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1. SMAD4 TGF-β–independent function preconditions naive CD8+ T cells to prevent severe chronic intestinal inflammation

Author

Ramdane Igalouzene, Hector Hernandez-Vargas, Nicolas Benech, Alexandre Guyennon, David Bauché, Célia Barrachina, Emeric Dubois, Julien C. Marie, and Saïdi M’Homa Soudja

Subjects
Gastroenterology, Immunology, Medicine
Abstract

SMAD4, a mediator of TGF-β signaling, plays an important role in T cells to prevent inflammatory bowel disease (IBD). However, the precise mechanisms underlying this control remain elusive. Using both genetic and epigenetic approaches, we revealed an unexpected mechanism by which SMAD4 prevents naive CD8+ T cells from becoming pathogenic for the gut. Prior to the engagement of the TGF-β receptor, SMAD4 restrains the epigenetic, transcriptional, and functional landscape of the TGF-β signature in naive CD8+ T cells. Mechanistically, prior to TGF-β signaling, SMAD4 binds to promoters and enhancers of several TGF-β target genes, and by regulating histone deacetylation, suppresses their expression. Consequently, regardless of a TGF-β signal, SMAD4 limits the expression of TGF-β negative feedback loop genes, such as Smad7 and Ski, and likely conditions CD8+ T cells for the immunoregulatory effects of TGF-β. In addition, SMAD4 ablation conferred naive CD8+ T cells with both a superior survival capacity, by enhancing their response to IL-7, as well as an enhanced capacity to be retained within the intestinal epithelium, by promoting the expression of Itgae, which encodes the integrin CD103. Accumulation, epithelial retention, and escape from TGF-β control elicited chronic microbiota-driven CD8+ T cell activation in the gut. Hence, in a TGF-β–independent manner, SMAD4 imprints a program that preconditions naive CD8+ T cell fate, preventing IBD.

Published
2022
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2. Fecal microbiota transplantation in gastrointestinal disorders: time for precision medicine

Author

Nicolas Benech and Harry Sokol

Subjects
Fecal microbiota transplantation, Precision medicine, Inflammatory bowel diseases, Irritable bowel syndrome, Medicine, Genetics, QH426-470
Abstract

Abstract Fecal microbiota transplantation (FMT) has demonstrated efficacy in treating inflammatory bowel diseases and irritable bowel syndrome in an increasing number of randomized controlled trials. Recently published data gives striking insights into the factors associated with FMT success paving the road for the use of precision medicine in gastrointestinal disorders.

Published
2020
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3. Prophylactic colectomy and rectal preservation in FAP: systematic endoscopic follow-up and adenoma destruction changes natural history of polyposis

Author

Antoine Breton, Mathieu Pioche, Olivier Vinet, Jean Christophe Saurin, Nicolas Benech, Gilles Poncet, Arnaud Pasquer, and Jérôme Rivory

Subjects
medicine.medical_specialty, Original article, Adenoma, business.industry, Proctocolectomy, medicine.medical_treatment, Incidence (epidemiology), RC799-869, Diseases of the digestive system. Gastroenterology, Anastomosis, medicine.disease, Prophylactic Surgery, Familial adenomatous polyposis, Surgery, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, medicine, Fecal incontinence, 030211 gastroenterology & hepatology, Pharmacology (medical), medicine.symptom, business, Colectomy
Abstract

Background and study aims Prophylactic surgery of familial adenomatous polyposis (FAP) includes total colectomy with ileorectal anastomosis (IRA) to proctocolectomy with ileoanal anastomosis (IAA). Surgical guidelines rely on studies without systematic endoscopic follow-up and treatment. Our aim was to report our experience based on a different approach: therapeutic follow-up, comparing in this setting IRA and IAA in terms of oncological safety and quality of life. Patients and methods Between January 1965 and November 2015, all patients who underwent prophylactic surgery for FAP with therapeutic endoscopic follow-up in Lyon University hospital: systematic endoscopic treatment of adenomas, were retrospectively and prospectively (since 2011) included. Results A total of 296 patients were analyzed: 92 had proctocolectomy with IAA (31.1 %), 197 total colectomy with IRA (66.5 %), and seven abdominoperineal resections (2.4 %). Median follow-up was 17.1 years (range, 0–38.1). Incidence of secondary cancer (IR vs. IAA) was 6.1 % vs. 1.1 % (P = 0.06; 95 %CI 0.001–0.36). The 15-year cancer-free and overall survival (IR vs. IAA) were 99.5 % vs 100 % (P = 0.09) and 98.9 % vs. 98.8 % (P = 0.82), respectively. Postoperative morbidity occurred in 44 patients: 29 (14.7 %) in the IRA and 15 (16.3 %) in the IAA group (P = 0.72). The mean number of stools per day in the respective groups were 4.4 (2.5) vs. 5.5 (2.6) (P = 0.001). Fecal incontinence occurred in 14 patients (7.1 %) in the IRA vs. 16 (17.4 %) in the IAA group (P = 0.03). Conclusions A combination of therapeutic endoscopic treatment and extended rectal preservation appears to be a safe alternative to ileoanal J-pouch anastomosis.

Published
2021

4. Endoscopic resection of Barrett's adenocarcinoma: Intramucosal and low‐risk tumours are not associated with lymph node metastases

Author

Aurélie Charissoux, J Rivory, Maximilien Barret, Mathieu Pioche, Jean Marc O'Brien, Guillaume Perrod, Thierry Ponchon, Olivier Guillaud, Alexandre Jaouen, Gabriel Rahmi, Frédéric Prat, Nicolas Benech, Thomas Walter, Jérémie Jacques, Jean-Christophe Saurin, Romain Legros, Vincent Lepilliez, and Valérie Hervieu

Subjects
Male, Risk, medicine.medical_specialty, Esophageal Mucosa, Esophageal Neoplasms, Oesophageal adenocarcinoma, Lymph node metastasis, Adenocarcinoma, Barrett Esophagus, 03 medical and health sciences, 0302 clinical medicine, Barrett's Adenocarcinoma, Humans, Medicine, Neoplasm Invasiveness, Endoscopic resection, Lymph node, Aged, Retrospective Studies, lymph node metastasis, business.industry, fungi, Gastroenterology, food and beverages, Endoscopy, Middle Aged, Barrett's oesophagus, medicine.anatomical_structure, Oncology, histological features, Lymphatic Metastasis, Positron-Emission Tomography, 030220 oncology & carcinogenesis, submucosal invasion, oesophageal adenocarcinoma, Original Article, Female, 030211 gastroenterology & hepatology, Esophagoscopy, France, Radiology, Lymph, business, Follow-Up Studies
Abstract

Background Superficial oesophageal adenocarcinoma can be resected endoscopically, but data to define a curative endoscopic resection are scarce. Objective Our study aimed to assess the risk of lymph node metastasis depending on the depth of invasion and histological features of oesophageal adenocarcinoma. Methods We retrospectively included all patients undergoing an endoscopic resection for T1 oesophageal adenocarcinoma among seven expert centres in France in 2004–2016. Mural invasion was defined as either intramucosal or submucosal tumours; the latter were further divided into superficial submucosal (1000 mm). Absence or presence of lymphovascular invasion and/or poorly differentiated cancer (G3) defined a low‐risk or a high‐risk tumour, respectively. For submucosal tumours, invasion depth and histological features were systematically confirmed after a second dedicated histological assessment (new 2‐mm thick slices) performed by a second pathologist. Occurrence of lymph node metastasis was recorded during the follow‐up from histological or PET CT reports when an invasive procedure was not possible. Results In total, 188 superficial oesophageal adenocarcinomas were included with a median follow‐up of 34 months. No lymph node metastases occurred for intramucosal oesophageal adenocarcinomas (n = 135) even with high‐risk histological features. Among submucosal oesophageal adenocarcinomas, only tumours with lymphovascular invasion or poorly differentiated cancer or with a depth of invasion >1000 μm developed lymph node metastasis tumours (n = 10/53%; 18.9%; hazard ratio 12.04). No metastatic evolution occurred under a 1000‐mm threshold for all low‐risk tumours (0/25), nor under 1200 mm (0/1) and three over this threshold (3/13%, 23.1%). Conclusion Intramucosal and low‐risk tumours with shallow submucosal invasion up to 1200 mm were not associated with lymph node metastasis during follow‐up. In case of high‐risk features and/or deep submucosal invasion, endoscopic resections are not sufficient to eliminate the risk of lymph node metastasis, and surgical oesophagectomy should be carried out. These results must be confirmed by larger prospective series., Key Summary Superficial oesophageal adenocarcinoma (OAC) can be resected endoscopically.Data to define a curative endoscopic resection with a low lymph node metastasis (LNM) risk are scarce especially for tumours invading the submucosa.Curative endoscopic resections have been reported in selected OAC invading the first 500 mm of the submucosa, but surgical series showed an LNM risk ranging from 0% to 50%, making endoscopic resection a questionable curative treatment.High‐risk histological features were not associated with LNM in intramucosal tumours.LNM occurred only for tumours invading the submucosa with a depth ≥1200 mm or with high‐risk histological features regardless of the depth of invasion.Endoscopic resection may be a valid and curative therapeutic option for all intramucosal tumours and for submucosal oesophageal adenocarcinoma with an invasion depth ≤1000 mm and low‐risk histological features.

