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1. Trajectory of Serum Bilirubin Predicts Spontaneous Recovery in a Real-World Cohort of Patients With Alcoholic Hepatitis

Author: Francisco Bosques-Padilla, Ramon Bataller, Guadalupe Garcia-Tsao, Ashwin Dhanda, Michael R. Lucey, Juan Pablo Arab, Debbie L. Shawcross, Joaquín Cabezas, Robert S. Brown, Richard D. Parker, Bernd Schnabl, Ashish Sinha, P. Mathurin, Ian A. Rowe, Elizabeth C. Verna, José Altamirano, Meritxell Ventura-Cots, Andrew Holt, C Anne McCune, Marco Arrese, Victor Vargas, Alexandre Louvet, and Juan G. Abraldes
Subjects: medicine.medical_specialty, Bilirubin, medicine.drug_class, Spontaneous recovery, Alcoholic hepatitis, Severity of Illness Index, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Model for End-Stage Liver Disease, Liver Function Tests, Internal medicine, medicine, Humans, Hepatology, Hepatitis, Alcoholic, business.industry, Gastroenterology, Odds ratio, Prognosis, medicine.disease, Confidence interval, chemistry, 030220 oncology & carcinogenesis, Cohort, Corticosteroid, 030211 gastroenterology & hepatology, business
Abstract: Alcoholic hepatitis (AH) is a severe condition with poor short-term prognosis. Specific treatment with corticosteroids slightly improves short-term survival but is associated with infection and is not used in many centers. A reliable method to identify patients who will recover spontaneously will minimise the numbers of patients who experience side effects of available treatments.We analysed the trajectory of serum bilirubin concentration over the course of hospital admissions in patients with AH to predict spontaneous survival and the need for treatment.data from 426 patients were analysed. Based on bilirubin trajectory, patients were categorized into three groups: 'fast fallers' (bilirubin0.8 x admission value at day 7), 'static' (bilirubin of0.9 -1.2 x admission value) and 'rapid risers' (bilirubin of ≥1.2 x admission bilirubin). Fast fallers had significantly better 90-day survival compared to other groups (log rank p.001), and showed no benefit of corticosteroid therapy (OR for survival at 28 days of treatment, 0.94, 95% CI 0.06 - 8.41). These findings remained even amongst patients with severe disease based on initial DF, GAHS or MELD scores.We present an intuitive method of classifying patients with AH based on the trajectory of bilirubin over the first week of admission. It is complimentary to existing scores that identify candidates for corticosteroid treatment or assess response to treatment. This method identifies a group of patients with AH who recover spontaneously and can avoid corticosteroid therapy.
Published: 2022
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2. Téloméropathies de recrutement hématologique : étude de 15 cas

Author: A. Renaut-Marceau, F. Sicre de Fontbrune, M.-C. Willemin, Eric Hachulla, P. Antoine, Guillaume Lefèvre, A. Louvet, D. Launay, L. Terriou, S. Sanges, Elodie Lainey, V. Sobanski, C. Kannengiesser, and M.M. Farhat
Subjects: Gynecology, medicine.medical_specialty, business.industry, Gastroenterology, Internal Medicine, Medicine, business
Abstract: Resume Introduction Les telomeres sont composes d’une sequence repetee de nucleotides double brin TTAGGG et sont associes a de nombreuses proteines dont le complexe « Shelterin ». Leur role principal est de maintenir la stabilite du genome lors de la replication cellulaire grâce a un mecanisme de copie de la sequence repetee par le complexe telomerase. L’ensemble des pathologies impliquant une deregulation de la maintenance des telomeres sont maintenant reunies sous le terme de telomeropathies. L’objectif de notre etude etait de decrire les caracteristiques clinico-biologiques et therapeutiques dans une cohorte de patients atteints de telomeropathie de recrutement hematologique suivis en medecine interne au centre hospitalier universitaire de Lille. Methodes Il s’agit d’une