proteostasis to inflammation

Author: Marion Maurel, Joanna Obacz, Tony Avril, Yong‐Ping Ding, Olga Papadodima, Xavier Treton, Fanny Daniel, Eleftherios Pilalis, Johanna Hörberg, Wenyang Hou, Marie‐Claude Beauchamp, Julien Tourneur‐Marsille, Dominique Cazals‐Hatem, Lucia Sommerova, Afshin Samali, Jan Tavernier, Roman Hrstka, Aurélien Dupont, Delphine Fessart, Frédéric Delom, Martin E Fernandez‐Zapico, Gregor Jansen, Leif A Eriksson, David Y Thomas, Loydie Jerome‐Majewska, Ted Hupp, Aristotelis Chatziioannou, Eric Chevet, and Eric Ogier‐Denis
Subjects: AGR2, endoplasmic reticulum, inflammation, proteostasis, TMED2, Medicine (General), R5-920, Genetics, QH426-470
Abstract: Abstract Anterior gradient 2 (AGR2) is a dimeric protein disulfide isomerase family member involved in the regulation of protein quality control in the endoplasmic reticulum (ER). Mouse AGR2 deletion increases intestinal inflammation and promotes the development of inflammatory bowel disease (IBD). Although these biological effects are well established, the underlying molecular mechanisms of AGR2 function toward inflammation remain poorly defined. Here, using a protein–protein interaction screen to identify cellular regulators of AGR2 dimerization, we unveiled specific enhancers, including TMED2, and inhibitors of AGR2 dimerization, that control AGR2 functions. We demonstrate that modulation of AGR2 dimer formation, whether enhancing or inhibiting the process, yields pro‐inflammatory phenotypes, through either autophagy‐dependent processes or secretion of AGR2, respectively. We also demonstrate that in IBD and specifically in Crohn's disease, the levels of AGR2 dimerization modulators are selectively deregulated, and this correlates with severity of disease. Our study demonstrates that AGR2 dimers act as sensors of ER homeostasis which are disrupted upon ER stress and promote the secretion of AGR2 monomers. The latter might represent systemic alarm signals for pro‐inflammatory responses.
Published: 2019
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10. The Appendix Orchestrates T-Cell Mediated Immunosurveillance in Colitis-Associated Cancer

Author: Tourneur-Marsille J, Nathalie Guedj, Mathieu Uzzan, M. Collard, Yves Panis, Jean-Pierre Hugot, Dumay A, Jean-Noël Freund, Maryline Roy, Xavier Treton, Eric Ogier-Denis, M. Albuquerque, Service de Chirurgie colorectale [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Oncogenesis, Stress, Signaling (OSS), and Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, Lymphocyte, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology, Internal medicine, Laparotomy, medicine, Appendectomy, Ulcerative Colitis, Colitis, Hepatology, business.industry, Inflammatory Bowel Disease, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Appendicitis, Ulcerative colitis, Appendix, Immunosurveillance, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, business, CD8
Abstract: ObjectiveWhile appendectomy may reduce colorectal inflammation in patients with ulcerative colitis (UC), appendectomy has been suggested to be associated with an increased risk of colitis-associated cancer (CAC). The aim of this study was to explore the mechanism underlying the appendectomy-associated increased risk of CAC.DesignFive-week-old male BALB/c mice underwent appendectomy, appendicitis induction or sham laparotomy. They were then exposed to azoxymethane/dextran sodium sulfate (AOM/DSS) to induce CAC. Mice were sacrificed 12 weeks later, and colons were taken for pathological analysis and immunohistochemistry (CD3 and CD8 staining). Human colonic tumors from 21 UC patients who underwent surgical resection for CAC were immunophenotyped and stratified according to the appendectomy status.ResultsWhile appendectomy significantly reduced colitis severity and increased CAC number, appendicitis induction without appendectomy led to opposite results. Intra-tumor CD3+ and CD8+ T-cell densities were lower after appendectomy and higher after appendicitis induction compared to the sham laparotomy group. Blocking lymphocyte trafficking to the colon with the anti-α4β7 integrin antibody or a sphingosine-1-phosphate receptor agonist suppressed the inducing effect of the appendectomy on tumors’ number and on CD3+/CD8+ intra-tumoral density. CD8+ or CD3+ T cells isolated from inflammatory neo-appendix and intravenously injected into AOM/DSS-treated recipient mice increased CD3+/CD8+ T-cell tumor infiltration and decreased tumor number. In UC patients with a history of appendectomy, intra-tumor CD3+ and CD8+ T-cell densities were decreased compared to UC patients without history of appendectomy.ConclusionsIn UC, appendectomy could suppress a major site of T-cell priming resulting in a less efficient CAC immunosurveillance.Significance of this studyWhat is already known on this subject?The protective effect of preemptive appendectomy is currently investigated as a therapy for refractory ulcerative colitis (UC), with encouraging results.An increased risk of developing colitis-associated cancer (CAC) caused by this promising treatment has been identified.Since it is commonly accepted that CAC is related to colitis severity and extent, this finding is counterintuitive and the mechanisms of this paradoxical effect remain unknown.What are the new findings?In a mouse model of CAC, less extended colitis associated with an increased number of tumors was observed. Intra-tumor T-cell infiltration was significantly reduced after appendectomy. Blocking lymphocyte trafficking to the colon with current or experimental UC treatments mimicked the appendectomy-associated phenotype whereas neo-appendicitis or appendix-primed T-cell injection in recipient mice increased intra-tumor T-cell infiltration and strengthened protection against CAC.In UC patients with CAC, appendectomy was associated with a decreased intra-tumor T-cell infiltration.These findings suggest that, in UC, appendectomy could suppress a major site of T-cell priming in the colon, resulting in a reduced CAC immunosurveillance.How might it impact on clinical practice in the foreseeable future?This work emphasizes the fact that precautions will be necessary if appendectomy becomes an accepted therapeutic option for the treatment of refractory UC.Innovative cell-based therapies and immunotherapies, such as the administration of stimulated autologous appendicular T cells in patients with CAC are promising options.
Published: 2023

11. Intra‐abdominal abscesses in CD – When to treat with biologics?

Author: Manon Haas, Xavier Treton, Carmen Stefanescu, and Yoram Bouhnik
Subjects: Oncology, Gastroenterology
Abstract: Management of intra-abdominal abscesses complicating Crohn's disease (CD) is challenging. After initial drainage and antibiotherapy treatment, surgery with delayed intestinal resection is often recommended but new data suggests efficacy of biotherapies in this context. This review aims to summarize new data regarding efficacy and safety of anti-TNF in the management of intra-abdominal abscesses complicating CD. We performed a review of the literature on medical management of intra-abdominal abscesses complicating CD. After effective drainage of abscess, treatment with anti-TNF can allow resolving of abscess. In some patients and at a specific timing, the use of biotherapies could avoid delayed surgery and long-term abscess recurrence.
Published: 2022

12. Obesity in adult patients with inflammatory bowel disease: Clinical features and impact on disability. A cross-sectional survey from the GETAID

Author: Rose Al Bacha, Yoram Bouhnik, Melanie Serrero, Jerome Filippi, Xavier Roblin, Anne Bourrier, Guillaume Bouguen, Denis Franchimont, Guillaume Savoye, Anthony Buisson, Edouard Louis, Stephane Nancey, Vered Abitbol, Jean-Marie Reimund, Olivier DeWit, Lucine Vuitton, Nicolas Mathieu, Laurent Peyrin-Biroulet, Cyrielle Gilletta, Matthieu Allez, Stephanie Viennot, Catherine Le Berre, David Laharie, Maria Nachury, Aurelien Amiot, Sara Tadbiri, Charlotte Gagniere, Jenny Tannoury, Benjamin Pariente, Pauline Wils, Carmen Stefanescu, Xavier Treton, Carole Martins, Mathieu Uzzan, Xavier Hébuterne, Nadia Arab, Virginie Cluzeau, Emilie Del Tedesco, Laurent Beaugerie, Philippe Seksik, Cecilia Landmann, Julien Kirchgesner, Harry Sokol, Laurent Siproudhis, Marie DeWitte, Catherine Reenaers, Gilles Boschetti, Claire Gay, Pauline Danion, Bernard Flourié, Georgia Malamut, Benedicte Caron, Olivier DeWitt, Sandie Pestour, Thomas Chateau, Camille Zallot, Jean-Marc Gornet, Clotilde Baudry, Arnaud Bourreille, Caroline Trang-Poisson, Nina Dib, Hedi Brixi, Guillaume Cadiot, Medina Boualit, Claire Painchart, Laurianne Plastaras, Romain Altwegg, Lucile Boivineau, Mathurin Fumery, Ludovic Caillo, Pauline Riviere, Florian Poullenot, Benoit Coffin, Henri Duboc, Stephane Nahon, Noemie Tavernier, Marion Simon, Baya Coulibaly, Morgane Amil, Duveau Nicolas, Sherine Khater, Mehdi Kaassis, Felix Goutorbe, Driffa Moussata, Laurence Picon, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Nord [CHU - APHM], Immunité muqueuse et vaccination, 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)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Service de Gastro-entérologie et Hépatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), 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), CHU Pontchaillou [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), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), CHU Rouen, Normandie Université (NU), 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 Liège (CHU-Liège), Hospices Civils de Lyon (HCL), Hôpital Cochin [AP-HP], Voies de Signalisation du Développement et du Stress Cellulaire dans les Cancers Digestifs et Urologiques, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Service de Gastro-Entérologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Grenoble, Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hopital Saint-Louis [AP-HP] (AP-HP), CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Groupe d’Étude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID), and This study was supported by Abbvie.
Subjects: Crohn's disease, Disability, Ulcerative colitis, Hepatology, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Fatigue, Inflammatory bowel disease, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background: In recent years, an increasing prevalence of obesity in inflammatory bowel disease (IBD) has been observed. However, only a few studies have focused on the impact of overweight and obesity on IBD-related disability.Aims: To identify the factors associated with obese and overweight patients with IBD, including IBD-related disability.Patients and methods: In this cross-sectional study, we included 1704 consecutive patients with IBD in 42 centres affiliated with the Groupe d'Etude Therapeutique des Affections Inflammatoires du tube Digestif (GETAID) using a 4-page questionnaire. Factors associated with obesity and overweight were assessed using univariate and multivariate analyses (odds ratios (ORs) are provided with 95% confidence intervals).Results: The prevalence rates of overweight and obesity were 24.1% and 12.2%, respectively. Multivariable analyses were stratified by age, sex, type of IBD, clinical remission and age at diagnosis of IBD. Overweight was significantly associated with male sex (OR = 0.52, 95% CI [0.39-0.68], p < 0.001), age (OR = 1.02, 95% CI [1.01-1.03], p < 0.001) and body image subscore (OR = 1.15, 95% CI [1.10-1.20], p < 0.001) (Table 2). Obesity was significantly associated with age (OR = 1.03, 95% CI [1.02-1.04], p < 0.001), joint pain subscore (OR = 1.08, 95% CI [1.02-1.14], p < 0.001) and body image subscore (OR = 1.25, 95% CI [1.19-1.32], p < 0.001) (Table 3).Conclusion: The increasing prevalence of overweight and obesity in patients with IBD is associated with age and poorer body image. A holistic approach to IBD patient care should be encouraged to improve IBD-related disability and to prevent rheumatological and cardiovascular complications.
Published: 2023

13. Inflammatory bowel diseases’s treatment in 2022

Author: Xavier Treton
Published: 2022

14. Adalimumab in biologic-naïve patients with Crohn’s disease after resolution of an intra-abdominal abscess: a prospective study from the GETAID

Author: Yoram Bouhnik, Guillaume Pineton de Chambrun, Jérôme Lambert, Maria Nachury, Philippe Seksik, Romain Altwegg, Lucine Vuitton, Carmen Stefanescu, Stéphane Nancey, Alexandre Aubourg, Mélanie Serrero, Jérôme Filippi, Kristell Desseaux, Stéphanie Viennot, Vered Abitbol, Madina Boualit, Arnaud Bourreille, Cyrielle Giletta, Anthony Buisson, Xavier Roblin, Nina Dib, Georgia Malamut, Aurélien Amiot, Mathurin Fumery, Edouard Louis, Yasmine Elgharabawy, Laurent Peyrin-Biroulet, Jacques Moreau, Xavier Treton, Charlotte Mailhat, Justine Pollet, Carole Martins, Guillaume Savoye, Noémie Tavernier, Jean-Yves Mary, Magali Zappa, Claire Painchart, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Hopital Saint-Louis [AP-HP] (AP-HP), 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), 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), Service de Gastro-Entérologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Nord [CHU - APHM], Centre Hospitalier Universitaire de Nice (CHU Nice), Université Paris Diderot - Paris 7 (UPD7), Université Sorbonne Paris Cité (USPC), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Gastro-entérologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Clermont-Ferrand, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service de Gastro-entérologie et Hépatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], 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: Crohn’s disease, surgery, Hepatology, adalimumab, Gastroenterology, abscess, anti-TNF, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background & aims: The management of intra-abdominal abscesses complicating Crohn's disease (CD) is challenging and surgery with delayed intestinal resection is often recommended. The aims of this study were to estimate the success rate of adalimumab (ADA) in CD patients with an intra-abdominal abscess resolved without surgery, and to identify predictive factors for success.Methods: A multicenter, prospective study was conducted in biologic-naïve CD patients with resolved intra-abdominal abscess treated with ADA with a two-year follow-up. The primary endpoint was ADA failure at W24 defined as a need for steroids after W12, intestinal resection, abscess recurrence, and clinical relapse. Secondary post-hoc endpoint was the long-term success defined as the survival without abscess relapse or intestinal resection at W104. The factors associated with ADA failure at W24 and W104 were identified using a logistic and a cox regression, respectively.Results: From April 2013 to December 2017, 190 patients from 27 GETAID centers were screened, and 117 were included in the analysis. Fifty-eight (50%) patients were male and the median age at baseline was 28 years. At W24, 87 (74%, 95%CI: 65.5-82.0, n=117) patients achieved ADA success. Among the 30 patients with ADA failure, 15 underwent surgery. At W104, the survival rate without abscess recurrence or surgery was 72·9% (95%CI: 62.1-79.8, n=109). Abscess drainage was significantly associated with ADA failure at W24 (OR=4.18; 95%CI: 1.06-16.5; p=0.043). Disease duration (HR=1.32, 95%CI: 1.09-1.59, p=0.008), abscess drainage (HR=5.59, 95%CI: 2.21-14.15, p=0.001), and inflammatory changes in mesenteric fat (HR=0.4, 95%CI: 0.17-0.94, p=0.046) were significantly associated with ADA failure at W104.Conclusion: Provided that the abscess was carefully managed before initiating medical treatment, this study showed the high efficacy of ADA in the short and long term in biologic-naïve patients with CD complicated by an intra-abdominal abscess.
Published: 2023