Published
2021

5. Intraoperative random biopsies of strictureplasty sites can detect early small-bowel adenocarcinoma in patients with Crohn's disease

Author

Chloé Martineau, Jérémie H. Lefèvre, Najim Chafai, Lauren O'Connell, Magali Svrcek, Laurent Beaugerie, Lionel Arrive, Nicolas Benech, Anne Bourrier, Marine Camus, Edouard Chambenois, Ulriikka Chaput, Clotilde Debove, Xavier Dray, Jean-François Flejou, Nadia Hoyeau, Julien Kirchgesner, Cécilia Landman, Romain Leenhardt, Jérémie H. Lefevre, Philippe Marteau, Isabelle Nion-Larmurier, Yann Parc, Philippe Seksik, Laura Sirmai, Harry Sokol, and Dominique Wendum

Subjects
medicine.medical_specialty, Crohn's disease, Hepatology, business.industry, medicine.medical_treatment, Gastroenterology, MEDLINE, Small bowel adenocarcinoma, medicine.disease, Internal medicine, Strictureplasty, Medicine, In patient, business
Published
2021

6. Feasibility Study to Assess the Impact of a Lifestyle Intervention during Colorectal Cancer Screening in France

Author

Nathalie Kliemann, Béatrice Fervers, Marc J. Gunter, Anne Cattey-Javouhey, Tracy Lignini, Nicolas Benech, Jean-Christophe Saurin, Julien Carretier, Inge Huybrechts, Aurélia Maire, and Olivia Pérol

Subjects
Male, medicine.medical_specialty, Health Behavior, Colonoscopy, Health Promotion, colorectal cancer screening, Article, Risk Factors, Intervention (counseling), Lifestyle intervention, medicine, hospital setting, Humans, TX341-641, Healthy Lifestyle, Early Detection of Cancer, Aged, Nutrition and Dietetics, Cancer prevention, medicine.diagnostic_test, Nutrition. Foods and food supply, business.industry, Cancer, lifestyle intervention, Focus Groups, Middle Aged, Patient Acceptance of Health Care, medicine.disease, Focus group, Colorectal cancer screening, Family medicine, Feasibility Studies, Female, France, business, Colorectal Neoplasms, Logbook, Risk Reduction Behavior, Food Science, Program Evaluation, feasibility
Abstract

Current evidence suggests that 30–50% of cancers are attributable to established lifestyle risk factors. Cancer-screening has been identified as an opportunity for delivering advice on lifestyle behaviour change for cancer prevention. This study aimed to evaluate the feasibility and acceptance of promoting advice on the latest evidence-based lifestyle recommendations for cancer prevention at the time of colorectal cancer screening at two hospitals in Lyon, France. This feasibility study included 49 patients (20 men and 29 women) who were invited for colonoscopy. Patients received a leaflet with lifestyle recommendations for cancer prevention, accompanied with a logbook to plan and monitor their behavioural changes. Feedback from patients, hospital staff, and researchers was received via evaluation questionnaires (n = 26) completed after testing the educational material for at least two weeks and via two focus group discussions (n = 7 and n = 9 respectively) organized at the end of the study. All interviewed patients were interested in lowering their cancer risk, and the majority felt ready to change their lifestyle (88%), although most did not know how to decrease their risk of cancer (61%). All patients found the educational material easy to understand and sufficiently attractive and 50% of the patients reported having achieved at least one of the healthy behaviours recommended within the two weeks following the intervention. All hospital staff and almost all patients (92%) involved found that the screening program and the visits planned for colonoscopy was an appropriate moment to provide them with the educational material. This feasibility study has shown that the content, paper-based format, and time of delivery of the intervention were adequate. Health professionals seem to be willing to provide lifestyle recommendations, and patients appear interested in receiving advice for lowering their cancer risk during screening visits.

Published
2021
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7. Colon capsule endoscopy in clinical practice: lessons from a national 5-year observational prospective cohort

Author

Elia Samaha, Xavier Dray, Sylvie Sacher-Huvelin, Jean-Louis Gaudin, Nicolas Benech, Thierry Ponchon, Olivier Vinet, Jean-Christophe Saurin, Jean-Paul Galmiche, and Robert Benamouzig

Subjects
Original article, medicine.medical_specialty, Adenoma, medicine.diagnostic_test, business.industry, Colorectal cancer, General surgery, Colonoscopy, RC799-869, Diseases of the digestive system. Gastroenterology, medicine.disease, law.invention, Capsule endoscopy, law, Dysplasia, Medicine, Pharmacology (medical), Observational study, business, Prospective cohort study, Contraindication
Abstract

Background and study aims Colon capsule endoscopy (CCE) has been proposed as an alternative to colonoscopy for screening patients at average risk of colorectal cancer (CRC). A prospective national cohort was developed to assess relevance of CCE in real-life practice and its short- and long-term impacts on clinical management. Patients and methods All patients who underwent a CCE in France were prospectively enrolled from January 2011 to May 2016 and reached annually by phone until May 2017. All CCE and colonoscopy reports were systematically collected. Results During the study period, 689 CCEs were analyzed from 14 medical centers. Median follow-up time was 35 months [IQR: 12–50]. Indication for CCE was mainly for elderly patients (median age: 70 years, IQR: [61–79]) due to anesthetic or colonoscopy contraindication (n = 307; 44.6 %). Only 337 CCEs (48.9 %) were both complete and with adequate bowel preparation. Advanced neoplasia (adenoma with high-grade dysplasia or CRC) was diagnosed following 32 CCEs (4.6 %). Among patients who underwent colonoscopy or therapeutic surgery following CCE, 18.8 % of all advanced neoplasias (6/32) had not been diagnosed by CCE mainly due to technical issues. Performing a colonoscopy in the case of significant polyps or insufficient bowel cleansing or after an incomplete CCE allowed the diagnosis of 96.9 % of all identified advanced neoplasias (31/32). Conclusions Outside the scope of academic trials, improvement is needed to increase the reliability of CCE as less than half were considered optimal i. e. complete with adequate bowel cleansing. Most of missed colonic advanced neoplasia were due to incomplete CCE with distal neoplasia location.

Published
2021

8. Parameters influencing the pharmacokinetics/pharmacodynamics of piperacillin/tazobactam in patients with febrile neutropenia and haematological malignancy: a prospective study

Author

Nicolas, Benech, Oana, Dumitrescu, Anne, Conrad, Marie, Balsat, Etienne, Paubelle, Sophie, Ducastelle-Lepretre, Hélène, Labussière-Wallet, Gilles, Salles, Sabine, Cohen, Sylvain, Goutelle, Florence, Ader, and M, Wallon

Subjects
Adult, Male, 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Population, Microbial Sensitivity Tests, Neutropenia, 030226 pharmacology & pharmacy, Tazobactam, Gastroenterology, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Internal medicine, polycyclic compounds, medicine, Humans, Pharmacology (medical), Infusions, Intravenous, education, Aged, Febrile Neutropenia, Pharmacology, education.field_of_study, Dose-Response Relationship, Drug, business.industry, Middle Aged, medicine.disease, Anti-Bacterial Agents, Piperacillin, Tazobactam Drug Combination, Treatment Outcome, Infectious Diseases, Hematologic Neoplasms, Pharmacodynamics, Piperacillin/tazobactam, Female, Drug Monitoring, business, Biomarkers, Febrile neutropenia, medicine.drug, Piperacillin
Abstract

Objectives To assess population pharmacokinetics (PK) and pharmacodynamics (PD) of both piperacillin and tazobactam in neutropenia patients and examine dosage requirements related to the MIC distribution for Gram-negative bacteria involved in bloodstream infections (BSIs). Methods We conducted a prospective study including adult haematological malignancy patients with febrile neutropenia receiving piperacillin/tazobactam as short (30 min) or prolonged (4 h) intravenous infusions. Concentration data were analysed using a population approach. Dosing simulations with the final model investigated factors influencing the PK/PD of piperacillin/tazobactam quantified by fT>MIC or PTA for piperacillin and tazobactam, respectively. In parallel, the local MIC distribution of β-lactams was documented for Gram-negative bacteria involved in BSIs. Results Over 10 months, 31 patients were enrolled, with 11 (35.5%) short and 20 (64.5%) prolonged infusion regimens. A one-compartment model adequately described the data for both drugs. Prolonged infusion, increased serum alkaline phosphatase (ALP) values and renal function impairment were associated with increased piperacillin fT>MIC. For patients with normal or augmented renal CL, dosing regimens q8h or q6h with 30 min of infusion were insufficient to achieve acceptable PTA for piperacillin/tazobactam at the median MIC value of 8 mg/L. Prolonged infusion of large doses was associated with the best PTA for both piperacillin and tazobactam. Conclusions In a population of haematological malignancy patients with neutropenia, renal function and ALP influenced the PK of piperacillin/tazobactam. Prolonged intravenous infusion would optimize the PK of piperacillin/tazobactam, especially in the case of augmented renal CL and/or low-range bacterial susceptibility.