etude retrospective, unicentrique realisee au sein du service de medecine interne-immunologie clinique, centre de reference des maladies auto-immunes et systemique rares au CHU de Lille entre 2005 et 2020 incluant l’ensemble des patients suivis pour telomeropathie. Resultats Des cas index et des apparentes ont ete inclus. Les 15 patients etudies etaient issus de 10 familles independantes. Soixante pour cent etaient porteurs d’une mutation du gene TERC a l’etat heterozygote. Soixante-sept pour cent avaient une atteinte hematologique comprenant notamment une macrocytose avec anemie et/ou thrombopenie, 20 % une atteinte hepatique et 27 % une atteinte pulmonaire de type fibrosante. L’immunophenotypage lymphocytaire montrait la presence d’une population lymphocytaire T double negative avec une expression de TCR γδ pour 5 (33 %) d’entre eux. Quarante-sept pour cent des patients n’avaient recu aucun traitement. Vingt-sept pour cent etaient sous androgene. Vingt pour cent avaient recu de la ciclosporine et 13 % du serum anti-lymphocytaire dans un contexte de diagnostic errone d’une aplasie acquise. Conclusion Il est important pour le medecin interniste d’etre sensibilise a la complexite des telomeropathies, diagnostic differentiel des aplasies medullaires acquises idiopathiques, pour pouvoir optimiser la prise en charge et eviter les therapeutiques inappropriees. L’allogreffe de cellules souches hematopoietiques est le seul traitement potentiellement curatif. Notre analyse a rapporte des particularites a l’immunophenotypage lymphocytaire non decrites a notre connaissance dont l’imputabilite physiopathologique reste a demontrer.
Published: 2022
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3. Research methodologies to address clinical unmet needs and challenges in alcohol‐associated liver disease

Author: Mark Thursz, Gyongyi Szabo, Allison J. Kwong, Suthat Liangpunsakul, Gerald Scott Winder, Vijay H. Shah, Craig J. McClain, Ashwani K. Singal, Alexandre Louvet, Pranoti Mandrekar, Norah A. Terrault, Paul Y. Kwo, W. Ray Kim, and Jessica L. Mellinger
Subjects: Hepatitis, medicine.medical_specialty, Alcohol Drinking, Hepatology, business.industry, medicine.medical_treatment, Alcohol use disorder, Liver transplantation, medicine.disease, Article, Liver Transplantation, Integrated care, Alcoholism, Liver disease, Clinical research, Internal medicine, Humans, Medicine, Prospective Studies, business, Intensive care medicine, Liver Diseases, Alcoholic, Disease burden
Abstract: Alcohol-associated liver disease (ALD) is emerging worldwide as the leading cause of liver-related morbidity, mortality, and indication for liver transplantation. The ALD Special Interest Group and the Clinical Research Committee at the digital American Association for the Study of Liver Diseases meeting in November 2020 held the scientific sessions to identify clinical unmet needs in ALD, and addressing these needs using clinical research methodologies. Of several research methodologies, the sessions were focused on (a) studying disease burden of ALD using large administrative databases, (b) developing biomarkers for noninvasive diagnosis of alcohol-associated hepatitis (AH) and estimation of disease prognosis, (c) identifying therapeutic targets for ALD and AH, (d) deriving accurate models to predict prognosis or posttransplant alcohol relapse as a basis for developing treatment algorithm and a uniform protocol on patient-selection criteria for liver transplantation, and (e) examining qualitative research methodologies in studying the barriers to implementation of multidisciplinary integrated care model by hepatology and addiction teams for the management of dual pathology of liver disease and of alcohol use disorder. Prospective multicenter studies are required to address many of these clinical unmet needs. Further, multidisciplinary care models are needed to improve long-term outcomes in patients with ALD.