15. Effectiveness and safety of ustekinumab maintenance therapy in 103 patients with ulcerative colitis: a GETAID cohort study

Author: Mathurin Fumery, Jérôme Filippi, Vered Abitbol, Amélie Biron, David Laharie, Melanie Serrero, Romain Altwegg, Yoram Bouhnik, Laurent Peyrin‐Biroulet, Cyrielle Gilletta, Xavier Roblin, Guillaume Pineton de Chambrun, Lucine Vuitton, Anne Bourrier, Stephane Nancey, Jean‐Marc Gornet, Stephane Nahon, Guillaume Bouguen, Stephanie Viennot, Maria Nachury, Aurelien Amiot, Franck Brazier, Clara Yzet, Xavier Hebuterne, Guillaume Cadiot, Hedia Brixi, Pauline Rivière, Florian Poullenot, Xavier Treton, Carmen Stefanescu, Camille Zallot, Laurent Beaugerie, Philippe Seksik, Harry Sokol, Julien Kirchgesner, Gilles Boschetti, Bernard Flourié, Claire Gay, Pauline Danion, Chloe Venturin, Matthieu Allez, Clotilde Baudry, Benjamin Pariente, Pauline Wils, Charlotte Gagnière, Jenny Tannoury, CHU Amiens-Picardie, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Bordeaux [Bordeaux], CHU Marseille, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Nancy (CHU Nancy), CHU Toulouse [Toulouse], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Lille, CHI Créteil, GETAID, Université de Montpellier (UM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and 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)
Subjects: Adult, Male, medicine.medical_specialty, Pancolitis, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Vedolizumab, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, Internal medicine, Ustekinumab, Humans, Medicine, Pharmacology (medical), Adverse effect, Colectomy, Hepatology, business.industry, Remission Induction, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Middle Aged, medicine.disease, Ulcerative colitis, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Colitis, Ulcerative, 030211 gastroenterology & hepatology, medicine.symptom, business, medicine.drug, Cohort study
Abstract: International audience; Background Phase III trials have demonstrated the efficacy and safety of ustekinumab in ulcerative colitis (UC), but few real-life long-term data are currently available. Aims To assess the real-world effectiveness and safety of ustekinumab in patients with UC. Methods From January to September 2019, all consecutive patients with active UC treated with ustekinumab in a GETAID centre were included. Patients were evaluated at week 52. Remission was defined as a partial Mayo Clinic score
Published: 2021

16. Prevalence of anti-TNF contraindications in Crohn’s disease: A cross-sectional survey from the GETAID

Author: Aurelien Amiot, Philippe Seksik, Jean-Marie Reimund, Maria Nachury, Romain Altwegg, Arnaud Bourreille, Stephanie Viennot, Mathurin Fumery, Xavier Roblin, Melanie Serrero, Matthieu Allez, Claire Painchart, Elise Chanteloup, Lucine Vuitton, Ginette Fotsing, Anthony Buisson, Baya Coulibaly, Stephane Nancey, Cyrielle Gilletta, Laurianne Plastaras, Vered Abitbol, Lucas Guillo, Marion Simon, Stephane Nahon, David Laharie, Laurent Peyrin-Biroulet, Guillaume Bouguen, Charlotte Gagniere, Pauline Wils, Yoram Bouhnik, Carmen Stefanescu, Xavier Treton, Carole Martins, Mathieu Uzzan, Emilie Del Tedesco, Laurent Beaugerie, Anne Bourrier, Cecilia Landmann, Julien Kirchgesner, Harry Sokol, Gilles Boschetti, Claire Gay, Pauline Danion, Bernard Flourié, Georgia Malamut, Benedicte Caron, Camille Zallot, Jean-Marc Gornet, Clotilde Baudry, Caroline Trang-Poisson, Medina Boualit, Lucile Boivineau, Pauline Riviere, Florian Poullenot, Benoit Coffin, Henri Duboc, 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 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), Voies de Signalisation du Développement et du Stress Cellulaire dans les Cancers Digestifs et Urologiques, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), University Hospital of Montpellier, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), 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, Groupe d’Étude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Aix Marseille Université (AMU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier [Valenciennes, Nord], Hôpital Saint-Joseph [Marseille], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Clermont-Ferrand, Centre Hospitalier Henri Duffaut (Avignon), Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CH Colmar, Hôpital Cochin [AP-HP], Institut Mutualiste de Montsouris (IMM), Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, CHU Bordeaux [Bordeaux], 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), 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], This study was supported by an institutional grant by Takeda, CRHU Nancy, 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 Saint-Etienne, and CHU Toulouse [Toulouse]
Subjects: Crohn’s disease, Hepatology, Contraindications, [SDV]Life Sciences [q-bio], Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Inflammatory bowel disease, Anti-TNF, Cross-Sectional Studies, Treatment Outcome, Crohn Disease, Prevalence, Humans, Tumor Necrosis Factor Inhibitors, Ustekinumab, Contraindication
Abstract: International audience; BACKGROUND: The exact rate of contraindications to anti-TNF therapy and physician perspectives on treatment choices facing to anti-TNF contraindication, are poorly reported. METHODS: A two-week cross-sectional study was conducted in 31 centres. Physicians completed a questionnaire for a total of 1,314 consecutive outpatients with Crohn’s disease, assessing each patient’s potential contraindications to anti-TNF therapy, the choice of alternative therapy to anti-TNFs, and their preference in an unrestricted reimbursement setting. RESULTS: Among the 1,293 responses to the first item, 148 (11.5%) reported 32 absolute contraindications (2.5%) and 116 relative contraindications (9.0%) to anti-TNF therapy. When asked about their preference of alternative therapies in those cases with contraindications to anti-TNF, physicians chose ustekinumab and vedolizumab, 75.6% and 23.9%, respectively. In multivariable analysis, the choice of vedolizumab was the preferred choice for patients aged > 60 years with the L2 phenotype and the absence of perianal lesions. In a hypothetical setting of unrestricted reimbursement, anti-TNFs remained physicians’ preferred first-line biological therapy choice for 78.2%. CONCLUSION: Anti-TNF contraindications occurred in up to 11.5% of patients with Crohn’s disease. Physicians’ choices for alternative therapy to anti-TNF relied on ustekinumab in 75.6% and vedolizumab in 23.9% of these cases. This choice was driven mainly by phenotypical criteria and age.
Published: 2022

17. Impact of Crohn's disease on obstetrical management

Author: Laure Payet, Violaine Peyronnet, Camille Thouny, Benoit Coffin, Pierre-François Ceccaldi, Imane Ben M'Barek, Xavier Treton, Irène Letendre, and Laurent Mandelbrot
Subjects: Reproductive Medicine, Crohn Disease, Pregnancy, Cesarean Section, Risk Factors, Obstetrics and Gynecology, Humans, Female, Delivery, Obstetric, Lacerations, Retrospective Studies
Abstract: Patients with Crohn's disease (CD) may have perineal lesions or a history of anorectal surgery that raise concerns about complications during delivery resulting in a discussion of cesarean section. Our objective was to study the impact of CD on the mode of delivery.We conducted a retrospective study between 2005 and 2019 of the pregnancy outcomes of patients with CD. The primary endpoint was the performance of a cesarean section for a reason related to CD.Among 76 consecutive pregnancies, 19 patients underwent CD-related cesarean section (25%). The main element associated with scheduling a cesarean section was the existence of perineal involvement in 94.7% of cases, compared to 12.3% in the rest of the CD population (p0.05). The perineal lesions most often involved were fistulas (47.4% versus 1.7%; p = 0.042). There was a history of perineal surgery in 78.9% of cases in the cesarean group vs 10,5% (p0.05) and a history of obstetric anal sphincter injury (OASI) in 10.5% of cases vs. 0 (p = 0.047). In women who gave birth vaginally, there were 17.9% episiotomy and one case of OASI (2.6%).The factors that influenced the choice of delivery route were perineal damage, history of perineal surgery and history of OASI.
Published: 2022

18. Long‐term efficacy of fibrin glue injection for perianal fistulas in patients with Crohn's disease

Author: Xavier Treton, Helene Corte, Jean-Marc Gornet, Jérôme Lambert, Nicolas Munoz-Bongrand, Mathias Vidon, Yves Panis, Jean-David Zeitoun, Philippe Seksik, Laurent Abramowitz, Matthieu Allez, and Léon Maggiori
Subjects: Adult, Anal fistula, medicine.medical_specialty, Combination therapy, Fistula, Population, Fibrin Tissue Adhesive, law.invention, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Randomized controlled trial, law, Humans, Rectal Fistula, Medicine, Cumulative incidence, education, Fibrin glue, Retrospective Studies, education.field_of_study, Crohn's disease, business.industry, Gastroenterology, medicine.disease, Surgery, Treatment Outcome, 030220 oncology & carcinogenesis, Tissue Adhesives, 030211 gastroenterology & hepatology, business
Abstract: Aim The treatment of perianal fistulas in Crohn's disease remains challenging. Fibrin glue injection has previously shown short-term efficacy in a randomized controlled trial. No long-term data are available to assess the benefit of this treatment. Methods This retrospective multicentre study included all patients with drained fistulas treated by at least one fibrin glue injection between January 2004 and June 2015 in three tertiary French centres. The primary end-point was the rate of complete clinical remission at 1 year after injection defined by the closure of all fistula tracts with no need for iterative anal surgery or for optimization of immunosuppressants and/or biologics. Results In all, 119 patients (median age 33 years, complex fistulas 65%, median previous anal surgery two, median Harvey Bradshaw score 3, immunosuppressants exposure 50%, anti-tumor necrosis factor exposure 60% with median time of administration of 1.1 year) were analysed with a median follow-up of 18.3 months. The complete clinical remission rate at 1 year was 45.4%. The primary end-point was achieved in 63% of the cases in the combination therapy group and 37% in other patients. The only predictor of complete clinical remission at 1 year was combination therapy at the time of injection (P = 0.01). The rate of early reintervention after glue injection was 2.5%. The cumulative incidence of iterative anal surgery and ostomy in the whole population was 54% and 5.6% respectively at 5 years. Conclusion An adjunct of fibrin glue to conventional medical therapy may be an effective and safe treatment for perianal fistulas in patients with Crohn's disease.
Published: 2020

19. Management of immune checkpoint inhibitor in patients with cancer and pre-existing inflammatory bowel disease: Recommendations from the GETAID

Author: Aurelien Amiot, David Laharie, Georgia Malamut, Melanie Serrero, Florian Poullenot, Laurent Peyrin-Biroulet, Arnaud Bourreille, Lucine Vuitton, Guillaume Bouguen, Vered Abitbol, Amelie Biron, Anne Bourrier, Ludovic Caillo, Mathurin Fumery, Cyrielle Gilletta, Laurianne Plastaras, Marion Simon, Stephanie Viennot, Philippe Seksik, Alain Attar, Anthony Buisson, Benedicte Caron, Maeva Charkaoui, Jean-Marc Gornet, Lucas Guillo, Catherine Le Berre, Edouard Louis, Nicolas Mathieu, Maria Nachury, Stephane Nancey, Stephane Paul, Catherine Reenaers, Xavier Treton, Mathieu Uzzan, and Pauline Wils
Subjects: Diarrhea, Hepatology, Recurrence, Neoplasms, Gastroenterology, Humans, Colitis, Inflammatory Bowel Diseases, Immune Checkpoint Inhibitors, Retrospective Studies
Abstract: There is no consensus on the management of immune checkpoint inhibitor (ICI) for treating cancer in patients with pre-existing inflammatory bowel disease (IBD). The Groupe d'Étude Thérapeutique des Affections Inflammatoires du tube Digestif (GETAID) aimed to provide recommendations on this topic.A dedicated working group performed a comprehensive expert-based review of the literature, generated clinical key question and shaped recommendations that were further voted for approval by the educational and scientific committees of the GETAID. Using consensus methods, treatment modalities were defined by vote.Majority of patients with IBD in clinical remission can be treated with ICI after cancer diagnosis. The rate of relapse or immune-related diarrhoea or colitis upon ICI treatment is up to 39.8% and is maximal with ICI combination therapy compared to monotherapies. When starting ICI in a patient with IBD, it is recommended to assess disease activity and pursue ongoing maintenance therapy. In case of relapse or immune-related diarrhoea or colitis upon ICI treatment, treatment depends on grading of diarrhoea or colitis and may include corticosteroid therapy, infliximab and/or vedolizumab.In the present publication, we provided recommendations, which may assist gastroenterologists, haematologists, and oncologists for a better management of patients with pre-existing IBD before and during cancer treatment with ICI.
Published: 2022