Published
2019

9. Management of small bowel polyps

Author

Jean Christophe Saurin, Nicolas Benech, and Mathieu Pioche

Subjects
Adenoma, Enteroscopy, medicine.medical_specialty, Balloon Enteroscopy, Hamartoma, Peutz-Jeghers Syndrome, Disease, Diagnostic tools, Capsule Endoscopy, law.invention, 03 medical and health sciences, 0302 clinical medicine, Capsule endoscopy, law, X ray computed, Intestinal Neoplasms, Intestine, Small, Humans, Medicine, business.industry, General surgery, Gastroenterology, Disease Management, Intestinal Polyps, Colorectal Neoplasms, Hereditary Nonpolyposis, Magnetic Resonance Imaging, digestive system diseases, Adenomatous Polyposis Coli, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Small Bowel Polyp, Treatment decision making, Tomography, X-Ray Computed, business
Abstract

Purpose of review Benign small bowel polyps or mass are clinically poorly distinguishable from malignant small bowel masses, and the diagnostic conditions are almost the same. The important point for clinicians is first to take advantage of the different available diagnostic tools to optimize the diagnostic algorithm of a small bowel polyp or mass. Next, according to the clinical situation, associated disease or sporadic situation, the difficulty is to adapt the treatment decision to the patient situation. Recent findings The last 20 years have been marked by the development of major diagnostic tools for small bowel diseases (capsule endoscopy, cross-sectional imaging with enteroclysis and balloon-assisted enteroscopy) and by the major decrease of intra-operative enteroscopy as a diagnostic mean. Summary On the basis of considerable development of capsule endoscopy and the improvement of cross-sectional small bowel imagining, small bowel polyps represent now a frequent clinical situation for gastroenterologists.

Published
2019

10. Fourteen-day survival among older adults with severe infection with severe acute respiratory syndrome coronavirus 2 treated with corticosteroid: a cohort study

Author

Laure Gallay, Viet-Thi Tran, Elodie Perrodeau, Nicolas Vignier, Matthieu Mahevas, Francesca Bisio, Emmanuel Forestier, Francois-Xavier Lescure, François-Xavier Lescure, Thibaut Fraisse, Diane Sanderink, Bertrand Lioger, Camille Boutrou, Anne - Laure Destrem, Pascal Gicquel, Martin Martinot, Jérémie Pasquier, Jean Reuter, Helene Desmurs-Clavel, Nicolas Benech, Boris Bienvenu, Guillemette Frémont, François Goehringer, Guillaume Chapelet, Olivier Grossi, Didier Laureillard, Cyrille Gourjault, Alexandre Lahens, Célia Azoulay, Nicolas Carlier, Gianpiero Tebano, Jérôme Pacanowski, Simone Tunesi, Nadège Lemaire, Laurent Bellec, Firouze Bani-Sadr, Marie Pichenot, Kevin Alexandre, Laurie Masse, Olivier Robineau, Camille Thorey, Sophie Deriaz, Julien Saison, Marie Gousseff, Laura Goehrs, Fanny Pommeret, and Université de Paris, Centre de Recherche Epidémiologie et Statistiques (CRESS UMR 1153) (CRESS UMR 1153)

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, medicine.drug_class, [SDV]Life Sciences [q-bio], 030106 microbiology, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Prednisone, Internal medicine, medicine, 030212 general & internal medicine, Adverse effect, ComputingMilieux_MISCELLANEOUS, business.industry, Hazard ratio, General Medicine, medicine.disease, 3. Good health, Pneumonia, Infectious Diseases, Relative risk, Corticosteroid, business, medicine.drug, Cohort study
Abstract

Objective To assess the effectiveness of corticosteroids among older adults with coronavirus disease 2019 (COVID-19) pneumonia requiring oxygen. Methods We used routine care data from 36 hospitals in France and Luxembourg to assess the effectiveness of corticosteroids with at least 0.4 mg/kg/day equivalent prednisone (treatment group) versus standard of care (control group). Participants were adults aged 80 years or older with PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or CT scan images typical of COVID-19 pneumonia, requiring oxygen ≥3 L/min, and with an inflammatory syndrome (C-reactive protein ≥40 mg/L). The primary outcome was overall survival at day 14. In our main analysis, characteristics of patients at baseline (i.e. time when patients met all inclusion criteria) were balanced by using propensity-score inverse probability of treatment weighting. Results Among the 267 patients included in the analysis, 98 were assigned to the treatment group. Their median age was 86 years (interquartile range 83–90 years) and 95% had a SARS-CoV-2 PCR-confirmed diagnosis. In total, 43/98 (43.9%) patients in the treatment group and 84/166 (50.6%) in the control group died before day 14 (weighted hazard ratio 0.67, 95% CI 0.46–0.99). The treatment and control groups did not differ significantly for the proportion of patients discharged to home/rehabilitation at day 14 (weighted relative risk 1.12, 95% CI 0.68–1.82). Twenty-two (16.7%) patients receiving corticosteroids developed adverse events, but only 11 (6.4%) from the control group. Conclusions Corticosteroids were associated with a significant increase in the overall survival at day 14 of patients aged 80 years and older hospitalized for severe COVID-19.

Published
2021

11. Impact on the Gut Microbiota of Intensive and Prolonged Antimicrobial Therapy in Patients With Bone and Joint Infection

Author

Benoît Levast, Nicolas Benech, Cyrielle Gasc, Cécile Batailler, Eric Senneville, Sébastien Lustig, Cécile Pouderoux, David Boutoille, Lilia Boucinha, Frederic-Antoine Dauchy, Valérie Zeller, Marianne Maynard, Charles Cazanave, Thanh-Thuy Le Thi, Jérôme Josse, Joël Doré, Frederic Laurent, Tristan Ferry, MaaT Pharma [Lyon], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL), Service de Chirurgie Orthopédique [Centre Albert Trillat], Centre Albert Trillat [Hôpital de la Croix-Rousse - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Université de Lille, Service Régional Universitaire des Maladies Infectieuses et du Voyageur, Centre Hospitalier de Tourcoing, Université de Nantes (UN), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), USC EA 3671, infections humaines à mycoplasmes et chlamydiae, Université de Bordeaux (UB)-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), 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), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), This study was funded by MaaT Pharma (http://www.maatpharma.com) as part of the Concours Mondial de l'Innovation funded by Banque Publique d'Investissement-France., Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and 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)

Subjects
0301 basic medicine, medicine.medical_specialty, Bone and joint infection, medicine.drug_class, 030106 microbiology, Antibiotics, Gut microbiota, Gut flora, Gastroenterology, Antimicrobial therapy, 03 medical and health sciences, chemistry.chemical_compound, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, medicine, Microbiome, Prospective cohort study, Feces, Original Research, lcsh:R5-920, biology, business.industry, Neopterin, General Medicine, biology.organism_classification, Antimicrobial, medicine.disease, 3. Good health, 030104 developmental biology, chemistry, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Medicine, Dysbiosis, business, lcsh:Medicine (General)
Abstract

There is a growing interest in the potentially deleterious impact of antibiotics on gut microbiota. Patients with bone and joint infection (BJI) require prolonged treatment that may impact significantly the gut microbiota. We collected samples from patients with BJI at baseline, end of antibiotics (EOT), and 2 weeks after antibiotic withdrawal (follow-up, FU) in a multicenter prospective cohort in France. Microbiota composition was determined by shotgun metagenomic sequencing. Fecal markers of gut permeability and inflammation as well as multi-drug-resistant bacteria (MDRB) and Clostridioides difficile carriage were assessed at each time point. Sixty-two patients were enrolled: 27 native BJI, 14 osteosynthesis-related BJI, and 21 prosthetic joint infections (PJI). At EOT, there was a significant loss of alpha-diversity that recovered at FU in patients with native BJI and PJI, but not in patients with osteosynthesis-related BJI. At EOT, we observed an increase of Proteobacteria and Bacteroidetes that partially recovered at FU. The principal component analysis (PCoA) of the Bray–Curtis distance showed a significant change of the gut microbiota at the end of treatment compared to baseline that only partially recover at FU. Microbiota composition at FU does not differ significantly at the genus level when comparing patients treated for 6 weeks vs. those treated for 12 weeks. The use of fluoroquinolones was not associated with a lower Shannon index at the end of treatment; however, the PCoA of the Bray–Curtis distance showed a significant change at EOT, compared to baseline, that fully recovered at FU. Levels of fecal neopterin were negatively correlated with the Shannon index along with the follow-up (r2 = 0.17; p < 0.0001). The PCoA analysis of the Bray–Curtis distance shows that patients with an elevated plasma level of C-reactive protein (≥5 mg/L) at EOT had a distinct gut microbial composition compared to others. MDRB and C. difficile acquisition at EOT and FU represented 20% (7/35) and 37.1% (13/35) of all MDRB/C. difficile-free patients at the beginning of the study, respectively. In patients with BJI, antibiotics altered the gut microbiota diversity and composition with only partial recovery, mucosal inflammation, and permeability and acquisition of MDRB carriage. Microbiome interventions should be explored in patients with BJI to address these issues.