Published: 2021
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4. Sarcopenia should be evaluated in patients with acute-on-chronic liver failure and candidates for liver transplantation

Author: Florent Artru, Alexandre Louvet, Faouzi Saliba, Georges-Philippe Pageaux, and Charles le Goffic
Subjects: medicine.medical_specialty, Cirrhosis, Hepatology, business.industry, medicine.medical_treatment, Liver transplantation, medicine.disease, Gastroenterology, Sarcopenia, Internal medicine, Medicine, Acute on chronic liver failure, In patient, business
Published: 2022
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5. Severe acute respiratory syndrome coronavirus 2 vaccination for patients with solid cancer: Review and point of view of a French oncology intergroup (GCO, TNCD, UNICANCER)

Author: Jean-Yves Blay, Virgine Westeel, Khê Hoang-Xuan, Philippe Gorphe, Thomas Aparicio, Thierry Lecomte, David Tougeron, Astrid Lièvre, Pierre Michel, Sébastien Gaujoux, Amélie Servettaz, Pascale Mariani, Maxime Hentzien, Michel Ducreux, Léon Maggiori, Firouzé Bani-Sadr, Laura Mansi, Jean Bourhis, Olivier Bouché, Boris Guiu, Christophe Louvet, Florence Huguet, Barbara Seitz-Polski, Juliette Thariat, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de cancérologie cervico-faciale [Gustave Roussy] (CCF), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Universitaire de Cancérologie [Sorbonne Université] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Département d'hépato-gastro-entérologie [Hôpital Trousseau : CHRU Tours], Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cooperator Multidisciplinary Oncology Group (GERCOR), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut Curie [Paris], Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Léon Bérard [Lyon], None, University Hospital of Montpellier, Institut Universitaire de Cancérologie [Paris] (IUC), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Jonchère, Laurent, CHU Trousseau [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-CHU Trousseau [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: 0301 basic medicine, Cancer Research, Pediatrics, medicine.medical_specialty, COVID-19 Vaccines, medicine.medical_treatment, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Neutropenia, medicine.disease_cause, Current Perspective, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Neoplasms, Pandemic, medicine, Humans, Chemotherapy, education, Coronavirus, education.field_of_study, Radiotherapy, SARS-CoV-2, business.industry, Vaccination, COVID-19, Cancer, medicine.disease, 3. Good health, Radiation therapy, Solid cancers, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, business
Abstract: International audience; The impacts of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on cancer care are multiple, entailing a high risk of death from coronavirus disease 2019 (COVID-19) in patients with cancer treated by chemotherapy. SARS-CoV-2 vaccines represent an opportunity to decrease the rate of severe COVID-19 cases in patients with cancer and also to restore normal cancer care. Patients with cancer to be targeted for vaccination are difficult to define owing to the limited contribution of these patients in the phase III trials testing the different vaccines. It seems appropriate to vaccinate not only patients with cancer with ongoing treatment or with a treatment having been completed less than 3 years ago but also household and close contacts. High-risk patients with cancer who are candidates for priority access to vaccination are those treated by chemotherapy. The very high-priority population includes patients with curative treatment and palliative first- or second-line chemotherapy, as well as patients requiring surgery or radiotherapy involving a large volume of lung, lymph node and/or haematopoietic tissue. When possible, vaccination should be carried out before cancer treatment begins. SARS-CoV-2 vaccination can be performed during chemotherapy while avoiding periods of neutropenia and lymphopenia. For organisational reasons, vaccination should be performed in cancer care centres with messenger RNA vaccines (or non-replicating adenoviral vaccines in non-immunocompromised patients). Considering the current state of knowledge, the benefit-risk ratio strongly favours SARS-CoV-2 vaccination of all patients with cancer. To obtain more data concerning the safety and effectiveness of vaccines, it is necessary to implement cohorts of vaccinated patients with cancer.