20. Role of adherent and invasive Escherichia coli in Crohn’s disease: lessons from the postoperative recurrence model

Author: Anthony Buisson, Harry Sokol, Nassim Hammoudi, Stéphane nancey, Xavier Treton, Maria Nachury, Mathurin Fumery, Xavier Hébuterne, Michael Rodrigues, Jean-Pierre Hugot, Gilles Boschetti, Carmen Stefanescu, Pauline Wils, Philippe Seksik, Lionel Le Bourhis, Madeleine Bezault, Pierre Sauvanet, Bruno Pereira, Matthieu Allez, Nicolas Barnich, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Infection Inflammation et Interaction Hôtes Pathogènes [CHU Clermont-Ferrand] (3IHP ), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), 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), Paris Center for Microbiome Medicine (FHU PaCeMM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), 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), 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), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Servcie Hépato-gastroentérolgie et Nutrition clinique [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), 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), Remind Study Group, Service de Chirurgie Digestive et Hépatobiliaire [CHU Clermont-Ferrand], Unité de Biostatistiques [CHU Clermont-Ferrand], MSD France, Association François Aupetit, Helmsley Charitable Trust, Ministère de la Recherche et de la Technologie, Inserm (UMR 1071), University of Clermont Auvergne, Inserm {National Programme 'Microbiote'], INRAE (USC-2018), and ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016)
Subjects: Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Abstract: ObjectiveWe used the postoperative recurrence model to better understand the role of adherent and invasiveEscherichia coli(AIEC) bacteria in Crohn’s disease (CD), taking advantage of a well-characterised postoperative cohort.DesignFrom a prospective, multicentre cohort of operated patients with CD, AIEC identification was performed within the surgical specimen (M0) (N=181 patients) and the neoterminal ileum (n=119 patients/181) during colonoscopy performed 6 months after surgery (M6). Endoscopic postoperative recurrence was graded using Rutgeerts’ index. The mucosa-associated microbiota was analysed by 16S sequencing at M0 and M6. Relative risks or ORs were adjusted on potential confounders.ResultsAIEC prevalence was twofold higher within the neoterminal ileum at M6 (30.3%) than within the surgical specimen (14.9%) (pRuminococcus gnavus.ConclusionBased on the postoperative recurrence model, our data support the idea that AIEC are involved in the early steps of ileal CD.Trial registration numberNCT03458195.
Published: 2022

21. Real‐world comparison of effectiveness between tofacitinib and vedolizumab in patients with ulcerative colitis exposed to at least one anti‐ TNF agent

Author: Anthony Buisson, Maria Nachury, Thomas Guilmoteau, Romain Altwegg, Xavier Treton, Mathurin Fumery, Melanie Serrero, Eloïse Leclerc, Ludovic Caillo, Bruno Pereira, Aurélien Amiot, Guillaume Bouguen, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Infection Inflammation et Interaction Hôtes Pathogènes [CHU Clermont-Ferrand] (3IHP ), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), 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 Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), 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, Hôpital Nord [CHU - APHM], Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Unité de Biostatistiques [CHU Clermont-Ferrand], Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Pfilzer, 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 Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Hepatology, Gastroenterology, Pharmacology (medical), [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background: Data comparing tofacitinib and vedolizumab in ulcerative colitis (UC) are lacking.Aims: To compare the effectiveness of tofacitinib and vedolizumab in patients with UC who had prior exposure to anti-TNF therapy METHODS: In this multicentre study, we included consecutive patients with UC ≥18 years old with partial Mayo score >2 and prior anti-TNF exposure, who started tofacitinib or vedolizumab between January 2019 and June 2021. Comparisons were performed using propensity score analyses (inverse probability of treatment weighting).Results: Overall, 126 and 178 patients received tofacitinib and vedolizumab, respectively. Intensified induction (vedolizumab infusion at week 10 or tofacitinib 10 mg b.d until week 16) was performed in 28.5% and 41.5% of patients, respectively. After propensity-score analysis, corticosteroid-free clinical remission (partial Mayo score ≤2) was achieved at week 16 in 45.1% and 40.2% of patients receiving tofacitinib and vedolizumab, respectively (aOR = 0.82 [0.35-1.91], p = 0.64). Endoscopic improvement (corticosteroid-free clinical remission and endoscopic Mayo score ≤1) (aOR = 0.23[0.08-0.65], p = 0.0032) and histological healing (endoscopic improvement + Nancy histological index ≤1) (13.4% vs 3.2%, aOR = 0.21[0.05-0.91], p = 0.023) were higher at week 16 in patients treated with tofacitinib. No factor was predictive of tofacitinib effectiveness. At least one primary failure to a biologic (OR = 0.46[0.22-0.99], p = 0.049), partial Mayo score >6 (OR = 0.39[0.17-0.90], p = 0.029) and CRP level > 30 mg/L at baseline (OR = 0.08[0.01-0.85], p = 0.036) were associated with vedolizumab failure.Conclusion: Tofacitinib and vedolizumab are effective in UC after failure of anti-TNF agents. However, tofacitinib seems more effective, especially in severe disease and primary failure to biologics.
Published: 2022

22. The Heterochromatin protein 1 is a master regulator in RNA splicing precision deficient in ulcerative colitis

Author: Jorge Mata-Garrido, Yao Xiang, Yunhua Chang-Marchand, Caroline Reisacher, Elisabeth Ageron-ardila, Chiara Guerrera, Inigo Casafont, Aurelia Bruneau, Claire Cherbuy, Xavier Treton, Anne Dumay, Eric Ogier-Denis, Eric Batsche, Mickael Costallat, Gwladys Revêchon, Maria Eriksson, Christian Muchardt, Laurence Arbibe, Batsche, Eric, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Universidad de Cantabria [Santander], Unité de recherche d'Écologie et Physiologie du Système Digestif (UEPSD), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Karolinska Institutet [Stockholm]
Subjects: Heterochromatin protein, integumentary system, [SDV]Life Sciences [q-bio], master regulator, RNA, Biology, Progerin, Intestinal epithelium, Gut Epithelium, Cell biology, LMNA, [SDV] Life Sciences [q-bio], Ageing, Ectopic expression, Epigenetics
Abstract: Defects in RNA splicing have been linked to numerous human disorders, but remain poorly explored in inflammatory bowel disease (IBD). Here, we report that, in the gut epithelium of patients with ulcerative colitis (UC), the expression of the chromatin and alternative splicing regulator HP1γ is strongly reduced. Accordingly, inactivation of the HP1γ gene in the mouse gut triggered several IBD-like traits, including inflammation and dysbiosis. In parallel, we discovered that its loss of function broadly increased splicing noise, reducing requirement for canonical splicing consensus sequences, and favoring the usage of cryptic splice sites at numerous genes with key functions in gut biology. This notably resulted in the production of progerin, a noncanonical toxic splice variant of prelamin A mRNA, responsible for the Hutchinson Gilford Progeria Syndrome (HGPS) of premature aging. Likewise, production of progerin transcript was found to be a signature of colonic cells from UC patients. Thus, our study identifies HP1γ as a regulator of RNA metabolism in vivo, providing a unique mechanism linking anti-inflammation and accuracy of RNA splicing in the gut epithelium. HP1 defect may confer a general disturbance in RNA splicing precision to scrutinize in IBD and more generally in accelerating aging diseases.
Published: 2022

23. Patients’ real-world experience with inflammatory bowel disease: A cross-sectional survey in tertiary care centres from the GETAID group

Author: Maria Nachury, Yoram Bouhnik, Melanie Serrero, Jerome Filippi, Xavier Roblin, Julien Kirchgesner, Guillaume Bouguen, Denis Franchimont, Guillaume Savoye, Anthony Buisson, Edouard Louis, Stephane Nancey, Vered Abitbol, Jean-Marie Reimund, Olivier DeWit, Lucine Vuitton, Nicolas Matthieu, Laurent Peyrin-Biroulet, Cyrielle Gilletta, Sara Tadbiri, Matthieu Allez, Stephanie Viennot, Arnaud Bourreille, David Laharie, Aurelien Amiot, Charlotte Gagniere, Jenny Tannoury, Benjamin Pariente, Pauline Wils, Carmen Stefanescu, Xavier Treton, Xavier Hébuterne, Nadia Arab, Virginie Cluzeau, Emilie Del Tedesco, Laurent Beaugerie, Philippe Seksik, Anne Bourrier, Cecilia Landmann, Harry Sokol, Laurent Siproudhis, Marie DeWitte, Catherine Reenaers, Gilles Boschetti, Claire Gay, Pauline Danion, Bernard Flourié, Georgia Malamut, Benedicte Caron, Olivier DeWitt, Nicolas Mathieu, Sandie Pestour, Camille Zallot, Jean-Marc Gornet, Clotilde Baudry, Caroline Trang-Poisson, Nina Dib, Hedi Brixi, Guillaume Cadiot, Medina Boualit, Claire Painchart, Laurianne Plastaras, Romain Altwegg, Lucile Boivineau, Mathurin Fumery, Ludovic Caillo, Pauline Riviere, Florian Poullenot, Benoit Coffin, Henri Duboc, Stephane Nahon, Noemie Tavernier, Marion Simon, Baya Coulibaly, Morgane Amil, Duveau Nicolas, Sherine Khater, Mehdi Kaassis, Felix Goutorbe, Driffa Moussata, Laurence Picon, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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], CIC - Biotherapie - Marseille, Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Pasteur [Nice] (CHU), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), 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], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), CHU Rouen, Normandie Université (NU), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Université Clermont Auvergne (UCA), Centre Hospitalier Universitaire de Liège (CHU-Liège), Service d'Hépatologie et de Gastroentérologie [Lyon], 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), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de Hautepierre [Strasbourg], Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Cliniques Universitaires Saint-Luc [Bruxelles], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire [Grenoble] (CHU), 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 Toulouse (CHU Toulouse), Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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), Hopital Saint-Louis [AP-HP] (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier universitaire de Nantes (CHU Nantes), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque - CHU de Bordeaux (Centre médico chirurgical Magellan), AbbVie, GETAID-patient experience study group: Aurelien Amiot , Sara Tadbiri , Charlotte Gagniere , Jenny Tannoury , Maria Nachury , Benjamin Pariente , Pauline Wils , Yoram Bouhnik , Carmen Stefanescu , Xavier Treton , Melanie Serrero , Jerome Filippi , Xavier Hébuterne , Nadia Arab , Virginie Cluzeau , Xavier Roblin , Emilie Del Tedesco , Laurent Beaugerie , Philippe Seksik , Anne Bourrier , Cecilia Landmann , Julien Kirchgesner , Harry Sokol , Guillaume Bouguen , Laurent Siproudhis , Marie DeWitte , Denis Franchimont , Guillaume Savoye , Anthony Buisson , Edouard Louis , Catherine Reenaers , Stephane Nancey , Gilles Boschetti , Claire Gay , Pauline Danion , Bernard Flourié , Vered Abitbol , Georgia Malamut , Jean-Marie Reimund , Benedicte Caron , Olivier DeWitt , Lucine Vuitton , Nicolas Mathieu , Sandie Pestour , Laurent Peyrin-Biroulet , Camille Zallot , Cyrielle Gilletta , Matthieu Allez , Jean-Marc Gornet , Clotilde Baudry , Stephanie Viennot , Arnaud Bourreille , Caroline Trang-Poisson , Nina Dib , Hedi Brixi , Guillaume Cadiot , Medina Boualit , Claire Painchart , Laurianne Plastaras , Romain Altwegg , Lucile Boivineau , Mathurin Fumery , Ludovic Caillo , David Laharie , Pauline Riviere , Florian Poullenot , Benoit Coffin , Henri Duboc , Stephane Nahon , Noemie Tavernier , Marion Simon , Baya Coulibaly , Morgane Amil , Duveau Nicolas , Sherine Khater , Mehdi Kaassis , Felix Goutorbe , Driffa Moussata , Laurence Picon, CHU Saint-Etienne, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Autophagie infection et immunité - Autophagy Infection Immunity (APY), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Voies de Signalisation du Développement et du Stress Cellulaire dans les Cancers Digestifs et Urologiques, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Catholique de Louvain = Catholic University of Louvain (UCL), CHU Toulouse [Toulouse], CIC - Biotherapie - CHU Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - (SLuc) Service de gastro-entérologie, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, 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)-Centre National de la Recherche Scientifique (CNRS), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), 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)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Crohn’s disease, medicine.medical_specialty, Health Knowledge, Attitudes, Practice, Cross-sectional study, [SDV]Life Sciences [q-bio], Disease, Patients experience, Inflammatory bowel disease, Tertiary care, digestive system, Tertiary Care Centers, 03 medical and health sciences, 0302 clinical medicine, Belgium, Physicians, Outpatients, medicine, Quantitative assessment, Humans, Adverse effect, Crohn's disease, Physician-Patient Relations, Hepatology, business.industry, Gastroenterology, Middle Aged, Patient Acceptance of Health Care, medicine.disease, Inflammatory Bowel Diseases, Ulcerative colitis, digestive system diseases, 3. Good health, Cross-Sectional Studies, 030220 oncology & carcinogenesis, Family medicine, 030211 gastroenterology & hepatology, Female, France, Self Report, business
Abstract: International audience; BACKGROUND: Patients’ experience with healthcare professionals could influence their clinical outcomes. AIMS: To assess inflammatory bowel disease (IBD) patients’ experience with their disease, their treatment and their relationship with their physician. METHODS: A one-week cross-sectional study was conducted in 42 IBD centres. 2011 consecutive outpatients with IBD completed an anonymous self-report questionnaire assessing their experience with and knowledge of IBD. RESULTS: A quantitative assessment of the doctor-patient relationship revealed that patients’ knowledge of IBD and IBD treatment ranged from 7.4 to 8.3 out of 10. In addition to IBD physicians, other sources of information about IBD and current treatment mainly included the internet (80% and 63%, respectively) and general practitioners (61% and 54%). Knowledge about education programmes (28%) was poor, resulting in a lack of willingness to further use these resources (25%). Concerns about IBD treatment were raised in 76% of patients, mostly related to the fear of adverse events (47%) and a lack of efficacy (33%). The need of alternative healthcare professionals was reported by 89% of the sample. CONCLUSION: In a large cohort of patients, we highlighted gaps in the management of patients with IBD regarding the need for higher-quality information and the implementation of alternative healthcare professionals.
Published: 2021