Published
2021

12. Tryptophan metabolites get the gut moving

Author

Nathalie Rolhion, Harry Sokol, Nicolas Benech, 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 Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), and Sokol, Harry

Subjects
[SDV]Life Sciences [q-bio], Cell, Enteroendocrine cell, Microbiology, 03 medical and health sciences, 0302 clinical medicine, Virology, medicine, Receptor, 030304 developmental biology, 0303 health sciences, biology, fungi, digestive, oral, and skin physiology, Tryptophan, food and beverages, biology.organism_classification, Neuronal activation, Intestinal motility, Cell biology, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Parasitology, Enteric nervous system, 030217 neurology & neurosurgery, Bacteria
Abstract

International audience; How gut microbes can regulate the enteric nervous system and gut-brain communications is a field of intense research. In this issue of Cell Host & Microbe, Ye et al. demonstrate that bacteria can control intestinal motility and vagal neuronal activation via tryptophan catabolites through the receptor TrpA1 of enteroendocrine cells.

Published
2021

13. Expert centres for faecal microbiota transplantation: The guarantee for safe and effective use of faecal transplants

Author

Nicolas Benech, Harry Sokol, Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), French Group of Fecal Microbiota Transplantation [Paris] (GFTF), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, 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), 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), Paris Center for Microbiome Medicine, HAL-SU, Gestionnaire, Centre de Recherche Saint-Antoine (CRSA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)

Subjects
medicine.medical_specialty, Blastocystis sp, MEDLINE, donor screening, Faecal microbiota transplantation, Luminal, Feces, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, Humans, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Blastocystis, biology, business.industry, Clostridioides difficile, Gastrointestinal Microbiome, Gastroenterology, fecal microbiota transplantation, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Fecal bacteriotherapy, biology.organism_classification, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Major Articles and Commentaries, Treatment Outcome, AcademicSubjects/MED00290, Oncology, Clostridium Infections, 030211 gastroenterology & hepatology, CDI, business
Abstract

Background Patients with multiple recurrent Clostridioides difficile infections (rCDI) are treated with fecal microbiota transplantation (FMT), using feces provided by healthy donors. Blastocystis colonization of donors is considered an exclusion criterion, whereas its pathogenicity is still under debate. Methods The introduction of molecular screening for Blastocystis sp. at our stool bank identified 2 donors with prior negative microscopies but positive polymerase chain reactions (PCRs). Potential transmission of Blastocystis sp. to patients was assessed on 16 fecal patient samples, pre- and post-FMT, by PCR and subtype (ST) analyses. In addition, clinical outcomes for the treatment of rCDI (n = 31), as well as the development of gastrointestinal symptoms, were assessed. Results There was 1 donor who carried Blastocystis ST1, and the other contained ST3. All patients tested negative for Blastocystis prior to FMT. With a median diagnosis at 20.5 days after FMT, 8 of 16 (50%) patients developed intestinal colonization with Blastocystis, with identical ST sequences as their respective donors. Blastocystis-containing fecal suspensions were used to treat 31 rCDI patients, with an FMT success rate of 84%. This success rate was not statistically different from patients transferred with Blastocystis sp.–negative donor feces (93%, 76/82). Patients transferred with Blastocystis sp.–positive donor feces did not report any significant differences in bowel complaints in the first week, after 3 weeks, or in the months following FMT. Conclusions We demonstrated the first transmission of Blastocystis ST1 and ST3 from donors to patients by FMT. This did not result in gastrointestinal symptomatology or have any significant effect on rCDI treatment outcomes., Transmission of Blastocystis by fecal microbiota transplantation (FMT) from colonized donors occurred in 50% of patients. Transfer did not result in development of gastrointestinal symptoms or affect the outcome of the FMT treatment in patients with recurrent Clostridioides difficile infections.

Published
2020

14. Clinical recurrences of COVID-19 symptoms after recovery: Viral relapse, reinfection or inflammatory rebound?

Author

Anne Conrad, Benjamin Wyplosz, Nicolas Benech, Matthieu Mahévas, Bruno Pozzetto, Adrien Lemaignen, Laure Gallay, Dominique Batisse, Rocco Collarino, Dorsaf Slama, Cédric Joseph, Nicolas Vignier, François Goehringer, Elisabeth Botelho-Nevers, Marie Gousseff, Bruno Levy, Pauline Penot, Dominique Salmon, François-Xavier Lescure, Kevin Bouiller, Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Centre Hospitalier Intercommunal André Grégoire [Montreuil] (CHI André Gregoire), Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'immunologie [HEGP, Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Maladies Infectieuses et Tropicales [CHU Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service Maladies infectieuses et tropicales [AP-HP Hôpital Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pathologies infectieuses et tropicales [CHU Amiens], CHU Amiens-Picardie, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Service de Médecine Interne et Maladies Infectieuses [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Soins Intensifs [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Henri Mondor [Créteil], Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet - Saint-Étienne (UJM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, CHU Henri Mondor, Université Jean Monnet [Saint-Étienne] (UJM), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, MESH: Coronavirus Infections, Disease, 0302 clinical medicine, MESH: Aged, 80 and over, Recurrence, MESH: Reverse Transcriptase Polymerase Chain Reaction, Pandemic, MESH: COVID-19, 030212 general & internal medicine, Young adult, MESH: Aged, MESH: Middle Aged, MESH: Follow-Up Studies, 3. Good health, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Young Adult, MESH: RNA, Viral, MESH: Betacoronavirus, Microbiology (medical), medicine.medical_specialty, MESH: Pandemics, Coronavirus disease 2019 (COVID-19), 030106 microbiology, Article, Viral Relapse, 03 medical and health sciences, Internal medicine, medicine, Humans, MESH: SARS-CoV-2, Qatar, MESH: Humans, SARS-CoV-2, business.industry, COVID-19, Retrospective cohort study, MESH: Adult, MESH: Retrospective Studies, medicine.disease, MESH: Male, MESH: Recurrence, Pneumonia, MESH: Pneumonia, Viral, Reinfection, Epidemiologic data, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; For the first 3 months of COVID-19 pandemic, COVID-19 was expected to be an immunizing non-relapsing disease. We report a national case series of 11 virologically-confirmed COVID-19 patients having experienced a second clinically- and virologically-confirmed acute COVID-19 episode. According to the clinical history, we discuss either re-infection or reactivation hypothesis. Larger studies including further virological, immunological and epidemiologic data are needed to understand the mechanisms of these recurrences.

Published
2020

15. Septic shock due to refractory severe clostridioides difficile colitis rapidly resolving after faecal microbiota transplantation

Author

Nicolas Benech, Céline Monard, Tristan Ferry, and Gilles Leboucher

Subjects
0301 basic medicine, medicine.medical_specialty, Images In…, medicine.medical_treatment, 030105 genetics & heredity, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Intensive care, Diabetes mellitus, Internal medicine, Medicine, Humans, Medical history, Colitis, Dialysis, Enterocolitis, Pseudomembranous, Aged, 80 and over, business.industry, Septic shock, Clostridioides difficile, General Medicine, Fecal Microbiota Transplantation, medicine.disease, Intensive care unit, Shock, Septic, Female, business, 030217 neurology & neurosurgery, Kidney disease
Abstract

An 80-year-old woman presented with septic shock and severe colitis at the intensive care unit. Her main personal medical history consisted of obesity, diabetes mellitus, high blood pressure and end-stage chronic kidney disease requiring dialysis. She was previously admitted to another hospital for

Published
2020

16. Fecal microbiota transplantation in gastrointestinal disorders: time for precision medicine

Author

Harry Sokol and Nicolas Benech

Subjects
0301 basic medicine, lcsh:QH426-470, Gastrointestinal Diseases, lcsh:Medicine, Inflammatory bowel diseases, Bioinformatics, law.invention, Fecal microbiota transplantation, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Genetics, medicine, Humans, Molecular Biology, Genetics (clinical), Irritable bowel syndrome, business.industry, Comment, Precision medicine, lcsh:R, Inflammatory Bowel Diseases, Fecal bacteriotherapy, medicine.disease, Human genetics, lcsh:Genetics, 030104 developmental biology, Molecular Medicine, 030211 gastroenterology & hepatology, business
Abstract

Fecal microbiota transplantation (FMT) has demonstrated efficacy in treating inflammatory bowel diseases and irritable bowel syndrome in an increasing number of randomized controlled trials. Recently published data gives striking insights into the factors associated with FMT success paving the road for the use of precision medicine in gastrointestinal disorders.