Published: 2021
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6. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial

Author: Thierry Conroy, Jean-François Bosset, Pierre-Luc Etienne, Emmanuel Rio, Éric François, Nathalie Mesgouez-Nebout, Véronique Vendrely, Xavier Artignan, Olivier Bouché, Dany Gargot, Valérie Boige, Nathalie Bonichon-Lamichhane, Christophe Louvet, Clotilde Morand, Christelle de la Fouchardière, Najib Lamfichekh, Béata Juzyna, Claire Jouffroy-Zeller, Eric Rullier, Frédéric Marchal, Sophie Gourgou, Florence Castan, Christophe Borg, Philippe Ronchin, Jean-François Seitz, Stéphane Corbinais, Emmanuel Maillard, Monique Noirclerc, Farid El Hajbi, Anne-Laure Villing, Yves Bécouarn, Lam Foong Fat Lam Kam Sang, Pascal Artru, Jean-Baptiste Bachet, Fayçal Hocine, Catherine Ligeza-Poisson, Claire Vautravers, Meher Ben Abdelghani, Thomas Aparicio, Elise Desot, and Isabelle Marquis
Subjects: Adult, Male, medicine.medical_specialty, FOLFIRINOX, medicine.medical_treatment, Population, Leucovorin, Irinotecan, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Adjuvant therapy, Humans, 030212 general & internal medicine, education, Neoadjuvant therapy, Aged, education.field_of_study, Performance status, Rectal Neoplasms, business.industry, Chemoradiotherapy, Middle Aged, Total mesorectal excision, Neoadjuvant Therapy, Oxaliplatin, Oncology, 030220 oncology & carcinogenesis, Quality of Life, Female, Fluorouracil, business, medicine.drug
Abstract: Summary Background Treatment of locally advanced rectal cancer with chemoradiotherapy, surgery, and adjuvant chemotherapy controls local disease, but distant metastases remain common. We aimed to assess whether administering neoadjuvant chemotherapy before preoperative chemoradiotherapy could reduce the risk of distant recurrences. Methods We did a phase 3, open-label, multicentre, randomised trial at 35 hospitals in France. Eligible patients were adults aged 18–75 years and had newly diagnosed, biopsy-proven, rectal adenocarcinoma staged cT3 or cT4 M0, with a WHO performance status of 0–1. Patients were randomly assigned (1:1) to either the neoadjuvant chemotherapy group or standard-of-care group, using an independent web-based system by minimisation method stratified by centre, extramural extension of the tumour into perirectal fat according to MRI, tumour location, and stage. Investigators and participants were not masked to treatment allocation. The neoadjuvant chemotherapy group received neoadjuvant chemotherapy with FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and fluorouracil 2400 mg/m2 intravenously every 14 days for 6 cycles), chemoradiotherapy (50 Gy during 5 weeks and 800 mg/m2 concurrent oral capecitabine twice daily for 5 days per week), total mesorectal excision, and adjuvant chemotherapy (3 months of modified FOLFOX6 [intravenous oxaliplatin 85 mg/m2 and leucovorin 400 mg/m2, followed by intravenous 400 mg/m2 fluorouracil bolus and then continuous infusion at a dose of 2400 mg/m2 over 46 h every 14 days for six cycles] or capecitabine [1250 mg/m2 orally twice daily on days 1–14 every 21 days]). The standard-of-care group received chemoradiotherapy, total mesorectal excision, and adjuvant chemotherapy (for 6 months). The primary endpoint was disease-free survival assessed in the intention-to-treat population at 3 years. Safety analyses were done on treated patients. This trial was registered with EudraCT (2011-004406-25) and ClinicalTrials.gov ( NCT01804790 ) and is now complete. Findings Between June 5, 2012, and June 26, 2017, 461 patients were randomly assigned to either the neoadjuvant chemotherapy group (n=231) or the standard-of-care group (n=230). At a median follow-up of 46·5 months (IQR 35·4–61·6), 3-year disease-free survival rates were 76% (95% CI 69–81) in the neoadjuvant chemotherapy group and 69% (62–74) in the standard-of-care group (stratified hazard ratio 0·69, 95% CI 0·49–0·97; p=0·034). During neoadjuvant chemotherapy, the most common grade 3–4 adverse events were neutropenia (38 [17%] of 225 patients) and diarrhoea (25 [11%] of 226). During chemoradiotherapy, the most common grade 3–4 adverse event was lymphopenia (59 [28%] of 212 in the neoadjuvant chemotherapy group vs 67 [30%] of 226 patients in the standard-of-care group). During adjuvant chemotherapy, the most common grade 3–4 adverse events were lymphopenia (18 [11%] of 161 in the neoadjuvant chemotherapy group vs 42 [27%] of 155 in the standard-of-care group), neutropenia (nine [6%] of 161 vs 28 [18%] of 155), and peripheral sensory neuropathy (19 [12%] of 162 vs 32 [21%] of 155). Serious adverse events occurred in 63 (27%) of 231 participants in the neoadjuvant chemotherapy group and 50 (22%) of 230 patients in the standard-of-care group (p=0·167), during the whole treatment period. During adjuvant therapy, serious adverse events occurred in 18 (11%) of 163 participants in the neoadjuvant chemotherapy group and 36 (23%) of 158 patients in the standard-of-care group (p=0·0049). Treatment-related deaths occurred in one ( Interpretation Intensification of chemotherapy using FOLFIRINOX before preoperative chemoradiotherapy significantly improved outcomes compared with preoperative chemoradiotherapy in patients with cT3 or cT4 M0 rectal cancer. The significantly improved disease-free survival in the neoadjuvant chemotherapy group and the decreased neurotoxicity indicates that the perioperative approach is more efficient and better tolerated than adjuvant chemotherapy. Therefore, the PRODIGE 23 results might change clinical practice. Funding Institut National du Cancer, Ligue Nationale Contre le Cancer, and R&D Unicancer.