24. Effectiveness and Safety of Ustekinumab Intensification at 90 mg Every 4 Weeks in Crohn’s Disease: A Multicentre Study

Author: Lieven Pouillon, Guillaume Bouguen, Bernard Flourié, Mathurin Fumery, Stephanie Viennot, Laurent Siproudhis, Franck Brazier, Jérôme Filippi, Pauline Veyrard, Florian Poullenot, Anthony Buisson, Lucile Boivineau, Xavier Treton, Momar Diouf, David Laharie, Cyrielle Gilletta, Stéphane Nancey, Romain Altwegg, Xavier Roblin, Anne Bozon, and Laurent Peyrin-Biroulet
Subjects: medicine.medical_specialty, Crohn's disease, medicine.diagnostic_test, business.industry, Gastroenterology, Colonoscopy, General Medicine, medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, Ustekinumab, medicine, 030211 gastroenterology & hepatology, 030212 general & internal medicine, Every Four Weeks, Calprotectin, Adverse effect, business, medicine.drug, Cohort study
Abstract: Background The approved maintenance regimens for ustekinumab in Crohn’s disease [CD] are 90 mg every 8 or 12 weeks. Some patients will respond partially to ustekinumab or will experience a secondary loss of response. It remains poorly known if these patients may benefit from shortening the interval between injections. Methods All patients with active CD, as defined by Harvey–Bradshaw score ≥ 4 and one objective sign of inflammation [C-reactive protein > 5 mg/L and/or faecal calprotectin > 250 µg/g and/or radiological and/or endoscopic evidence of disease activity] who required ustekinumab dose escalation to 90 mg every 4 weeks for loss of response or incomplete response to ustekinumab 90 mg every 8 weeks were included in this retrospective multicentre cohort study. Results One hundred patients, with a median age of 35 years [interquartile range, 28–49] and median disease duration of 12 [7–20] years were included. Dose intensification was performed after a median of 5.0 [2.8–9.0] months of ustekinumab treatment and was associated with corticosteroids and immunosuppressants in respectively 29% and 27% of cases. Short-term clinical response and clinical remission were observed in respectively 61% and 31% after a median of 2.4 [1.3–3.0] months. After a median follow-up of 8.2 [5.6–12.4] months, 61% of patients were still treated with ustekinumab, and 26% were in steroid-free clinical remission. Among the 39 patients with colonoscopy during follow-up, 14 achieved endoscopic remission [no ulcers]. At the end of follow-up, 27% of patients were hospitalized, and 19% underwent intestinal resection surgery. Adverse events were reported in 12% of patients, including five serious adverse events. Conclusion In this multicentre study, two-thirds of patients recaptured response following treatment intensification with ustekinumab 90 mg every 4 weeks.
Published: 2020

25. Small‐Bowel Adaptation: A Case of Morphological Changes Induced by Teduglutide in Short‐Bowel Syndrome With Intestinal Failure

Author: Emilie Ferrandi, Thomas Mouillot, Francisca Joly, Nathalie Kapel, Dominique Cazals-Hatem, Xavier Treton, and V. Boehm
Subjects: Adult, Short Bowel Syndrome, medicine.medical_specialty, 030309 nutrition & dietetics, medicine.medical_treatment, Medicine (miscellaneous), Inflammatory bowel disease, Teduglutide, Gastroenterology, Intestinal absorption, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Gastrointestinal Agents, Capsule endoscopy, law, Internal medicine, Intestine, Small, Glucagon-Like Peptide 2, Humans, Medicine, 0303 health sciences, Nutrition and Dietetics, business.industry, Short bowel syndrome, medicine.disease, Small intestine, medicine.anatomical_structure, Parenteral nutrition, chemistry, Jejunostomy, Female, 030211 gastroenterology & hepatology, Peptides, business
Abstract: Teduglutide (TED) reduces the need for parenteral support (PS) in patients with short-bowel syndrome with intestinal failure (SBS-IF). It is a glucagon-like peptide-2 analog that improves absorption, induces the expansion of the absorptive epithelium in the small intestine, and may be used in patients with SBS-IF after a 6- to 12-month adaptation period, if PS is always necessary. We described the functional and morphological effect of TED in a 40-year-old female patient with SBS-IF due to Crohn's disease who underwent terminal jejunostomy after 12 months of drug exposition. Marked hypertrophy of the villi was detected by endoscopic capsule and confirmed by histological measurements. This is the first publication demonstrating an increase in intestinal absorption in an SBS-IF patient treated with TED because of a morphological adaptation of the small bowel, with hyperplasia confirmed by capsule endoscopy and histology. The capsule endoscopy, a noninvasive exploration of the gut, could be evaluated to monitor the real efficacy of treatments with growth factors in SBS patients.
Published: 2020

26. Prognosis of Lymphoma in Patients With Known Inflammatory Bowel Disease: A French Multicentre Cohort Study

Author: Vered Abitbol, Aurelien Amiot, Caroline Besson, Xavier Treton, Laurent Beaugerie, Catherine Thieblemont, Paul Coppo, Anouk Walter-Petrich, Thomas Aparicio, Georgia Malamut, Julien Kirchgesner, Lionel Galicier, Dominique Cazals-Hatem, Bénédicte Deau-Fischer, Matthieu Allez, Jean Marc Gornet, T. Severyns, Jérôme Lambert, Service d'hépato-gastro-entérologie [Hôpital Saint-Louis, APHP], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Institut Universitaire d'Hématologie [Hôpital Saint-Louis - APHP], Hopital Saint-Louis [AP-HP] (AP-HP), CHU Henri Mondor AP-HP/UPEC, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Hôpital Beaujon, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Unité de neurophysiologie [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), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
Subjects: Male, medicine.medical_specialty, Lymphoma, [SDV]Life Sciences [q-bio], medicine.medical_treatment, IBD, Population, Antineoplastic Agents, Lymphoma, T-Cell, Inflammatory bowel disease, Gastroenterology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Interquartile range, hemic and lymphatic diseases, Internal medicine, medicine, Humans, B-cell lymphoma, education, Digestive System Surgical Procedures, Neoplasm Staging, Biological Products, education.field_of_study, Chemotherapy, business.industry, Retrospective cohort study, General Medicine, Middle Aged, Prognosis, medicine.disease, Hodgkin Disease, Chemotherapy regimen, 3. Good health, Intestines, 030220 oncology & carcinogenesis, Colitis, Ulcerative, Female, 030211 gastroenterology & hepatology, France, Lymphoma, Large B-Cell, Diffuse, business, Immunosuppressive Agents
Abstract: Background and Aims The prognosis of lymphoma that occurs in patients with inflammatory bowel disease [IBD] is poorly known. Methods A multicentre retrospective cohort analysis was done in seven French tertiary centres from 1999 to 2019. Only lymphoma occurring in patients with previous established diagnosis of IBD were analysed. The primary outcome was progression-free survival at 3 years. Results A total of 52 patients [male 65%, Crohn’s disease 79%, median age 48.3 years, median duration of IBD 10.1 years] were included, of whom 37 had been previously exposed to immunosuppressants and/or biologics for at least 3 months and 20 had primary intestinal lymphomas. The lymphoma histological types were: diffuse large B cell lymphomas [N = 17], Hodgkin lymphomas [N = 17], indolent B cell lymphomas [N = 12], and others including T cell lymphomas, mantle cell lymphomas, and unclassifiable B cell lymphoma [N = 6]. The median follow-up after lymphoma was 5.1 years (interquartile range [IQR] 4–7.8). Progression-free survival at 3 years was 85% in the overall population (95% confidence interval [CI] 75%–96%) with no significant difference between the exposed and unexposed group, 79% for patients exposed to immunosuppressants and/or biologics [95% CI 67%–94%], and 83% for patients diagnosed with primary intestinal lymphoma [95% CI 67%–100%]. No relapse of IBD has been observed during chemotherapy. The IBD relapse rate at the end of the last chemotherapy cycle was 23% at 3 years [95% CI 11%-39%] in the overall population. Conclusions In this large cohort, the prognosis for lymphomas occurring in IBD appears to be good and similar to what is expected, irrespective of the exposure to biologics and/or immunosuppressants.
Published: 2020

27. Brain White Matter Lesions and Presumed Crohn’s Disease: Did You Consider MNGIE?

Author: Pauline Gaignard, Natalia Shor, Xavier Treton, Yann Nadjar, Vanessa Boehm, Louis Cousyn, and Robert Benamouzig
Subjects: Crohn's disease, Pathology, medicine.medical_specialty, Neurology, Brain White Matter, business.industry, Leukodystrophy, medicine, Neurology (clinical), General Medicine, medicine.disease, business
Published: 2020

28. AGR2 protein expression in colorectal tumour epithelialcompartment

Author: Eric Chevet, F Bassal, Stéphanie Beq, Benjamin Bonhomme, Emeric Boisteau, Julien Calloch, Dominique Cazals-Hatem, Frederic Delom, Delphine Fessart, Serge Evrard, Roman Hrstka, ted hupp, Astrid Lièvre, Edouard Louis, Jeremie Mariau, Marie-Alice Meuwis, Eric Ogier-Denis, Valerie Paradis, Simon Pernot, R Pineau, Xavier Treton, Valerie Velasco, Sophie Vieujean, CRLCC Eugène Marquis (CRLCC), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Thabor Therapeutics, Institut Bergonié [Bordeaux], UNICANCER, CHU Pontchaillou [Rennes], BoRdeaux Institute in onCology (Inserm U1312 - BRIC), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Edinburgh, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA-Research), Université de Liège, Centre Hospitalier Universitaire de Liège (CHU-Liège), GIGA [Université Liège], and PLBIO, Institut National Du Cancer
Subjects: COLORECTAL CANCER, SIGNAL TRANSDUCTION, Gastroenterology, [SDV.CAN]Life Sciences [q-bio]/Cancer
Published: 2022

29. Crohn's Disease

Author: Gabriel Marcellier and Xavier Treton
Subjects: Crohn's disease, medicine.medical_specialty, business.industry, Internal medicine, medicine, medicine.disease, business, Gastroenterology
Published: 2021

30. Role of adherent and invasive

Author: Anthony, Buisson, Harry, Sokol, Nassim, Hammoudi, Stéphane, Nancey, Xavier, Treton, Maria, Nachury, Mathurin, Fumery, Xavier, Hébuterne, Michael, Rodrigues, Jean-Pierre, Hugot, Gilles, Boschetti, Carmen, Stefanescu, Pauline, Wils, Philippe, Seksik, Lionel, Le Bourhis, Madeleine, Bezault, Pierre, Sauvanet, Bruno, Pereira, Matthieu, Allez, Nicolas, Barnich, and Patricia, Detre
Abstract: We used the postoperative recurrence model to better understand the role of adherent and invasiveFrom a prospective, multicentre cohort of operated patients with CD, AIEC identification was performed within the surgical specimen (M0) (N=181 patients) and the neoterminal ileum (n=119 patients/181) during colonoscopy performed 6 months after surgery (M6). Endoscopic postoperative recurrence was graded using Rutgeerts' index. The mucosa-associated microbiota was analysed by 16S sequencing at M0 and M6. Relative risks or ORs were adjusted on potential confounders.AIEC prevalence was twofold higher within the neoterminal ileum at M6 (30.3%) than within the surgical specimen (14.9%) (p0.001). AIEC within the neoterminal ileum at M6 was associated with higher rate of early ileal lesions (i1) (41.6% vs 17.1%; aRR 3.49 (95% CI 1.01 to 12.04), p=0.048) or ileal lesions (i2b+i3) (38.2% vs 17.1%; aRR 3.45 (95% CI 1.06 to 11.30), p=0.040) compared with no lesion (i0). AIEC within the surgical specimen was predictive of higher risk of i2b-endoscopic postoperative recurrence (POR) (aOR 2.54 (95% CI 1.01 to 6.44), p=0.049) and severe endoscopic POR (aOR 3.36 (95% CI 1.25 to 9.06), p=0.017). While only 5.0% (6/119) of the patients were AIEC-positive at both M0 and M6, 43.7% (52/119), patients with history of positive test for AIEC (M0 or M6) had higher risk of ileal endoscopic POR (aOR 2.32 (95% CI 1.01 to 5.39), p=0.048)), i2b-endoscopic postoperative recurrence (aOR 2.41 (95% CI 1.01 to 5.74); p=0.048) and severe endoscopic postoperative (aOR=3.84 (95% CI 1.32 to 11.18), p=0.013). AIEC colonisation was associated with a specific microbiota signature including increased abundance ofBased on the postoperative recurrence model, our data support the idea that AIEC are involved in the early steps of ileal CD.NCT03458195.
Published: 2021