Published
2020

17. Endoscopic resection of early-stage SMAD4 juvenile polyposis does not prevent disease spreading in the stomach

Author

Pierre-Marie Lavrut, Jérôme Rivory, Jean-Christophe Saurin, Laura Calavas, Mathieu Pioche, Etienne Baldysiak, and Nicolas Benech

Subjects
medicine.medical_specialty, Intestinal Polyposis, business.industry, Stomach, Gastroenterology, Juvenile Polyposis, Surgery, medicine.anatomical_structure, Neoplastic Syndromes, Hereditary, Disease spreading, Humans, Medicine, Endoscopic resection, Stage (cooking), business, Smad4 Protein
Published
2019

18. Load sharing between synergistic muscles characterized by a ligand-binding approach and elastography

Author

Gustavo A. Grinspan, Liliam Fernandes de Oliveira, Maria Clara Brandao, Andrés Pomi, and Nicolás Benech

Subjects
Medicine, Science
Abstract

Abstract The skeletal muscle contraction is determined by cross-bridge formation between the myosin heads and the actin active sites. When the muscle contracts, it shortens, increasing its longitudinal shear elastic modulus ( $${\mu }_{L}$$ μ L ). Structurally, skeletal muscle can be considered analogous to the molecular receptors that form receptor–ligand complexes and exhibit specific ligand-binding dynamics. In this context, this work aims to apply elastography and the ligand-binding framework to approach the possible intrinsic mechanisms behind muscle synergism. Based on the short-range stiffness principle and the acoustic–elasticity theory, we define the coefficient $$C$$ C , which is directly related to the fraction saturation of molecular receptors and links the relative longitudinal deformation of the muscle to its $${\mu }_{L}$$ μ L . We show that such a coefficient can be obtained directly from $${\mu }_{L}$$ μ L estimates, thus calculating it for the biceps brachii, brachioradialis, and brachialis muscles during isometric elbow flexion torque (τ) ramps. The resulting $$C\left(\tau \right)$$ C τ curves were analyzed by conventional characterization methods of receptor–ligand systems to study the dynamical behavior of each muscle. The results showed that, depending on muscle, $$C\left(\tau \right)$$ C τ exhibits typical ligand-binding dynamics during joint torque production. Therefore, the above indicates that these different behaviors describe the longitudinal shortening pattern of each muscle during load sharing. As a plausible interpretation, we suggested that this could be related to the binding kinetics of the cross-bridges during their synergistic action as torque increases. Likewise, it shows that elastography could be useful to assess contractile processes at different scales related to the change in the mechanical properties of skeletal muscle.

Published
2023
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20. Back-to-Back Comparison of Colonoscopy With Virtual Chromoendoscopy Using a Third-Generation Narrow-Band Imaging System to Chromoendoscopy With Indigo Carmine in Patients With Lynch Syndrome

Author

Jerôme Bellanger, Helena Pereira, Marion Dhooge, Xavier Dray, Elia Samaha, Chrystelle Colas, JP Barbieux, Christophe Cellier, Stanislas Chaussade, Marc Le Rhun, Gabriel Rahmi, Thierry Lecomte, Camille Savale, Jean-Christophe Saurin, Gilles Chatellier, Emmanuel Coron, Guillaume Perrod, and Nicolas Benech

Subjects
Adenoma, Adult, Male, medicine.medical_specialty, Time Factors, Adolescent, Colon, Colonoscopy, Color, Indigo Carmine, Chromoendoscopy, 03 medical and health sciences, chemistry.chemical_compound, Narrow Band Imaging, Young Adult, 0302 clinical medicine, medicine, Humans, In patient, Prospective Studies, Intestinal Mucosa, Coloring Agents, Aged, Aged, 80 and over, Narrow-band imaging, Hepatology, medicine.diagnostic_test, business.industry, Gastroenterology, Middle Aged, medicine.disease, Colorectal Neoplasms, Hereditary Nonpolyposis, digestive system diseases, Lynch syndrome, Third generation, Clinical Practice, Indigo carmine, chemistry, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Radiology, business, Colonography, Computed Tomographic
Abstract

Colonoscopic screening with indigo carmine chromoendoscopy (ICC) in patients with Lynch syndrome (LS) improves the adenoma detection rate but is time consuming and poorly used in clinical practice. Narrow-band imaging (NBI), a virtual chromoendoscopy technique, highlights superficial mucosal vessels and improves adenoma characterization. We conducted a prospective multicenter trial in a back-to-back fashion to compare the third-generation NBI with ICC for detecting colonic adenomas in patients with LS.In a multicenter, prospective, noninferiority trial, 138 patients underwent a double colonoscopy, first with NBI, followed by ICC, in a back-to-back design. The primary noninferiority outcome measure was the number of patients with at least one adenoma after NBI compared with the number of patients with at least one adenoma after NBI and ICC.The 138 analyzable patients were all proven mismatch repair mutation carriers for LS (MLH1 = 33%, MSH2 = 47%, MSH6 = 15%, PMS2 = 4%, and EPCAM = 1%). The mean age (SD) was 40.5 (14.7) years, and 64 (46.4%) were men. The median withdrawal time for an NBI procedure was 8 minutes (interquartile range 6-11) compared with 13 minutes (interquartile range 8-17) for ICC. At least one adenoma was detected during the initial NBI pass in 28 patients (20.3%), and 42 patients (30.4%) had at least one adenoma detected after both NBI and ICC (difference, 10.1%; 95% confidence interval, -0.1%-20.3%); this represents an increase of 50.0% of the adenoma detection rate. ICC detected additional adenomas in 25 patients (18.1%).Colonoscopy combining NBI and ICC detects more adenomas than third-generation NBI alone in patients with LS, respectively, 30.4% vs 20.3% (difference, 10.1%; 95% confidence interval, -0.1 to 20.3), thus failing the noninferiority assumption of NBI compared with combined NBI and ICC. Although less time consuming, colonoscopy using the third-generation NBI cannot be recommended to replace ICC in patients with LS.

Published
2019

21. Fecal Microbiota Transplantation for Ulcerative Colitis

Author

Harry Sokol, Nicolas Benech, and Nathalie Kapel

Subjects
medicine.medical_specialty, business.industry, Gastrointestinal Microbiome, General Medicine, Fecal bacteriotherapy, Fecal Microbiota Transplantation, medicine.disease, Gastroenterology, Ulcerative colitis, Feces, Internal medicine, Medicine, Humans, Colitis, Ulcerative, Colitis, business
Published
2019

22. Why not simply treat large adenomas of the rectum and ileal pouch after colectomy in familial adenomatous polyposis?

Author

Nicolas Benech, Arnaud Pasquer, Laura Calavas, and Jean-Christophe Saurin

Subjects
medicine.medical_specialty, business.industry, medicine.medical_treatment, Rectum, medicine.disease, Gastroenterology, Familial adenomatous polyposis, medicine.anatomical_structure, Editorial, Internal medicine, medicine, Pharmacology (medical), lcsh:Diseases of the digestive system. Gastroenterology, Pouch, lcsh:RC799-869, business, Colectomy
Published
2019

23. Multicenter Evaluation of Clinical Efficacy and Safety of Per-Oral Endoscopic Myotomy in Children

Author

Lybil B. Mendoza Alvarez, Yuto Shimamura, Eduardo Albéniz, Jérôme Rivory, Adrien Choné, Maximilien Barret, Pankaj N. Desai, Hinorari Shiwaku, Alain Lachaux, François Mion, Nikos Eleftheriadis, Nicolas Benech, Gabriel Arevalo, Stefan Seewald, Mathew Abraham, Mouen A. Khashab, Jeffrey M. Marks, Kanefumi Yamashita, Peter V. Draganov, Mathieu Pioche, Marcel Tantau, Sabine Roman, Burkhard H.A. von Rahden, Rémi Dubois, Stanislas Chaussade, Pietro Familiari, Haruhiro Inoue, Fabien Subtil, Thierry Ponchon, IIS, The University of Tokyo (UTokyo), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Stanford University, Institut des Nanosciences de Paris (INSP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Département de pédiatrie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Application des ultrasons à la thérapie (LabTAU), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Institut des Sciences de la Terre (ISTerre), Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Institut national des sciences de l'Univers (INSU - CNRS)-Institut de recherche pour le développement [IRD] : UR219-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM), The University of Tokyo, Stanford University [Stanford], Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), and Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-PRES Université de Grenoble-Institut de recherche pour le développement [IRD] : UR219-Institut national des sciences de l'Univers (INSU - CNRS)-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Université Joseph Fourier - Grenoble 1 (UJF)