Published: 2021
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7. Acute Liver Injury With Therapeutic Doses of Acetaminophen: A Prospective Study

Author: Marion Khaldi, Sébastien Dharancy, Line Carolle Ntandja Wandji, Alexandre Louvet, Guillaume Lassailly, Benoît Quesnel, Elise Lemaître, Philippe Mathurin, Florent Artru, and Claire Lafforgue
Subjects: Adult, Male, 0301 basic medicine, Drug, medicine.medical_specialty, Alcohol Drinking, Bilirubin, media_common.quotation_subject, Population, Gastroenterology, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Disease severity, Risk Factors, Internal medicine, medicine, Humans, Prospective Studies, education, Prospective cohort study, Acetaminophen, media_common, Liver injury, Acute liver injury, education.field_of_study, Hepatology, business.industry, digestive, oral, and skin physiology, Age Factors, Patient Acuity, Analgesics, Non-Narcotic, Middle Aged, medicine.disease, 030104 developmental biology, chemistry, Female, 030211 gastroenterology & hepatology, Chemical and Drug Induced Liver Injury, business, medicine.drug
Abstract: BACKGROUND AND AIMS Because of the extensive use of this drug, further evaluation of acute liver injury (ALI) with therapeutic doses of acetaminophen (APAP; ≤6 g/d) is required. We characterize ALI with therapeutic doses of APAP and determine the host factors associated with disease severity and the predictors of outcome. APPROACH AND RESULTS All patients admitted with severe APAP-related ALI in our center were included from 2002 to 2019, either attributable to therapeutic doses or overdose. ALI with therapeutic doses (ALITD) was defined as APAP intake
Published: 2021
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8. Alcoholic hepatitis: Towards an era of personalised management

Author: Delphine Degré, Christophe Moreno, Line C Ntandja Wandji, and Alexandre Louvet
Subjects: medicine.medical_specialty, medicine.diagnostic_test, business.industry, medicine.medical_treatment, Gastroenterology, Alcoholic hepatitis, macromolecular substances, Disease, Liver transplantation, Jaundice, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Liver biopsy, Internal medicine, medicine, Prednisolone, 030211 gastroenterology & hepatology, medicine.symptom, Recent onset, business, Medical therapy, medicine.drug
Abstract: Alcoholic hepatitis should be suspected in every patient with excessive chronic alcohol consumption and recent onset of jaundice. Diagnosis of alcoholic hepatitis is based on clinical and laboratory findings, and confirmed by a liver biopsy when available. Several scores are available to assess severity and prognosis of alcoholic hepatitis. The 1-month mortality of patients with severe alcoholic hepatitis, as defined by Maddrey's discriminant function, is 20-30%. Therefore, severe alcoholic hepatitis should be treated with a 28-day course of oral prednisolone after systematic screening for infection. In this review, we discuss diagnosis of alcoholic hepatitis, the different scores to assess severity of the disease, indications for corticosteroid therapy and alternative therapeutic options for non-responders to medical therapy.