31. AUTOMATIC BLEEDING AND ULCER DETECTION FROM LIMITED QUALITY ANNOTATIONS IN ULCERATIVE COLITIS

Author: Safaa Al-Ali, John Chaussard, Sébastien Li-Thiao-Té, Eric Ogier-Denis, Alice Percy-du-sert, Xavier Treton, and Hatem Zaag
Subjects: Hepatology, Gastroenterology, Immunology and Allergy
Abstract: Ulcerative colitis is an idiopathic inflammatory disorder affecting the mucosa of the colon with superficial erosions and ulcers associated with bleeding. Severity assessment using current scoring schemes such as UCEIS and MAYO relies on the subjective interpretation of the physician and fails to take into account the size of the different lesions, their number and their distribution throughout the colon. Automatic lesion detection and grading procedures can enable fine-grained assessment of lesion severity for treatment follow-up. This work aims to learn automatic bleeding and ulcer lesion detectors. As such algorithms may need to be tuned to the characteristics of the equipment used to perform the colonoscopy, we train our detectors on a dataset obtained by the Gastroenterology group at the Bichat and Beaujon hospitals. The patients’ videos were anonymous, analyzed after obtaining their consent. The study was approved by the local research study committee. To minimize expert annotation burden, only rectangular annotations are required instead of a precise delineation of lesion boundaries (Figure 1). However, this dataset contains many mislabeled pixels, especially in the corners of the rectangles. This affects the evaluation of the models’ performance and our ability to find correct models. Standard sensitivity and specificity cannot be used effectively on this dataset. We propose to evaluate model sensitivity on the annotation level and keep specificity at the pixel level. On the training set, we consider that a model correctly identifies a lesion if it agrees with the expert on a subset of the annotation, and count the detected annotations weighted by their area. For robustness and ease of interpretation, we explore the set of linear classifiers, and propose an efficient sampling scheme that rejects trivial models. This method is evaluated on a database of 10 colonoscopy videos (5 training videos and 5 test videos). In spite of the limited quality of the annotations, we find lesion detectors with a good annotation-level sensitivity (93% specificity / 89% sensitivity for bleeding and 57% specificity / 83% sensitivity for ulcers) and visual performance (see Figure 1). The detector performance is computed reliably. We evaluated sensitivity and specificity on 20 random subsets containing 10% of the images, and obtain similar performance for the same patient for all models (cf Figure 2). Figure 1. From left to right: Annotated frame and corresponding bleeding and ulcer detection with the best linear models Figure 2. Performance of the three best linear models on random subsets extracted from 5 training videos (left) and 5 test videos (right). Each ellipse corresponds to one linear model applied to a given video. Its size represents the variability (standard deviation) of sensitivity and specificity among the random subsets. However, we observe that the inter-patient performance is variable and that the best models can fail on some patients. In Figure 2, the sensitivity is below 20% is some cases. This suggests that the models are not universal because bleeding and ulcers have a different appearance in patients, and that this should be corrected before automatic detection. Alternatively, models should be adapted to the patient characteristics.
Published: 2022

32. DOP80 Effectiveness of ustekinumab and vedolizumab in patients with Crohn’s disease refractory to anti-tumour necrosis factor: A multi-centre comparative study

Author: H Alric, Julien Kirchgesner, Mathieu Allez, Antoine Meyer, Xavier Treton, Laurent Beaugerie, Yoram Bouhnik, F. Carbonnel, and Aurelien Amiot
Subjects: medicine.medical_specialty, Crohn's disease, Necrosis, business.industry, Gastroenterology, Ileum, General Medicine, medicine.disease, Vedolizumab, medicine.anatomical_structure, Refractory, Internal medicine, Ustekinumab, medicine, In patient, Multi centre, medicine.symptom, business, medicine.drug
Abstract: Background There is no head-to-head trial comparing ustekinumab and vedolizumab in patients with Crohn’s disease (CD) refractory to anti-TNF. In France between May 2014 and November 2016, vedolizumab (and not ustekinumab) was reimbursed for patients who had failed anti-TNF. Then, between December 2016 and August 2018, ustekinumab (and not vedolizumab) was reimbursed for this category of patients. Since September 2018, both ustekinumab and vedolizumab are reimbursed in patients who are refractory to anti-TNF. The aim of this study was to compare effectiveness and safety of ustekinumab and vedolizumab in patients with CD refractory to anti-TNF. Methods We studied all consecutive patients with active CD who were refractory to at least one anti-TNF, and were treated either with vedolizumab or ustekinumab, in five university hospitals of the Paris area, between May 2014 and August 2018. The primary endpoint was clinical remission rate at week 48. Adjustment according to propensity scores with inverse probability of treatment weighting was performed. Results 239 patients were included, 107 received ustekinumab and 132 received vedolizumab. After propensity scoring with IPTW, there was no difference between the two groups (Figure 1). At week 48, the clinical remission rate was higher with ustekinumab than with vedolizumab (54.4% vs. 38.3%; OR =1.92, 95% CI [1.09–3.39]). At week 48, corticosteroid-free remission rate tended to be numerically higher with ustekinumab than with vedolizumab (44.7% vs. 34.0%; OR = 1.57, 95% CI [0.88–2.79]). Treatment persistence was significantly more frequent in the ustekinumab group (71.5% vs. 49.7%; OR = 2.54, 95% CI [1.40–4.62]). The dose optimisation rate at week 48 was higher with vedolizumab than with ustekinumab (53.5% vs. 30.1%; OR = 0.37, 95% Cl [0.21–0.67]). Subgroup analyses showed that ustekinumab was associated with higher clinical remission rates at week 48 in patients with ileal CD (OR = 3.49; 95% CI [1.33–9.17]), a penetrating phenotype (OR = 6.58; 95% CI [1.91–22.68]) and a history of perianal disease (OR = 2.48; 95% CI [1.04–5.93]). Regardless of treatment group, combotherapy was associated with a higher clinical remission rate at week 48 (OR = 1.93; 95% CI [1.09–3.43]). Conclusion This study suggests that, after 1 year of follow-up, ustekinumab is associated with a higher rate of clinical remission than vedolizumab in CD patients refractory to anti-TNF, particularly in those with ileal and penetrating disease.
Published: 2020

33. 465: ROLE OF ADHERENT AND INVASIVE E. COLI IN CROHN'S DISEASE: LESSONS FROM THE POSTOPERATIVE RECURRENCE MODEL

Author: Anthony Buisson, Harry Sokol, Nassim Hammoudi, Stephane Nancey, Xavier Treton, Maria Nachury, Mathurin Fumery, Xavier Hebuterne, Michael Rodrigues, Jean-Pierre Hugot, Gilles Boschetti, Carmen Stefanescu, Pauline Wils, Philippe Seksik, Lionel Le Bourhis, Madeleine Bezault, Pierre Sauvanet, Bruno Pereira, Matthieu Allez, and Nicolas Barnich
Subjects: Hepatology, Gastroenterology
Published: 2022

34. I-FABP is decreased in COVID-19 patients, independently of the prognosis

Author: Katell Peoc'h, Alexandre Nuzzo, Xavier Treton, Mathieu Uzzan, Kevin Guedj, E. Weiss, Olivier Corcos, Damien Soudan, Catherine Trichet, Hana Manceau, and Antonino Nicoletti
Subjects: Male, Abdominal pain, Viral Diseases, Malabsorption, Pilot Projects, 030204 cardiovascular system & hematology, medicine.disease_cause, Gastroenterology, Biochemistry, 0302 clinical medicine, Medical Conditions, Medicine and Health Sciences, Respiratory system, Coronavirus, Virus Testing, Gastrointestinal tract, Multidisciplinary, Middle Aged, Prognosis, C-Reactive Proteins, Pathophysiology, Hospitals, Intensive Care Units, Infectious Diseases, Cohort, Biomarker (medicine), Medicine, 030211 gastroenterology & hepatology, Female, lipids (amino acids, peptides, and proteins), medicine.symptom, Anatomy, Research Article, medicine.medical_specialty, Science, Pain, Fatty Acid-Binding Proteins, 03 medical and health sciences, Signs and Symptoms, Diagnostic Medicine, Internal medicine, medicine, Humans, Aged, business.industry, SARS-CoV-2, Biology and Life Sciences, Proteins, COVID-19, Covid 19, medicine.disease, Abdominal Pain, Gastrointestinal Tract, Health Care, Health Care Facilities, Clinical Medicine, business, Digestive System, Biomarkers
Abstract: Background Severe acute respiratory syndrome caused by the novel coronavirus (SARS-CoV-2) is frequently associated with gastrointestinal manifestations. Herein we evaluated the interest in measuring the intestinal fatty acid-binding protein (I-FABP), a biomarker of intestinal injury, in COVID-19 patients. Methods Serum I-FABP was analyzed in 28 consecutive patients hospitalized for a PCR-confirmed COVID-19, in 24 hospitalized patients with non-COVID-19 pulmonary diseases, and 79 patients admitted to the emergency room for abdominal pain. Results I-FABP serum concentrations were significantly lower in patients with COVID-19, as compared to patients with non-COVID-19 pulmonary diseases [70.3 pg/mL (47–167.9) vs. 161.1 pg/mL (88.98–305.2), respectively, p = 0.008]. I-FABP concentrations in these two populations were significantly lower than in patients with abdominal pain without COVID-19 [344.8 pg/mL (268.9–579.6)]. I-FABP was neither associated with severity nor the duration of symptoms. I-FABP was correlated with polymorphonuclear cell counts. Conclusions In this pilot study, we observed a low I-FABP concentration in COVID-19 patients either with or without gastrointestinal symptoms, of which the pathophysiological mechanisms and clinical impact remain to be established. Further explorations on a larger cohort of patients will be needed to unravel the molecular mechanism of such observation, including the effects of malabsorption and/or abnormal lipid metabolism.
Published: 2021

35. Effectiveness and safety of ustekinumab intensification at 90 Mg every four weeks In Crohn's disease: a multicenter study

Author: Mathurin, Fumery, Laurent, Peyrin-Biroulet, Stephane, Nancey, Romain, Altwegg, Cyrielle, Gilletta, Pauline, Veyrard, Guillaume, Bouguen, Stephanie, Viennot, Florian, Poullenot, Jerome, Filippi, Anthony, Buisson, Anne, Bozon, Franck, Brazier, Lieven, Pouillon, Bernard, Flourie, Lucile, Boivineau, Laurent, Siproudhis, David, Laharie, Xavier, Roblin, Momar, Diouf, Xavier, Treton, Jonchère, Laurent, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Service d'Hépato Gastroenterologie [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), Autophagie infection et immunité - Autophagy Infection Immunity (APY), 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)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépatogastroentérologie [CHU Lyon-Sud], Hospices Civils de Lyon (HCL), Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Service de Gastroentérologie et pancréatologie [CHU Toulouse], Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de gastroentérologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Centre Hospitalier Universitaire [Rennes], Service d'Hépato-Gastro-Enterologie et Nutrition [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hépato-gastro-entérologie et oncologie digestive (CHU de Bordeaux), CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Archet 2 [Nice] (CHU), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, 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), Service Gastroentérologie [CHU Bordeaux], Centre Hospitalier Universitaire de Bordeaux (CHU Bordeaux), Direction de la recherche clinique et de l'innovation [CHU Amiens], Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de l'Environnement Industriel et des Risques, Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-CHU Saint-Eloi, Centre Hospitalier Universitaire Toulouse (CHU Toulouse), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], 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)-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), Service de Gastro-entérologie et Hépatologie [CHU Saint-Etienne], and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Crohn’s disease, [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, intensification, ustekinumab, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Abstract: International audience; Introduction: The approved maintenance regimens for ustekinumab in Crohn's disease (CD) are 90 mg every 8 or 12 weeks. Some patients will partially respond to ustekinumab or will experience a secondary loss of response. It remains poorly known if these patients may benefit from shortening the interval between injections.Methods: All patients with active CD, as defined by Harvey-Bradshaw score ≥ 4 and one objective sign of inflammation (CRP > 5 mg/L and/or fecal calprotectin > 250 µg/g and/or radiologic and/or endoscopic evidence of disease activity) who required ustekinumab dose escalation to 90mg every 4 weeks for loss of response or incomplete response to ustekinumab 90mg every 8 weeks were included in this retrospective multicenter cohort study.Results: One hundred patients, with a median age of 35 years (Interquartile Range (IQR), 28 - 49) and median disease duration of 12 (7 - 20) years were included. Dose intensification was performed after a median of 5.0 (2.8 - 9.0) months of ustekinumab treatment and was associated with corticosteroids and immunosuppressants in respectively 29% and 27% of cases. Short-term clinical response and clinical remission were observed in respectively 61% and 31% after a median of 2.4 (1.3 - 3.0) months. After a median follow-up of 8.2 (5.6-12.4) months, 61% of patients were still treated with ustekinumab, and 26% in steroid-free clinical remission. Among the 39 patients with colonoscopy during follow-up, 14 achieved endoscopic remission (no ulcers). At the end of follow-up, 27% of patients were hospitalized, and 19% underwent intestinal resection surgery. Adverse events were reported in 12% of patients, including five serious adverse events.Conclusion: In this multicenter study, two-thirds of patients recaptured response following treatment intensification with ustekinumab 90 mg every 4 weeks.
Published: 2021