Subjects
Male, Natural Orifice Endoscopic Surgery, Myotomy, Pediatrics, medicine.medical_specialty, Adolescent, Fistula, medicine.medical_treatment, Settore MED/18 - CHIRURGIA GENERALE, [SDV]Life Sciences [q-bio], Achalasia, multicenter, per-oral endoscopic myotomy, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Japan, 030225 pediatrics, medicine, Humans, endoscopy, Adverse effect, Retrospective Studies, business.industry, Gastroenterology, Reflux, Retrospective cohort study, medicine.disease, Dilatation, United States, 3. Good health, Esophageal Achalasia, Europe, achalasia, international, Pediatrics, Perinatology and Child Health, GERD, Female, 030211 gastroenterology & hepatology, medicine.symptom, business, Subcutaneous emphysema
Abstract

International audience; OBJECTIVES: Per-Oral Endoscopic Myotomy (POEM) is a recommended treatment modality for achalasia, but there is little published data for its use in children. The objective of the present study was to evaluate whether POEM is clinically effective and safe for children. METHODS: International multicenter retrospective study conducted in 14 tertiary centers that included consecutive children who underwent POEM between January 2012 and August 2018. Outcomes such as clinical response were assessed when available. Adverse events and factors associated with clinical failure were also investigated. RESULTS: A total of 117 patients (mean +/- SD age: 14.2 +/- 3.7 years) underwent POEM for achalasia (type I n=36, II n=66, III n=8). Among these, 30 (26%) were pre-treated (botulinum injection and/or pneumatic dilatation). Mean +/- SD baseline Eckardt score was 7.5 +/- 2.0. Clinical success was achieved in 90.6% of cases (95%CI [83.8%;95.2%]) in the intention-to-treat analysis. The mean +/- SD Eckardt score post-POEM was 0.9 +/- 1.2 (p\textless0.001). The mean duration of follow-up time 545 days (range: 100-1612). A total of 7 adverse events occurred (4 mucosotomies, 2 subcutaneous emphysema, 1 esopleural fistula). Gastroesophageal reflux symptoms were seen in 17 patients (15%); missing data for 10 patients (9%). There was a trend towards more frequent clinical failure in achalasia associated with genetic disorders (40% versus 8%, p=0.069). CONCLUSION: POEM in pediatric patients appears to be effective and safe, although there was a trend towards more frequent clinical failure achalasia associated with genetic disorders. Further studies are needed to assess the long-term outcomes, especially the consequences of GERD.

Published
2019

24. Desmoid Tumors and Celecoxib with Sorafenib

Author

Nicolas Benech, Thomas Walter, and Jean-Christophe Saurin

Subjects
0301 basic medicine, Sorafenib, Oncology, medicine.medical_specialty, business.industry, General Medicine, Response to treatment, Resection, body regions, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, Celecoxib, heterocyclic compounds, business, neoplasms, medicine.drug
Abstract

Desmoid tumors are difficult to treat when not amenable to resection. Two cases are reported in which there was regression of desmoid tumors in response to treatment with sorafenib and celecoxib.

Published
2017

25. Faecal microbiota transplantation in recurrent Clostridium difficile infection: Recommendations from the French Group of Faecal microbiota Transplantation

Author

Harry Sokol, Tatiana Galperine, Nathalie Kapel, Pierre Bourlioux, Philippe Seksik, Frederic Barbut, Julien Scanzi, François Chast, Rui Batista, Francisca Joly, Anne-Christine Joly, Anne Collignon, Benoit Guery, Laurent Beaugerie, Laurent Alric, Jean-Paul Aucouturier, Aurelien Amiot, Pascale Bemer, Robert Benamouzig, Nicolas Benech, Claire Billioud, Gille Boschetti, Nour Boubaddi, Guillaume Bouguen, Arnaud Bourreille, Franck Carbonnel, Elodie Cesbron-Metivier, Benoit Coffin, Michael Collins, Benjamin Davido, Thierry Davion, Aurelilen Dinh, Henri Duboc, Philippe Ducrotte, Thibaut Fraisse, Bertrand Gachot, Marielle Guillet, B. Heyman, Elodie Metivier, Frederic Mille, Alexis Mosca, Biba Nebbad, Gabriel Perlemuter, Thierry Piche, Jean-Marie Reimund, Matthieu Revest, Jean-Marc Sabate, Iradj Sobhani, Stephane Schneider, Caroline Trang, Stephanie Viennot, Maurice Viala, Cosmin Voican, Frank Zerbib, CHU Saint-Antoine [APHP], French group of faecal microbotia transplantation (FGFT), Infectious diseases department, CHRU Claude Huriez, Ecosystème intestinal, probiotiques, antibiotiques (EA 4065), Université Paris Descartes - Paris 5 (UPD5), CHU Pitié-Salpêtrière [APHP], Pharmacy academy - Paris, Microbiology department, Université Paris-Sud - Paris 11 (UP11), Gastro-enterology department, CHU Clermont-Ferrand, Clinical pharmacy department, APHP, AP-HP Hôpital Beaujon, Écosystème Microbien Digestif et Santé, Institut National de la Recherche Agronomique (INRA)-Université Paris-Sud - Paris 11 (UP11), Gastroenterology and nutrition department, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -CHU Saint-Antoine [APHP], French group of faecal microbotia transplantation ( FGFT ), Ecosystème intestinal, probiotiques, antibiotiques ( EA 4065 ), Université Paris Descartes - Paris 5 ( UPD5 ), Functional coprology laboratory, Université Paris-Sud - Paris 11 ( UP11 ), C. difficile Nationale reference laboratory, Pharmacy department, Institut National de la Recherche Agronomique ( INRA ) -Université Paris-Sud - Paris 11 ( UP11 ), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Beaujon [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
0301 basic medicine, medicine.medical_specialty, 030106 microbiology, Pharmacy, Faecal microbiota transplantation, Donor Selection, Microbiology, 03 medical and health sciences, 0302 clinical medicine, fluids and secretions, Recurrence, medicine, Humans, Intensive care medicine, faecal microbiota transplantation, Enterocolitis, Pseudomembranous, Hepatology, Clostridioides difficile, Donor selection, business.industry, Patient Selection, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Clostridium difficile, Fecal Microbiota Transplantation, 3. Good health, Clinical Practice, Clinical trial, Infectious disease (medical specialty), recommendations, Clostridium Infections, 030211 gastroenterology & hepatology, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, France, Specimen preparation, business
Abstract

International audience; Faecal microbiota transplantation is effective for treating recurrent forms of Clostridium difficile infection and its use in this indication is recommended in the most recent European and North American guidelines. In this context, faecal microbiota transplantation is beginning to be performed in France in clinical practice, while the rules governing this procedure have been defined in France only for clinical trials. To unify, secure, and evaluate practice in this field in France, the French Group of Faecal microbiota Transplantation (FGFT) was created in October 2014 with the support of the French National Society of Gastroenterology, the French Infectious Disease Society, and the National Academy of Pharmacy. We present here the deliberations of this group regarding the use of faecal microbiota transplantation for recurrent Clostridium difficile infection. The issues addressed are the indications, therapeutic sequence, delivery procedures, donor selection, methods and conditions of specimen preparation, and traceability.