Published: 2020
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9. CA-125 ELIMination Rate Constant K (KELIM) Is a Marker of Chemosensitivity in Patients with Ovarian Cancer: Results from the Phase II CHIVA Trial

Author: Philippe Follana, Pierre Combe, Eric Pujade-Lauraine, Alexandra Leary, Patrick Robelin, Gilles Freyer, Michel Fabbro, Nathalie Bonichon-Lamichhane, Christophe Desauw, Olivier Colomban, Christophe Louvet, Jean-Emmanuel Kurtz, Gwenael Ferron, M. Leheurteur, Annick Chevalier-Place, Benoit You, Gaëtan de Rauglaudre, Isabelle Ray-Coquard, Jean-Pierre Lotz, Sophie Abadie-Lacourtoisie, Florence Joly, Francesco Del Piano, and Michel Tod
Subjects: Adult, Oncology, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Logistic regression, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Elimination rate constant, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, In patient, 030212 general & internal medicine, Aged, Neoplasm Staging, Ovarian Neoplasms, Chemotherapy, business.industry, Cytoreduction Surgical Procedures, Middle Aged, medicine.disease, Debulking, Neoadjuvant Therapy, Progression-Free Survival, Regimen, chemistry, Drug Resistance, Neoplasm, CA-125 Antigen, 030220 oncology & carcinogenesis, Female, Nintedanib, Ovarian cancer, business
Abstract: Purpose: In patients with ovarian cancer receiving neoadjuvant chemotherapy, the first-line treatment success will depend on both the tumor-primary chemosensitivity and the completeness of interval debulking surgery (IDS). The modeled CA-125 ELIMination rate constant K (KELIM), calculated with the CA-125 longitudinal kinetics during the first 100 chemotherapy days, is a validated early marker of tumor chemosensitivity. The objective was to investigate the role of the chemosensitivity relative to the success of first-line medical–surgical treatment. Experimental Design: The CA-125 concentrations were prospectively measured in the randomized phase II trial CHIVA (NCT01583322, carboplatin–paclitaxel regimen ± nintedanib, and IDS, n = 188 patients). The KELIM predictive value regarding the tumor response rate, likelihood of complete IDS, risk of subsequent platinum-resistant relapse (PtRR), progression-free survival (PFS), and overall survival (OS) was assessed using univariate and multivariate tests. Results: The data from 134 patients were analyzed. KELIM was an independent and major predictor of subsequent PtRR risk, and of survivals. The final logistic regression model, including KELIM [OR = 0.13; 95% confidence interval (CI), 0.03–0.49] and complete IDS (no vs. yes, OR = 0.30; 95% CI, 0.11–0.76) highlights the preponderant role of chemosensitivity on the success of the first-line treatment. In patients with highly chemosensitive diseases, the patient prognosis was driven more by the chemotherapy-induced antitumor effects than by the surgery. Conclusions: The tumor-primary chemosensitivity, assessed by the modeled CA-125 KELIM calculated during neoadjuvant chemotherapy (http://www.biomarker-kinetics.org/CA-125-neo), may be a major parameter to consider for decision-making regarding IDS attempt, and selecting patients for treatments meant to reverse the primary chemoresistance. See related commentary by May and Oza, p. 4432
Published: 2020
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10. Does Chemotherapy-Induced Liver Injury Impair Postoperative Outcomes After Laparoscopic Liver Resection for Colorectal Metastases?

Author: Maud Neuberg, David Fuks, Marine Lefevre, Brice Gayet, Anthony Sarran, Christophe Louvet, Ioannis Triantafyllidis, Marc Beaussier, and Mostefa Bennamoun
Subjects: medicine.medical_specialty, Cirrhosis, medicine.medical_treatment, Antineoplastic Agents, Subgroup analysis, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Hepatectomy, Humans, Pathological, Retrospective Studies, Liver injury, Chemotherapy, business.industry, Liver Neoplasms, Perioperative, medicine.disease, Liver, 030220 oncology & carcinogenesis, Laparoscopy, 030211 gastroenterology & hepatology, Surgery, Steatohepatitis, Colorectal Neoplasms, business, Nodular regenerative hyperplasia
Abstract: Chemotherapy-associated liver injuries (CALI) have been associated with poor postoperative outcome after open liver resection. To date, no data concerning any correlation of CALI and laparoscopic liver resection (LLR) are available. In the present study, we evaluated the impact of CALI on short-term outcomes in patients undergoing LLR. All patients who underwent in our department LLR for colorectal liver metastases (CRLM) from 2000 to 2016 were retrospectively reviewed. Patients were divided in 4 groups according to their pathological histology. In group 1 patients had normal liver parenchyma. Group 2 included patients with steatosis and steatohepatitis. Patients with sinusoidal obstruction syndrome (SOS) and nodular regenerative hyperplasia (NRH) were allocated to group 3, whereas the remaining with fibrosis and cirrhosis, were assigned to group 4. A total of 490 LLR for CRLM were included in the study. Perioperative details and morbidity did not differ significantly between the four groups. Subgroup analysis showed that NRH was associated with higher amount of blood loss (p = 0.043), overall (p = 0.021) and liver-specific morbidity (p = 0.039). NRH is a severe form of CALI that may worsen the short-term outcomes of patients undergoing LLR for CRLM. However, the remaining forms of CALI do not have a significant impact on perioperative outcomes after LLR.