36. Indications de l’autogreffe de cellules hématopoïétiques dans la Maladie de Crohn : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire

Author: Ibrahim Yakoub-Agha, Zora Marjanovic, Manuela Badoglio, David Laharie, Montserrat Rovira, Xavier Treton, M. Puyade, Miguel Torregrosa Díaz Jose, Dominique Farge, Laurent Alric, Ginette Fotsing, Grégory Pugnet, Cristina Castilla Llorente, Louis Terriou, Matthieu Allez, My-Linh Tran-Minh, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de Rangueil, CHU Toulouse [Toulouse], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Gustave Roussy (IGR), Hospital Clínic de Barcelona [Catalonia, Spain], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Claude Huriez [Lille], CHU Lille, Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Purpan [Toulouse], CHU Bordeaux [Bordeaux], Hôpital Haut-Lévêque [CHU Bordeaux], Lille Inflammation Research International Center - U 995 (LIRIC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université de Paris (UP), Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), CCSD, Accord Elsevier, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Département d'hématologie [Gustave Roussy], Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, Oncology, Mobilisation des de cellules hématopoïétiques, Cancer Research, medicine.medical_specialty, Conditionnement, medicine.drug_class, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Disease, Monoclonal antibody, Post autologous stem cell transplantation follow-up, Suivi post autogreffe, Cell therapy, 03 medical and health sciences, 0302 clinical medicine, Soins de support, Autologous hematopoietic cell transplantation, Internal medicine, Medicine, Radiology, Nuclear Medicine and imaging, Crohn's disease, Autogreffe de cellules hématopoïétiques, business.industry, Conditionning regimen, Hematopoietic stem cell, Hematology, General Medicine, Stem-cell therapy, medicine.disease, Supportive Care, Maladie de Crohn, 3. Good health, [SDV] Life Sciences [q-bio], Transplantation, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Mobilization of hematopoietic cell, Immunosuppression intensive, Methotrexate, Intensive Immunosuppression, business, medicine.drug
Abstract: International audience; Crohn's Disease (CD) is an auto-inflammatory disease, which may involve the entire gastro-intestinal tract. CD is diagnosed on several clinical, biological, endoscopic and histological criteria. First line therapy is based on oral or iv steroids. In case of steroids dependence or resistance, several types of immunosuppressive or immunomodulating therapies are available: classical antimetabolites (thiopurines or methotrexate) or monoclonal antibodies against TNFα, against interleukin 12/23 or against integrin. Nonetheless, Crohn's disease may remain active despite the use of several lines of therapy. In such cases, autologous hematopoietic cell transplantation (AHCT) is an effective therapeutic option in highly selected CD patients with specific criteria. The MATHEC-SFGM-TC Good Clinical Practice Guidelines (GCPG) were developed by a multidisciplinary group of experts including gastroenterologists, hematologists and members of the reference center for stem cell therapy in auto-immune diseases (MATHEC), including members of the French groupe d'étude thérapeutique des affections inflammatoires du tube digestif(GETAID) under the auspices of the French speaking Society of bone marrow transplantation and cellular therapy (SFGM-TC). The aim of the present guidelines is to define the eligibility criteria for CD patients when candidates to AHCT, the procedures for mobilization of hematopoietic stem cell (HSC), conditioning regimen and standardized follow-up after AHCT including monitoring of gastroenterological treatments during AHCT and thereafter throughout all follow-up.
Published: 2020

37. Vedolizumab Clinical Decision Support Tool Predicts Efficacy of Vedolizumab But Not Ustekinumab in Refractory Crohn's Disease

Author: Franck Carbonnel, Aurelien Amiot, Antoine Meyer, Yoram Bouhnik, Hadrien Alric, Mathieu Allez, Laurent Beaugerie, Xavier Treton, and Julien Kirchgesner
Subjects: medicine.medical_specialty, Antibodies, Monoclonal, Humanized, Vedolizumab, 03 medical and health sciences, 0302 clinical medicine, Refractory, Crohn Disease, Gastrointestinal Agents, Internal medicine, Ustekinumab, medicine, Immunology and Allergy, Humans, In patient, 030212 general & internal medicine, Crohn's disease, business.industry, Remission Induction, Gastroenterology, Area under the curve, University hospital, medicine.disease, Decision Support Systems, Clinical, Treatment Outcome, 030211 gastroenterology & hepatology, Tumor Necrosis Factor Inhibitors, business, medicine.drug
Abstract: Introduction Vedolizumab clinical decision support tool (VDZ-CDST) predicts response to vedolizumab, but whether this tool also predicts efficacy of other drugs in Crohn’s disease (CD) is unknown. This study aimed to assess the value of VDZ-CDST to predict vedolizumab and ustekinumab efficacy in patients with CD. Patients and methods We included consecutive CD patients refractory or intolerant to anti-TNF who started either vedolizumab or ustekinumab in 5 university hospitals between May 2014 and August 2018. The main end points were the rates of clinical remission and steroid-free clinical remission (SFCR) in each group of VDZ-CDST at week 48. Results One hundred eighty patients were included; 94 received vedolizumab (VDZ-CDST ≤13: 32; VDZ-CDST >13 and ≤19: 52; VDZ-CDST >19: 10), and 86 received ustekinumab (VDZ-CDST ≤13: 16; VDZ-CDST >13 and ≤19: 60; VDZ-CDST >19: 10). At week 48 in the vedolizumab group, clinical remission and SFCR were reached in 9.4% with a VDZ-CDST ≤13, in 38.5% and 28.8% with a VDZ-CDST >13 and ≤19, respectively, and in 80.0% with a VDZ-CDST >19 (P 13 and ≤19, and 50.0% with a VDZ-CDST >19, respectively (P = 0.65 and P = 0.46, respectively). VDZ-CDST identified SFCR with an area under the curve of 0.69 (95% CI, 0.57–0.82) for vedolizumab and 0.52 (95% CI, 0.40–0.65) for ustekinumab. Conclusion The VDZ-CDST predicts clinical remission and SFCR at week 48 for vedolizumab but not for ustekinumab in CD patients refractory or intolerant to anti-TNF.
Published: 2020

38. P672 A tertiary multicenter cohort of patients with chronic intestinal pseudo-obstruction and Crohn’s disease: a rare association with a high prevalence of monogenic disorders

Author: Dominique Cazals-Hatem, Mathieu Uzzan, L Billiauws, Y. Bouhnik, Carmen Stefanescu, Xavier Treton, F Joly, Nadine Cerf-Bensussan, Olivier Goulet, F De castelbajac, and Fabienne Charbit-Henrion
Subjects: Intestinal pseudo-obstruction, medicine.medical_specialty, Crohn's disease, Cryptitis, business.industry, Gastroenterology, General Medicine, medicine.disease, Inflammatory bowel disease, Vedolizumab, Internal medicine, Ustekinumab, Cohort, medicine, business, Irritable bowel syndrome, medicine.drug
Abstract: Background Chronic intestinal pseudo-obstruction (CIPO) is a rare condition that is not commonly associated with Crohn’s disease (CD). We performed a cohort study aiming at identifying clinical, immunological and genetic features as well as response to conventional CD treatments of patients co-affected with CIPO and CD. Methods We conducted an observational retrospective cohort study in two tertiary CIPO and IBD centers. Patients with parenteral nutrition-dependent CIPO and features of CD including large intestinal or perianal ulcers, strictures, abscesses and fistula with pathology findings compatible with CD, were included. We used flow-cytometry and targeted-next generation sequencing to identify immune defects and monogenic causes in 129 predefined genes responsible for monogenic enteropathies Results Eight unrelated patients were studied. 5 had a myogenic phenotype and 3 had a neurogenic form with histological exam for all patients. CD involved small bowel in all cases whereas one patient had ileocolonic involvement. Two patients had perianal complex fistula. Seven patients had a stricturing form and 1 had an inflammatory-only behavior. No patient had a penetrating form. All patients were diagnosed with CIPO prior to CD. Median age at CIPO diagnosis was 11.5 years old (IQR 0,31.5) while it was 22.5 (IQR 19,29) at CD diagnosis. At CD diagnosis, mean fecal calprotectin level was 551 ug/g (range 390 - 1200) and citrulline averaged 23.6 umol/l (range 15–35 umol/l). Histopathological analyses of intestinal specimens revealed ulcerations for half of the patients, increase in intraepithelial lymphocytes in 3, granuloma and cryptitis in 1 patient. Abnormalities in peripheral lymphocytes’ subsets were found in 2 patients. 5 patients were ultimately diagnosed with monogenic forms of enteropathy: 2 in ACTG2, with an autosomal dominant inheritance, 1 with a STAT1gain of function, (GOF) and two with recessive inheritance: TYMP. All patients received steroids with clinical response in 2. 6 patients received antiTNF, with only one sustained remission. Two patients received vedolizumab and 2 were treated with ustekinumab. Except for antiTNF in 1 patient, common CD treatments did not lead to any improvement. Of note, antiJAK therapy in a patient with STAT1GOF failed to induce remission. Conclusion Herein is described the first cohort of extensively genetically and immunologically explored patients co-affected with CIPO and CD. Immune defects were common and monogenic forms were found with a high prevalence. Rates of response to biologic treatment were very low. Identification of monogenic cause through immunological and genetic explorations is warranted in patient with CIPO-CD association as it could lead to targeted therapy and genetic counseling.
Published: 2021

39. Real-world use of therapeutic drug monitoring of CT-P13 in patients with inflammatory bowel disease: A 12-month prospective observational cohort study

Author: Pauline Jouet, Laurent Beaugerie, Anne-Laure Pelletier, Robert Benamouzig, Xavier Amiot, Nicolas Petitdidier, Georgia Malamut, Vered Abitbol, Xavier Treton, Aurelien Amiot, Lysiane Marthey, Matthieu Allez, Franck Carbonnel, Yoram Bouhnik, Sylvie Rajca, Anne Bourrier, Early detection of Colon Cancer using Molecular Markers and Microbiota (EA 7375) (EC2M3), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Hépato-gastro-entérologie [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, [SDV]Life Sciences [q-bio], Inflammatory bowel disease, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Trough Concentration, Prospective Studies, Crohn's disease, Hepatology, medicine.diagnostic_test, business.industry, Gastroenterology, Antibodies, Monoclonal, Middle Aged, Inflammatory Bowel Diseases, medicine.disease, Ulcerative colitis, Infliximab, 3. Good health, Therapeutic drug monitoring, 030220 oncology & carcinogenesis, Cohort, Female, 030211 gastroenterology & hepatology, Drug Monitoring, business, Cohort study, medicine.drug
Abstract: Summary Background Whether therapeutic drug monitoring (TDM) of infliximab should be implemented in daily practice is an ongoing controversy. Aims To assess the real-world use of TDM in an observational multicentre cohort study with consecutive patients with inflammatory bowel disease (IBD) treated with CT-P13. Methods Between September 2015 and December 2016, 364 patients with IBD were treated with CT-P13 in 13 gastroenterology departments and were followed up for 54 weeks. Disease activity, CT-P13 trough concentration and anti-CT-P13 antibody (ACA) were recorded. Results Steroid-free clinical remission rates at week 54 were 67.0% and 56.4% in patients with CD and UC, respectively. CT-P13 trough concentrations were measured in 70.7% of the patients. The mean CT-P13 trough concentration was 4.2 ± 4.3 μg/mL. The presence of ACA was observed in 53 (15.9%) patients. CT-P13 trough concentration was collected in a proactive approach in 62.8% of cases and in a reactive approach in 37.2%. Among patients who submitted to TDM, CT-P13 therapy was optimized in 88.7% of the reactive group and in 22.5% of the proactive group (P Conclusion In a real-world cohort of patients with IBD treated with CT-P13, more than two-thirds of the patients underwent TDM. CT-P13 optimization was much less common in the proactive approach than in the reactive approach.
Published: 2020

40. Computational Learning of microRNA-Based Prediction of Pouchitis Outcome After Restorative Proctocolectomy in Patients With Ulcerative Colitis