Published
2016

26. Sa1900 COMPARISON OF COLONOSCOPY WITH VIRTUAL CHROMOENDOSCOPY USING THIRD GENERATION NARROW BAND IMAGING SYSTEM TO CHROMOENDOSCOPY WITH INDIGO CARMINE IN LYNCH SYNDROME PATIENTS (THE LYNCH-CHROMO STUDY)

Author

Jerôme Bellanger, Jean-Christophe Saurin, Camille Savale, Nicolas Benech, Chrystelle Colas, Stanislas Chaussade, Emmanuel Coron, Thierry Lecomte, Helena Pereira, Gabriel Rahmi, Gilles Chatellier, Marc Le Rhun, Christophe Cellier, Marion Dhooge, Elia Samaha, and Guillaume Perrod

Subjects
medicine.medical_specialty, Narrow-band imaging, medicine.diagnostic_test, business.industry, Gastroenterology, Colonoscopy, medicine.disease, Lynch syndrome, Third generation, Chromoendoscopy, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Indigo carmine, chemistry, 030220 oncology & carcinogenesis, medicine, 030211 gastroenterology & hepatology, Radiology, Nuclear Medicine and imaging, Radiology, business
Published
2018

27. Esophageal hematoma after peroral endoscopic myotomy for achalasia in a patient on antiplatelet therapy

Author

Marc O’Brien, Thierry Ponchon, François Mion, Mathieu Pioche, Jérôme Rivory, Sabine Roman, and Nicolas Benech

Subjects
Myotomy, medicine.medical_specialty, medicine.medical_treatment, Achalasia, Postoperative Hemorrhage, Esophageal Sphincter, Lower, Hematoma, Melena, medicine, Humans, Aspirin, business.industry, Gastroenterology, Diathermy, Middle Aged, medicine.disease, Dysphagia, Surgery, Esophageal Achalasia, Hemostasis, Anesthesia, Platelet aggregation inhibitor, Female, Esophagoscopy, medicine.symptom, business, Platelet Aggregation Inhibitors
Abstract

Peroral endoscopic myotomy (POEM) appears to be a successful technique for the treatment of achalasia [1]. Only a few cases of delayed bleeding have been described [2]. Here, we report a case of esophageal hematoma that developed 1 day after a patient on acetylsalicylic acid (ASA) therapy underwent POEM. A 59-year-old woman with type II achalasia was referred for a POEM procedure. She had a past history of two transient ischemic attacks, which justified continuous therapy with 75mg of ASA per day. Local hemostasis for small areas of muscular hemorrhage was performed with a diathermy forceps. The 16-cm tunnel was closed with five clips. In the following hours, the patient experienced severe epigastric pain, and the next morning, her hemoglobin level had dropped from 144 to 112g/L. She did not have any hematemesis, melena, or hemodynamic instability. A computed tomographic scan showed a large, limited hematoma measuring 34 by 110mm within the tunnel (●" Fig.1), which was closed adequately by the clips. We decided to manage this hematoma conservatively without removing the clips. At day 3, another computed tomographic scan showed a 10-mm decrease in the hematoma. The patient’s condition remained stable, and neither endoscopic hemostasis nor blood transfusion was needed. She was discharged 8 days after the procedure. Her long-term course was favorable, with total resolution of the dysphagia. The risk-to-benefit ratio of POEM depending on various conditions is not known, especially in patients on antiplatelet therapy. Delayed bleeding after POEM is a rare adverse event. To our knowledge, very few cases have been described until now (●" Table1). A conservative treatment can be considered if neither blood exteriorization nor hemodynamic instability is present. Delayed bleeding does not seem to affect the long-term efficacy of the procedure. ASA may increase the risk for bleeding and should be stopped temporarily if possible. If not, the careful preventive coagulation of visible vessels in the tunnel should be performed before it is closed.

Published
2015

29. Su1244 Accuracy of Fecal M2-Pyruvate Kinase Compared With Fecal Calprotectin to Assess Endoscopic Severity in Patients With Inflammatory Bowel Diseases

Author

Nicolas Benech, Stéphane Nancey, Jocelyne Drai, Sarah Boyer, Karine Stroeymeyt, Gilles Boschetti, Bernard Flourié, and Marion Chauvenet

Subjects
Crohn's disease, medicine.medical_specialty, Univariate analysis, Multivariate analysis, Hepatology, business.industry, Gastroenterology, bacterial infections and mycoses, medicine.disease, Ulcerative colitis, Vaccination, chemistry.chemical_compound, Mesalazine, chemistry, Internal medicine, medicine, Calprotectin, business, Feces
Abstract