Published: 2020
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11. Patients atteints d’un cancer gastrique localisé MSI/dMMR, pas de chimiothérapie mais une immunothérapie périopératoire : l’essai de phase II GERCOR NEONIPIGA vient d’être ouvert au recrutement

Author: Thierry André, Aziz Zaanan, Christophe Borg, Alex Duval, David Tougeron, Marine Jary, Rosine Guimbaud, Lea Clavel, Romain Cohen, Thomas Aparicio, Antoine Adenis, Christophe Louvet, Christophe Tournigand, Benoist Chibaudel, Jaafar Benouna, Marie-Line Garcia-Larnicol, Xavier Dray, Harry Sokol, Magali Svrcek, Thomas Pudlarz, Dewi Vernerey, Guillaume Piessen, Service d'Oncologie Médicale [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), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Cooperator Multidisciplinary Oncology Group (GERCOR), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Claude Huriez [Lille], CHU Lille, 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), Université Sorbonne Paris Cité (USPC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Mutualiste de Montsouris (IMM), Service d'Oncologie médicale [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Toulouse [Toulouse], Centre hospitalier universitaire de Nantes (CHU Nantes), Institut du Cancer de Montpellier (ICM), 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), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Instabilité des microsatellites et cancers [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], and Service de Pathologie [CHU Saint-Antoine]
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Ipilimumab, 03 medical and health sciences, 0302 clinical medicine, medicine, Radiology, Nuclear Medicine and imaging, 10. No inequality, Syndrome de Lynch, Gynecology, business.industry, Hematology, General Medicine, Instabilité des microsatellites, 3. Good health, Lynch syndrome, Nivolumab, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Microsatellite instability, Cancer de l’estomac, Gastric cancer, business, medicine.drug
Abstract: International audience; IntroductionPerioperative chemotherapy is the standard strategy for localized gastric cancers. Nevertheless, this strategy seems to be inefficient, if not deleterious, for patients with tumors harboring microsatellite instability (MSI) and/or mismatch repair deficiency (dMMR), a tumor phenotype predictive for the efficacy of immune checkpoint inhibitors (ICKi).AimThe GERCOR NEONIPIGA single-arm phase II study (NCT04006262; EUDRACT 2018-004712-22) aims at evaluating the efficacy of a peri-operative strategy with nivolumab and ipilimumab in neoadjuvant setting, then nivolumab alone after surgery for patients with resectable MSI/dMMR gastric cancer.Material and methodsMain inclusion criteria are: gastric and oesogastric junction adenocarcinoma (GOA), T2-T4, all N stage and M0, MSI/dMMR. Patients will be treated with nivolumab 240 mg Q2 W, 6 infusions, and ipilimumab 1 mg/kg Q6 W, 2 infusions in neoadjuvant setting. Following surgery, patients with TRG 1-2-3 (Mandard tumor regression grade), acceptable tolerance of neoadjuvant treatment and postoperative ECOG performance status 0–1, will be treated with adjuvant nivolumab 480 mg Q4 W, 9 infusions.ResultsThe primary endpoint is pathological complete response rate (pCR-R). Based on a Fleming design, with α = 5% and β = 20%, 27 patients have to be evaluated (H0 = 5%; H1 = 20%). Secondary endpoints include disease-free survival, overall survival and safety.ConclusionThis study is planned to include 32 patients to evaluate the pCR-R with the combination of nivolumab and ipilimumab in neoadjuvant setting for MSI/dMMR localized GOA. The MSI/MMR status should be systematically assessed on diagnostic biopsies of all GOA. If it meets its primary endpoint, the GERCOR NEONIPIGA study might mark a turning point in the management of localized