Author: Gilles Boschetti, Ian Morilla, Dominique Cazals-Hatem, Yves Panis, Mathieu Uzzan, Aurelien Amiot, Nathalie Colnot, Stéphane Nancey, Fanny Daniel, Eric Ogier-Denis, and Xavier Treton
Subjects: Oncology, medicine.medical_specialty, medicine.medical_treatment, Colonic Pouches, Pouchitis, Internal medicine, medicine, Immunology and Allergy, Humans, Colectomy, Retrospective Studies, Proctocolectomy, business.industry, Proctocolectomy, Restorative, Gastroenterology, Area under the curve, Retrospective cohort study, medicine.disease, Ulcerative colitis, MicroRNAs, Cohort, Biomarker (medicine), Colitis, Ulcerative, business, Biomarkers
Abstract: Background Ileal pouch-anal anastomosis (IPAA) is the standard of care after total proctocolectomy for ulcerative colitis (UC). However, inflammation often develops in the pouch, leading to acute or recurrent/chronic pouchitis (R/CP). MicroRNAs (miRNA) are used as accurate diagnostic and predictive biomarkers in many human diseases, including inflammatory bowel diseases. Therefore, we aimed to identify an miRNA-based biomarker to predict the occurrence of R/CP in patients with UC after colectomy and IPAA. Methods We conducted a retrospective study in 3 tertiary centers in France. We included patients with UC who had undergone IPAA with or without subsequent R/CP. Paraffin-embedded biopsies collected from the terminal ileum during the proctocolectomy procedure were used for microarray analysis of miRNA expression profiles. Deep neural network–based classifiers were used to identify biomarkers predicting R/CP using miRNA expression and relevant biological and clinical factors in a discovery cohort of 29 patients. The classification algorithm was tested in an independent validation cohort of 28 patients. Results A combination of 11 miRNA expression profiles and 3 biological/clinical factors predicted the outcome of R/CP with 88% accuracy (area under the curve = 0.94) in the discovery cohort. The performance of the classification algorithm was confirmed in the validation cohort with 88% accuracy (area under the curve = 0.90). Apoptosis, cytoskeletal regulation by Rho GTPase, and fibroblast growth factor signaling were the most dysregulated targets of the 11 selected miRNAs. Conclusions We developed and validated a computational miRNA-based algorithm for accurately predicting R/CP in patients with UC after IPAA.
Published: 2020

41. Patients with COVID-19 present with low plasma citrulline concentrations that associate with systemic inflammation and gastrointestinal symptoms

Author: Mathieu Uzzan, Damien Soudan, Xavier Treton, Olivier Corcos, E. Weiss, and Katell Peoc'h
Subjects: Diarrhea, Male, Low plasma citrulline, Coronavirus disease 2019 (COVID-19), Vomiting, Pneumonia, Viral, Systemic inflammation, Severity of Illness Index, Article, Betacoronavirus, Olfaction Disorders, Severity of illness, Pandemic, Medicine, Humans, Prospective Studies, Prospective cohort study, Pandemics, Serum Albumin, Aged, Inflammation, Hepatology, biology, business.industry, SARS-CoV-2, Gastroenterology, COVID-19, Nausea, Middle Aged, biology.organism_classification, medicine.disease, Abdominal Pain, Anorexia, Pneumonia, C-Reactive Protein, Immunology, Ferritins, Citrulline, Female, medicine.symptom, business, Ageusia, Coronavirus Infections
Published: 2020

42. The outcome of Crohn's disease patients refractory to anti-TNF and either vedolizumab or ustekinumab

Author: Liza Kassouri, Yoram Bouhnik, Franck Carbonnel, Xavier Treton, Mathieu Allez, Laurent Beaugerie, Aurelien Amiot, Julien Kirchgesner, and Antoine Meyer
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Antibodies, Monoclonal, Humanized, Vedolizumab, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Refractory, Crohn Disease, Gastrointestinal Agents, Internal medicine, Ustekinumab, medicine, Humans, Treatment Failure, Proportional Hazards Models, Retrospective Studies, Crohn's disease, Hepatology, Proportional hazards model, business.industry, Tumor Necrosis Factor-alpha, Hazard ratio, Remission Induction, Gastroenterology, Retrospective cohort study, medicine.disease, Confidence interval, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, business, medicine.drug
Abstract: Aims The aims of this study were to describe outcomes in patients with Crohn's disease who fail anti-tumor necrosis factor (TNF) and either vedolizumab or ustekinumab. Methods Multicenter, retrospective study of 100 patients with Crohn's disease who failed anti-TNF and either vedolizumab or ustekinumab from 2015 to 2019. Using multivariable Cox regression, we sought to identify factors associated with need for surgery. Results 75 patients received a third line treatment, resulting in 23 (30.7%) clinical remission at week 48. Among the 71 patients included after vedolizumab failure, 46 received ustekinumab, resulting in 46 (28.3%) clinical remission; 13 patients were retreated with an anti-TNF, resulting in 13 (46.2%) clinical remission. Among the 29 patients included after ustekinumab failure, 12 were retreated with an anti-TNF, resulting in 2 (16.7%) clinical remission. The rate of surgery-free survival at 48 weeks was 76.5% (95% confidence interval 68.4% - 85.4%). In multivariable analysis, ileal disease localization (hazard ratio 9.0, 95% confidence interval 1.0–81.9) was associated with a higher risk of surgery. Conclusion In patients with Crohn's disease who have failed anti-TNF and either vedolizumab or ustekinumab, at week 48, the surgery rate is 23.5% and the remission rate after a third line biologic therapy is 30.7%.
Published: 2020

43. Impact of panelists' experience on script concordance test scores of medical students

Author: Jennifer Truchot, Sylvie Chevret, Pierre-Emmanuel Cailleaux, Jonathan Messika, Mariana Mirabel, Victoria Tea, Alice Hutin, David Calvet, Raphael Borie, Yousrah Baadj, Adrien Albaladejo, David Lebeaux, Martin Flamant, Alexandre Meunier, Xavier Treton, Damien Roux, Olivier Peyrony, and Clémence Martin
Subjects: Medical knowledge, medicine.medical_specialty, Students, Medical, 020205 medical informatics, Wilcoxon signed-rank test, Concordance, lcsh:Medicine, 02 engineering and technology, Statistics, Nonparametric, Education, 03 medical and health sciences, 0302 clinical medicine, 0202 electrical engineering, electronic engineering, information engineering, medicine, Humans, 030212 general & internal medicine, Experience level, Medical student, Median score, Medical education, lcsh:LC8-6691, Script concordance test, lcsh:Special aspects of education, business.industry, lcsh:R, Clinical reasoning, Uncertainty, General Medicine, Panelist, Test (assessment), Large cohort, Physical therapy, Clinical Competence, Educational Measurement, business, Research Article
Abstract: Background The evaluation process of French medical students will evolve in the next few years in order to improve assessment validity. Script concordance testing (SCT) offers the possibility to assess medical knowledge alongside clinical reasoning under conditions of uncertainty. In this study, we aimed at comparing the SCT scores of a large cohort of undergraduate medical students, according to the experience level of the reference panel. Methods In 2019, the authors developed a 30-item SCT and sent it to experts with varying levels of experience. Data analysis included score comparisons with paired Wilcoxon rank sum tests and concordance analysis with Bland & Altman plots. Results A panel of 75 experts was divided into three groups: 31 residents, 21 non-experienced physicians (NEP) and 23 experienced physicians (EP). Among each group, random samples of N = 20, 15 and 10 were selected. A total of 985 students from nine different medical schools participated in the SCT examination. No matter the size of the panel (N = 20, 15 or 10), students’ SCT scores were lower with the NEP group when compared to the resident panel (median score 67.1 vs 69.1, p p N = 15 and 67.7 vs 68.4, p N = 10) and with EP compared to NEP (65.4 vs 67.1, p p p Conclusions Even though student SCT scores differed statistically according to the expert panels, these differences were rather weak. These results open the possibility of including less-experienced experts in panels for the evaluation of medical students.
Published: 2020

44. Prominence of ileal mucosa-associated microbiota to predict postoperative endoscopic recurrence in Crohn’s disease

Author: Philippe Seksik, Xavier Treton, Mathurin Fumery, Claire Auzolle, Nicolas Barnich, Lionel Le Bourhis, Benjamin Pariente, Anthony Buisson, Loic Brot, Stéphane Nancey, Harry Sokol, Carmen Stefanescu, Matthieu Allez, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), INSERM, U1160, Département de Gastroentérologie, Université Paris Diderot - Paris 7 (UPD7), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Clermont-Ferrand, CHU Amiens-Picardie, Hôpital Claude Huriez [Lille], CHU Lille, Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Autophagie infection et immunité - Autophagy Infection Immunity (APY), 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)-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), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), INSERM UMR-S 606, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, PRES Sorbonne Paris-Cité, and Université Paris Denis Diderot, This study has been supported by grants from MSD France, Association Francois Aupetit, the Helmsley Charitable Trust and Inserm., Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AgroParisTech, Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de la Recherche Agronomique (INRA), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Centre Hospitalier Universitaire Clermont Ferrand, Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Autophagie infections immunité – Autophagy Infection Immunity, 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)-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), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: Adult, Male, medicine.medical_specialty, Firmicutes, Disease, Gut flora, Gastroenterology, digestive system, Endoscopy, Gastrointestinal, Ileal resection, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Crohn Disease, Ileum, Recurrence, Risk Factors, Internal medicine, Proteobacteria, medicine, microbiota, Humans, Postoperative Period, Prospective Studies, Intestinal Mucosa, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Crohn's disease, biology, business.industry, Lachnospiraceae, Healthy subjects, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, mucosa-associated, Middle Aged, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Gastrointestinal Microbiome, Cohort, 030211 gastroenterology & hepatology, Female, business, Ileal mucosa
Abstract: ObjectiveFollowing ileal resection for Crohn’s disease (CD), recurrence is very frequent. Although several clinical risk factors of recurrence have been identified, predicting relapse remains challenging. Performing an ileocolonoscopy within the first year after surgery is currently recommended to assess endoscopic recurrence and to adjust the treatment. We took advantage of a large prospective multicentric cohort to investigate the role of the ileal mucosa-associated microbiota in postoperative endoscopic recurrence.Patients and methodsIleal mucosa-associated microbiota was analysed by 16S sequencing at the time of surgery and/or of endoscopic evaluation in 201 patients (288 samples in total) prospectively recruited in France.ResultsIleal mucosa-associated microbiota exhibits profound changes following surgery in CD. Compared with non-recurrence setting, endoscopic recurrence is associated with strong changes in ileal mucosa-associated microbiota that are highly reminiscent of those observed generally in ileal CD compared with healthy subjects with a reduction in alpha diversity, an increase in several members of the Proteobacteria phylum and a decrease in several members of the Lachnospiraceae and the Ruminococcaceae families within the Firmicutes phylum. At the time of surgery, we identified several bacterial taxa associated with endoscopic recurrence and that can better predict relapse than usual clinical risk factors.ConclusionSurgery has an important impact on ileal mucosa-associated microbiota. Postoperative endoscopic recurrence is associated with changes in microbiota composition and alpha diversity. The gut microbiota has the potential to predict postoperative evolution and recurrence.
Published: 2020

45. Segmental colectomy for ulcerative colitis: is there a place in selected patients without active colitis ? An international multicentric retrospective study in 72 patients