CS+IS therapy (21.5% vs. 12.5%; p

Published
2015

30. Nasopharyngeal and serological anti SARS-CoV-2 IgG/IgA responses in COVID-19 patients

Author

Sylvie van der Werf, Caroline Demeret, Bernadette Crescenzo-Chaigne, Lila Bouadma, Jade Ghosn, Vincent Enouf, Sarah Tubiana, Stéphane Petres, Marie Noelle Ungeheuer, Sylvie Behillil, Nicolas Escriou, Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris], Plateforme de Microbiologie Mutualisée (PIBnet) - Mutualized Platform for Microbiology (P2M), Laboratoire d’innovation : vaccins – Innovation lab : vaccines, Plateforme technologique Production et purification de protéines recombinantes – Production and Purification of Recombinant Proteins Technological Platform (PPR), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Investigations Cliniques [CHU Bichat] (CIC plurithématique), This work was supported by the « URGENCE COVID-19 » fundraising campaign of Institut Pasteur, by REACTING (Research & Action Emerging Infectious Diseases) and by the H2020 project 101003589 (RECOVER). The French Covid Cohort is funded through the Ministry of Health and Social Affairs (PHRC n°20-0424) and Ministry of Higher Education and Research dedicated COVID19 fund., List of the membership of the French COVID cohort study group : Mélanie RORIZ, Patrick RISPAL, Sarah REDL (CHG d'Agen), Laurent LEFEBVRE, Pascal GRANIER, Laurence MAULIN (CH du Pays d'Aix, Aix en Provence), Cédric JOSEPH, Julien MOYET, Sylvie LION-DAOLIO (CHU Amiens Nord), Rafael MAHIEU, Alexandra DU-CANCELLE, Vincent DUBEE (CHU d'Angers), Stéphane SALLA-BERRY, Aldric MANUEL, Gabriel MACHEDA, Mylène MAILLET, Bruno CHANZY (CH d'Annecy Genevois), Jean-Charles GAGNARD (Hôpital privé d'Antony), Guillermo GIORDANO, Clara MOUTON PERROT, Vincent PESTRE (CH Henri Duffaut, Avignon), Cécile FICKO, Marie GOMINET, Aurore BOUSQUET (Hôpital d'instruction des armées Begin), Charline VAUCHY, Kévin BOUILLER, Maïder PAGADOY, Solène MARTY-QUINTERNET, Quentin LEPILLER (CHU Jean Minjoz, Besançon), Cyril LE BRIS, Benoit THILL, Marie-Laure CASANOVA, Georges LE FALHER, Eric OZIOL (CH de Béziers), Hugues CORDEL, Nathalie DOURNON, Olivier BOUCHAUD, Ségolène BRICHLER (Hôpital Avicenne, Bobigny), Duc NGUYEN, Pantxika BELLECAVE, Camille CICCONE, Marie-Edith LAFON (CHU Pellegrin, Bordeaux), Ségolène GREFFE (CHU Ambroise Paré, Boulogne Billancourt), Camille BOUISSE, Nicholas SEDILLOT, Damien BOUHOUR (CH Fleyriat, Bourg en Bresse), Camille CHASSIN (CH Pierre Oudot, Bourgoin-Jallieu), Erwan L'HER, Séverine ANSART, Cécile TROMEUR, Dewi GUELLEC (CHRU de Brest), Antoine MERCKX (CH de Cahors), Felix DJOSSOU (CH Andrée Rosemon, Cayenne), Vincent PEIGNE, Carola PIEROBON, Marie-Christine CARRET, Florence JEGO, Margaux ISNARD (CHMS Chambéry NH), Johann AUCHABIE, Roxane COURTOIS (CH de Cholet), Olivier LESENS (CHU Gabriel Montpied, Clermont-Ferrand), Martin MARTINOT (Hôpital Pasteur, Colmar), Olivier PICONE (Hôpital Louis Mourier, Colombes), Marie LACOSTE (CH Alpes Leman Contamine sur Arve), Brigitte ELHAR-RAR, Valérie GARRAIT, Isabelle DELACROIX, Thomas MAITRE, Jean Baptiste ASSIE (Centre Hospitalier Intercommunal de Créteil), Elsa NYAMANKOLLY (CH de Dax), François Xavier CATHERINE, Ma-thieu BLOT, Sophie MAHY, Marielle BUISSON, Lionel PIROTH, Florence GUILLOTIN, Alexis DE ROUGEMONT (CHU de Dijon Bourgogne), Valentine CAMPANA, Jérémie PASQUIER, André CABIE (CHU de Martinique, Fort de France), Simon BESSIS (Hôpital Raymond Poincaré, Garches), Olivier EPAULARD, Nicolas TERZI, Jean-François PAYEN, Laurence BOUILLET, Rebecca HAMIDFAR, Marion Le MARECHAL (CHU de Grenoble), Moïse MACHADO, Audrey BARRELET, Alexandra BEDOSSA (Grand Hôpital de l'Est Francilien site Marne-la-Vallée, Jossigny), Gwenhaël COLIN, Romain DECOURS, Thomas GUIMARD (CHD Les Oudairies, La Roche Sur Yon), Cécile GOUJARD, Stéphane JAUREGUIBERRY, Antoine CHERET (Hôpital Universitaire Bicêtre, Le Kremlin-Bicêtre), Anne Sophie RESSEGUIER (CH Emile Roux, Le Puy en Velay), Julien POISSY, Daniel MATHIEU, Saad NSEIR, Ilka ENGELMANN, Martine REMY (CHRU de Lille, Hôpital Salengro), Fanny VUOTTO, Benoit GACHET, Karine FAURE, Marielle BOYER-BESSEYRE, Kazali Enagnon (CHRU de Lille, Hôpital Fourrier), Marc LAMBERT, Arnaud SCHERPEREEL, Dominique DEPLANQUE, Stéphanie FRY, Cécile YELNIK (CHRU de Lille, Hôpital Albert Calmette), Laurent BITKER, Mehdi MEZIDI, Hodane YONIS, Nicolas BENECH, Thomas PERPOINT, Anne CONRAD, Vinca ICARD, Martine VALETTE (Hôpital de la Croix Rousse, Lyon), Simon-Djamel THIBERVILLE (Hôpital Louis Raffalli, Manosque), Stanislas REBAUDET (Hôpital Européen de Marseille), Bertrand DUSSOL (Hôpital Conception, Marseille), Sylvain DIAMANTIS, Catherine CHAKVEATZE, Clara FLATEAU (Groupe Hospitalier Sud Ile De France, hôpital de Melun), Vincent DINOT, Rostane GACI, Nadia OUAMARA (Hôpital de Mercy, CHR Metz-Thionville, Ars laquenexy), Hajnal-Gabriela ILLES, Louis GER-BAUD MORLAES, Jérôme DIMET (CH de Mont Marsan), Vincent LE MOING, Nathalie PANSU, Clément LE BIHAN, Brigitte MONTES (CHU de Montpellier), Anne Sophie BOUREAU, Clotilde ALLAVENA, Sabelline BOUCHEZ, Romain GUERY, Paul LE TURNIER, Cécile MEAR-PASSARD, Virginie FERRE (CHU de Nantes), Christophe RAPP (Hôpital Américain de Paris, Neuilly sur Seine), Elisa DE-MONCHY, Céline MICHELANGELLI, Karine RISSO (CHU de Nice), Paul LOUBET, Jean-Phillippe LAVIGNE (CHU Caremeau, Nîmes), Etienne DE MONTMOLLIN, Juliette PATRIER, Paul Henri WICKY, Lucie LE FEVRE, Pierre JACQUET, Raphael BORIE, Antoine DOSSIER, Dominique LUTON, Valentina ISERNIA, Sylvie LE GAC (Hôpital Bichat, Paris), Cécile AZOULAY, Nicolas CARLIER, Liem LUONG, Marie LACHATRE, Odile LAUNAY (Hôpital Cochin, Paris), Younes KERROUMI, Vanina MEYSSONNIER (Groupe Hospitalier Diaconesses Croix Saint-Simon, Paris), Jean-Luc DIEHL, Jean-Sébastien HULOT, Bernard CHOLLEY, Jean-Benoît ARLET, Olivier SANCHEZ (Hôpital Européen Georges Pompidou, Paris), Victoria MANDA, Laurène AZEMAR, Guylaine CASTOR-ALEXANDRE (Hôpital Lariboisière, Paris), Karine LACOMBE, Thibault CHIARABINI, Bénédicte LEFEBVRE, Laurence MORAND-JOUBERT, Djeneba FOFANA, Aurélie SCHNURIGER (Hôpital Saint Antoine, Paris), Nathalie DE CASTRO, Constance DELAUGERRE, Marie-Laure CHAIX (Hôpital Saint Louis, Paris), Julie CHAS (Hôpital Tenon, Paris), Valérie GABORIEAU, Eve LE COUSTUMIER, Walter PICARD (CH de Pau), Jean-Benoît ZABBE, Florent PEELMAN, Edouard SOUM (CH de Périgueux), Hugues AUMAÎTRE (CH de Perpignan), Elodie CURLIER, Rachida OUISSA, Isabelle FABRE (CHU de Pointe à Pitre, Guadeloupe), Blandine RAMMAERT (CHU de Poitiers), Nadia SAIDANI (CH Quimper), Firouzé BANI-SADR, Maxime HENTZIEN, Yohan N 'GUYEN, Juliette ROMARU, Kévin DIDIER (CHU Reims), Isabelle ENDERLE, Vincent THIBAULT, Fabrice LAINE, Matthieu LESOU-HAITIER, Matthieu REVEST, Pierre TATTEVIN (CHU Rennes), Jean-Christophe PLANTIER, Manuel ETIENNE, Véronique LEMEE, Eglantine FERRAND DEVOUGE, Kévin ALEXANDRE, Elise ARTAUD-MACCARI (CHU Rouen), Nathalie ALLOU, Marie LAGRANGE, Julien JABOT (CH Saint Denis et Saint Pierre, La réunion), Benoît ROZE, Delphine BREGEAUD, Younes AIT TAMLIHAT (CH Saintes), Ali HACHEMI (CH Soisson), Hélène SALVATOR, Erwan FOURN, David ZUCMAN (Hôpital Foch, Suresnes), Eric DELAVEUVE, Coline JAUD-FISCHER, Paul DUNAND (Hôpital Bel Air, Thionville), François BISSUEL (CH Thonon les Bains), Karen DELAVIGNE, Marie PIEL-JULIAN, Pierre DELOBEL, Benjamine SARTON, Marie RAFIQ, Guillaume MARTIN-BLONDEL, Laurent GUILLEMINAULT, Marlène MURRIS, Agnès SOMMET (CHU de Toulouse), Eric SENNEVILLE, Olivier ROBINEAU, Agnès MEYBECK (CH Tourcoing), Denis GAROT, Laurent PLANTIER, Valérie GISSOT, Julien MARLET, Karl STEFIC, Catherine GAUDY-GRAFFIN, Francis BARIN, Adrien LEMAIGNEN (CHU Bretonneau, Tours), Grégory CORVAISIER, Delphine LARIVIERE, Marie LANGELOT-RICHARD (CH Vannes), Elisabeth BOTELHO-NEVERS , Amandine GAGNEUX-BRUNON, Tiffany TROUILLON, Thomas BOURLET, Thomas BOURLET, Sylvie PILLET, Bruno POZZETTO (CHU de St Etienne), Antoine KIMMOUM, Bruno LEVY, Mathieu MATTEI, François GOEHRINGER, Christian RABAUD, Sibylle BEVILACQUA, Benjamin LEFEVRE, Anne GUILLAUMOT, Véronique VENARD, Hélène JEULIN, Evelyne SCHVOERER, Cédric HARTARD (CHU de Nancy, Vandoeuvre les Nancy), Pauline CARAUX PAZ, Laurent RICHIER, Mohamed EL SANHARAWI (CH Villeneuve St Georges)., European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord

Subjects
Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], Severe disease, Infectious and parasitic diseases, RC109-216, Article, Serology, 03 medical and health sciences, 0302 clinical medicine, Medicine, Mucosal Immunity, 030304 developmental biology, 0303 health sciences, biology, 030306 microbiology, business.industry, Epithelium, 3. Good health, Nucleoprotein, medicine.anatomical_structure, Antibody response, SARS CoV, 030220 oncology & carcinogenesis, Immunology, biology.protein, Antibody, business
Abstract

BackgroundThe systemic antibody responses to SARS-CoV-2 in COVID-19 patients has been extensively studied. However, much less is known about the mucosal responses in the upper airways at the site of initial SARS-CoV-2 replication. Local antibody responses in the nasopharyngeal epithelium, that are likely to determine the course of infection, have not been analysed so far nor their correlation with antibody responses in serum.MethodsThe IgG and IgA antibody responses were analysed in the plasma as well as in nasopharyngeal swabs (NPS) from the first four COVID-19 patients confirmed by RT-qPCR in France. Two were pauci-symptomatic while two developed severe disease. Taking advantage of a comprehensive series of plasma and nasopharyngeal samples, we characterized their antibody profiles from the second week post symptoms onset, by using an in-house ELISA to detect anti-SARS-CoV-2 Nucleoprotein (N) IgG and IgA.ResultsAnti-N IgG and IgA antibodies were detected in the NPS of severe patients. Overall, the levels of IgA and IgG antibodies in plasma and NPS appeared specific to each patient.ConclusionsAnti-N IgG and IgA antibodies are detected in NPS, and their levels are related to antibody levels in plasma. The two patients with severe disease exhibited different antibody profiles that may reflect different disease outcome. For the pauci-symptomatic patients, one showed a low anti-N IgG and IgA response in the plasma only, while the other one did not exhibit overt serological response.

Published
2021

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