Author: Xavier Treton, Edouard Louis, Silvio Danese, Q Denost, Fabrizio Michelassi, V Bridoux, Gianluca M. Sampietro, D. Laharie, Pär Myrelid, Gilberto Poggioli, E Espin, Philippe Zerbib, Stéphane Nancey, Romain Altwegg, Giuseppe S. Sica, L Cohen, L Beyer-Berjot, Yves Panis, Matteo Frasson, Antonino Spinelli, Mathurin Fumery, A. Frontali, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de chirurgie digestive [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Linköping University (LIU), PoliclinicoTor Vergata - Fondatione PTV, Policlinico S. Orsola-malpighi, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO)-Servizio sanitario regionale Emilia-Romagna, Vall d'Hebron University Hospital [Barcelona], Assistance Publique - Hôpitaux de Marseille (APHM), CHU Bordeaux [Bordeaux], Department of Colorectal Surgery, Humanitas Research Hospital, Milano, Italy., Hôpital Claude Huriez [Lille], CHU Lille, Department of Surgery, IBD Unit, Luigi Sacco University Hospital, Milano, Italy., University Hospital La Fe, Digestive Surgery, Valencia, Spain., Centre Hospitalier Universitaire de Liège (CHU-Liège), Department of Gastroenterology, Humanitas Research Hospital, Milano, Italy., Registre EPIMAD, Normandie Université (NU)-Normandie Université (NU)-CHU Amiens-Picardie-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, CHU Pessac, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Agogo Presbyterian Hospital [GHANA], Frontali, A, Cohen, L, Bridoux, V, Myrelid, P, Sica, G, Poggioli, G, Espin, E, Beyer-Berjot, L, Laharie, D, Spinelli, A, Zerbib, P, Sampietro, G, Frasson, M, Louis, E, Danese, S, Fumery, M, Denost, Q, Altwegg, R, Nancey, S, Michelassi, F, Treton, X, Panis, Y, Frontali A., Cohen L., Bridoux V., Myrelid P., Sica G., Poggioli G., Espin E., Beyer-Berjot L., Laharie D., Spinelli A., Zerbib P., Sampietro G., Frasson M., Louis E., Danese S., Fumery M., Denost Q., Altwegg R., Nancey S., Michelassi F., Treton X., and Panis Y.
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, segmental colectomy, postoperative flare, Anastomosis, Gastroenterology, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Sigmoidectomy, Internal medicine, Humans, Medicine, Colitis, Child, Colectomy, ulcerative colitis, Aged, Retrospective Studies, Aged, 80 and over, business.industry, postoperative flare, segmental colectomy, ulcerative colitis, Segmental colectomy, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Retrospective cohort study, General Medicine, Middle Aged, Diverticulitis, medicine.disease, Ulcerative colitis, Settore MED/18, 3. Good health, Dysplasia, 030220 oncology & carcinogenesis, Right Colectomy, Colitis, Ulcerative, Female, 030211 gastroenterology & hepatology, business
Abstract: Background and Aims The aim of this study was to report a multicentric experience of segmental colectomy [SC] in ulcerative colitis [UC] patients without active colitis, in order to assess if SC can or cannot represent an alternative to ileal pouch-anal anastomosis [IPAA]. Methods All UC patients undergoing SC were included. Postoperative complications according to ClavienDindo’s classification, long term results, and risk factors for postoperative colitis and reoperation for colitis on the remnant colon, were assessed. Results: A total of 72 UC patients underwent: sigmoidectomy [n = 28], right colectomy [n = 24], proctectomy [n = 11], or left colectomy [n = 9] for colonic cancer [n = 27], ‘diverticulitis’ [n = 17], colonic stenosis [n = 5], dysplasia or polyps [n = 8], and miscellaneous [n = 15]. Three patients died postoperatively and 5/69 patients [7%] developed early flare of UC within 3 months after SC. After a median followup of 40 months, 24/69 patients [35%] were reoperated after a median delay after SC of 19 months [range, 2–158 months]: 22/24 [92%] underwent total colectomy and ileorectal anastomosis [n = 9] or total coloproctectomy [TCP] [n = 13] and 2/24 [8%] an additional SC. Reasons for reoperation were: colitis [n = 14; 20%], cancer [n = 3] or dysplasia [n = 3], colonic stenosis [n = 1], and unknown reasons [n = 3]. Endoscopic score of colitis before SC was Mayo 23 in 5/5 [100%] patients with early flare vs 15/42 without early flare [36%; p = 0.0101] and in 9/12 [75%] patients with reoperation for colitis vs 11/35 without reoperation [31%; p = 0.016]. Conclusions After segmental colectomy in UC patients, postoperative early colitis is rare [7%]. Segmental colectomy could possibly represent an alternative to IPAA in selected UC patients without active colitis.
Published: 2020

46. Postoperative Endoscopic Recurrence on the Neoterminal Ileum But Not on the Anastomosis Is Mainly Driving Long-Term Outcomes in Crohn's Disease

Author: Madeleine Bezault, Philippe Seksik, Mathurin Fumery, Nassim Hammoudi, Benjamin Pariente, Anthony Buisson, Stéphane Nancey, Claire Auzolle, Lionel Le Bourhis, Gilles Boschetti, My-Linh Tran Minh, Xavier Treton, Matthieu Allez, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Crohn's disease, medicine.medical_specialty, Hepatology, medicine.diagnostic_test, business.industry, Gold standard, Gastroenterology, Ileum, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Anastomosis, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Endoscopy, Surgery, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Interquartile range, 030220 oncology & carcinogenesis, medicine, Long term outcomes, 030211 gastroenterology & hepatology, In patient, business, ComputingMilieux_MISCELLANEOUS
Abstract: Early ileocolonoscopy within the first year after surgery is the gold standard to evaluate recurrence after ileocolonic resection for Crohn's disease (CD). The aim of the study was to evaluate the association between the presence and severity of anastomotic and ileal lesions at early postoperative ileocolonoscopy and long-term outcomes. The REMIND group conducted a prospective multicenter study. Patients operated for ileal or ileocolonic CD were included. An ileocolonoscopy was performed 6 months after surgery. An endoscopic score describing separately the anastomotic and ileal lesions was built. Clinical relapse was defined by the CD-related symptoms, confirmed by imaging, endoscopy or therapeutic intensification; CD-related complications; or subsequent surgery. Among 225 included patients, long-term follow-up was available in 193 (median follow-up: 3.82 years [interquartile range: 2.56-5.41]). Median clinical recurrence-free survival was 47.6 months. Clinical recurrence-free survival was significantly shorter in patients with ileal lesions at early postoperative endoscopy whatever their severity was (I(1) or I(2,3,4)) as compared to patients without ileal lesions (I(0)) (I(0) vs I(2,3,4): P = 0.0003; I(0) vs I(1): P = 0.0008 and I(1) vs I(2,3,4): P = 0.43). Patients with exclusively ileal lesions (A(0)I(1,2,3,4)) had poorer clinical long-term outcomes than patients with exclusively anastomotic lesions (A(1,2,3)I(0)) (P = 0.009). A score describing separately the anastomotic and ileal lesions might be more appropriate to define postoperative endoscopic recurrence. Our data suggest that patients with ileal lesions, including mild ones (I(1)), could beneficiate from treatment step-up to improve long-term outcomes.
Published: 2020

47. Immune-checkpoint inhibitor anti-PD1 aggravates colitis-associated colorectal cancer without enhancing intestinal inflammation

Author: Eric Ogier-Denis, Xavier Treton, Nathalie Guedj, Léon Maggiori, M. Albuquerque, Yves Panis, Pascal Hammel, M. Collard, and Julien Tourneur-Marsille
Subjects: Colorectal cancer, Intestinal inflammation, business.industry, Immune checkpoint inhibitors, medicine, Cancer research, Colitis, medicine.disease, Anti pd1, business
Published: 2020

48. T cell clonal expansions in ileal Crohn’s disease are associated with smoking behaviour and postoperative recurrence

Author: Benjamin Pariente, Azucena Salas, Xavier Treton, Matthieu Allez, Stéphane Nancey, Victor Chardiny, Anthony Buisson, Mathurin Fumery, Harry Sokol, Nicolas Barnich, Marjolaine Ngollo, Hugo Bottois, Carmen Stefanescu, Philippe Seksik, Ana Maria Corraliza, Claire Auzolle, Lionel Le Bourhis, Kevin Perez, Service d'hépato-gastro-entérologie, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), INSERM, U1160, Département de Gastroentérologie, Université Paris Diderot - Paris 7 (UPD7), Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon, Autophagie infections immunité – Autophagy Infection Immunity, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Département d'Hépato-Gastroentérologie, Hôtel-Dieu-CHU Clermont-Ferrand-Université de Clermont-Ferrand, Service d'Hépato-gastroentérologie, Hôpital Huriez-Université de Lille, Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Autophagie infection et immunité - Autophagy Infection Immunity (APY), 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)-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), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Helmsley Charitable Trust Association Francois Aupetit MSD France laboratories, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], 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)-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), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de la Recherche Agronomique (INRA)
Subjects: Adult, Male, medicine.medical_specialty, Microarray, T cell, Receptors, Antigen, T-Cell, Gastroenterology, Cohort Studies, Pathogenesis, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Recurrence, Internal medicine, medicine, Humans, Cytotoxic T cell, Postoperative Period, Intestinal Mucosa, ComputingMilieux_MISCELLANEOUS, Aged, 030304 developmental biology, 0303 health sciences, Crohn's disease, medicine.diagnostic_test, business.industry, Smoking, T-cell receptor, Area under the curve, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Ileitis, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Endoscopy, Treatment Outcome, medicine.anatomical_structure, Female, 030211 gastroenterology & hepatology, business
Abstract: T cell clonal expansions are present in the inflamed mucosa of patients with Crohn’s disease (CD) and may be implicated in postoperative recurrence after ileocolonic resection.MethodsT cell receptor (TCR) analysis was performed in 57 patients included in a prospective multicentre cohort. Endoscopic recurrence was defined by a Rutgeerts score >i0. DNA and mRNA were extracted from biopsies collected from the surgical specimen and endoscopy, and analysed by high throughput sequencing and microarray, respectively.ResultsTCR repertoire in the mucosa of patients with CD displayed diverse clonal expansions. Active smokers at time of surgery had a significantly increased proportion of clonal expansions as compared with non-smokers (25.9%vs17.9%, p=0.02). The percentage of high frequency clones in the surgical specimen was significantly higher in patients with recurrence and correlated with postoperative endoscopic recurrence (area under the curve (AUC) 0.69, 95% CI 0.54 to 0.83). All patients with clonality above 26.8% (18/57) had an endoscopic recurrence. These patients with a high clonality were more frequently smokers than patients with a low clonality (61% vs 23%, p=0.005). The persistence of a similar TCR repertoire at postoperative endoscopy was associated with smoking and disease recurrence. Patients with high clonality showed increased expression of genes associated with CD8 T cells and reduced expression of inflammation-related genes. Expanded clones were found predominantly in the CD8 T cell compartment.ConclusionClonal T cell expansions are implicated in postoperative endoscopic recurrence. CD patients with increased proportion of clonal T cell expansions in the ileal mucosa represent a subgroup associated with smoking and where pathogenesis appears as T cell driven.Trial registration numberNCT03458195.
Published: 2019

49. The effectiveness of either ustekinumab or vedolizumab in 239 patients with Crohn's disease refractory to anti-tumour necrosis factor

Author: Julien Kirchgesner, Yoram Bouhnik, Aurelien Amiot, Franck Carbonnel, Antoine Meyer, Laurent Beaugerie, Xavier Treton, Hadrien Alric, and Matthieu Allez
Subjects: Adult, Male, medicine.medical_specialty, Combination therapy, Antibodies, Monoclonal, Humanized, Gastroenterology, Vedolizumab, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Refractory, Crohn Disease, Internal medicine, Ustekinumab, Medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Retrospective Studies, Crohn's disease, Hepatology, business.industry, Tumor Necrosis Factor-alpha, Retrospective cohort study, Odds ratio, Middle Aged, medicine.disease, 030211 gastroenterology & hepatology, Female, business, Cohort study, medicine.drug
Abstract: Background There is no head-to-head trial comparing ustekinumab and vedolizumab in patients with Crohn's disease (CD) refractory to anti-tumour necrosis factor (anti-TNF). Aim To compare the effectiveness and safety of ustekinumab and vedolizumab in patients with CD refractory to anti-TNF in a multicentre retrospective observational cohort. Methods All consecutive patients with CD refractory or intolerant to anti-TNF who initiated either vedolizumab or ustekinumab were included between May 2014 and August 2018. Clinical remission, steroid-free clinical remission (SFCR) and treatment persistence were assessed at week 48 with intention-to-treat analysis and propensity scores weighted comparison. Results A total of 239 patients were included, 107 received ustekinumab and 132 received vedolizumab. At week 48, ustekinumab was associated with a higher clinical remission rate (54.4% vs 38.3%; odds ratios, OR = 1.92, 95% CI [1.09-3.39]) and treatment persistence (71.5% vs 49.7%; OR = 2.54, 95% CI [1.40-4.62]) than vedolizumab. The rate of SFCR did not differ significantly between ustekinumab and vedolizumab (44.7% vs 34.0%; OR = 1.57, 95% CI [0.88-2.79]). Subgroup analyses showed that ustekinumab was associated with a higher clinical remission rates at week 48 in patients with ileal location (OR = 3.49, 95% CI [1.33-9.17) and penetrating behaviour (OR = 6.58, 95% CI [1.91-22.68]). Regardless of the treatment group, combination therapy at initiation was associated with a higher clinical remission rate at week 48 (OR = 1.93, 95% CI [1.09-3.43]). Conclusion This study suggests that ustekinumab is associated with a higher rate of clinical remission and treatment persistence than vedolizumab after 48 weeks of follow-up, in patients with CD refractory or intolerant to anti-TNF. The rate of SFCR was not significantly different.
Published: 2019

50. Endoscopic training: A nationwide survey of French fellows in gastroenterology

Author: Maxime Palazzo, Jérôme Winkler, Yann Le Baleur, Aurelien Amiot, Guillaume Conroy, and Xavier Treton
Subjects: Adult, Male, medicine.medical_specialty, genetic structures, Attitude of Health Personnel, Nationwide survey, Gastroenterology, Endoscopy, Gastrointestinal, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Fellowships and Scholarships, Self report, Hepatology, medicine.diagnostic_test, business.industry, Independent factor, Threshold number, Endoscopy, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, France, Self Report, business, Endoscopic training
Abstract: Summary Background During their 4 years of training, French fellows in gastroenterology should acquire theoretical and practical competency in gastrointestinal (GI) endoscopy. Aims To evaluate the delivery of endoscopy training to French GI fellows and perception of learning. Methods A nationwide electronic survey was carried out of French GI fellows using an anonymous, 17-item electronic questionnaire. Results A total of 291 out of 484 (60%) GI fellows responded to the survey. Only 40% of subjects had access to theoretical training and/or virtual simulators. Only 49% and 35% of fourth year fellows had reached the threshold numbers of EGD and colonoscopies recommended by the European section and Board of gastroenterology and hepatology. Sixty-two percent and 57% of trainees reported having insufficient knowledge in interpreting gastric and colic lesions. Access to dedicated endoscopy activity for at least 8 weeks during the year was the only independent factor associated with the achievement of the recommended annual threshold number of procedures. Conclusion The access of fellows to theoretical training and to preclinical virtual simulators is still insufficient. Personalized support and regular assessment of cognitive and technical acquisition over the 4 years of training seems to be necessary.
Published: 2018

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