MSI/dMMR GOA patients.; IntroductionLa chimiothérapie périopératoire est la stratégie de référence pour les cancers gastriques (CG) localisés, mais semble inefficace voire délétère pour les patients avec un cancer MSI/dMMR (microsatellites instables/MMR-déficient), biomarqueur prédictif de l’efficacité de l’immunothérapie.ObjectifL’essai de phase 2 mono-bras GERCOR NEONIPIGA (NCT04006262; EUDRACT 2018-004712-22) évalue l’efficacité du nivolumab plus ipilimumab en néo-adjuvant puis nivolumab seul en adjuvant pour les CG ou de la jonction œsogastrique (JOG) MSI/dMMR résécables.Matériel et méthodesLes principaux critères d’inclusion sont : CG/JOG, T2-4 tout N M0, MSI/dMMR. Les patients sont traités en néo-adjuvant par nivolumab 240 mg Q2 W, 6 perfusions, et ipilimumab 1 mg/kg Q6 W, deux injections. Les patients avec un degré de régression tumorale 1-3 selon Mandard, une tolérance acceptable du traitement néo-adjuvant et un indice de performance postopératoire ECOG 0-1 recevront neuf perfusions mensuelles de nivolumab 480 mg en adjuvant.RésultatsL’objectif principal est le taux de réponse complète pathologique (pCR). Selon un design de Fleming avec α = 5 % et β = 20 %, 27 patients évaluables sont à analyser (H0 = 5 % ; H1 = 20 %). Les critères secondaires de jugement sont la survie sans maladie, la survie globale et le profil de tolérance.ConclusionIl est prévu d’inclure 32 patients pour évaluer le taux de pCR pour les CG/JOG MSI/dMMR traités par nivolumab et ipilimumab néo-adjuvant. Le statut MSI/MMR doit être systématiquement analysé sur les biopsies diagnostiques de tout CG/JOG. L’étude NEONIPIGA pourrait marquer un tournant dans la prise en charge des CG/JOG MSI/dMMR si elle atteint son objectif principal.
Published: 2020
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12. Nal-IRI/LV5-FU versus paclitaxel as second-line therapy in patients with metastatic esophageal squamous cell carcinoma (OESIRI)-PRODIGE 62: A multicentre, randomised, non-comparative phase II study

Author: Laetitia Dahan, Emilie Barbier, David Tougeron, Jean Philippe Metges, Samy Louafi, Christophe Borg, Roger Faroux, Lila Gaba, Christophe Louvet, Jérôme Desramé, Astrid Lièvre, Violaine Randrian, Frédéric Di Fiore, Sylvain Manfredi, Antoine Adenis, Gilles Breysacher, Pierre Laurent-Puig, Laurent Mineur, Guillaume Roquin, Anthony Lopez, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Hôpital privé Jean Mermoz, Fédération Francophone de la Cancérologie Digestive, FFCD, Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut Sainte Catherine [Avignon], Hôpital Louis Pasteur [Colmar] (CH Colmar), Servier, Faculté de Médecine - Clermont-Auvergne (FM - UCA), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Oncology, medicine.medical_specialty, Esophageal Neoplasms, Paclitaxel, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Esophageal cancer, Phases of clinical research, Irinotecan, 03 medical and health sciences, chemistry.chemical_compound, Clinical Trials, Phase II as Topic, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Multicenter Studies as Topic, ComputingMilieux_MISCELLANEOUS, Randomized Controlled Trials as Topic, 030304 developmental biology, Cisplatin, 0303 health sciences, Chemotherapy, Hepatology, Performance status, business.industry, Gastroenterology, medicine.disease, 3. Good health, Survival Rate, chemistry, Docetaxel, 030220 oncology & carcinogenesis, Disease Progression, Quality of Life, Squamous cell cancer, Esophageal Squamous Cell Carcinoma, Fluorouracil, France, Neoplasm Recurrence, Local, business, medicine.drug
Abstract: Half of patients newly diagnosed with esophageal squamous cell cancer (ESCC) have metastatic disease (mESCC) and therefore a poor prognosis. Furthermore, half of patients with initial loco-regional disease present disease recurrence after surgery and/or chemoradiation. In mESCC, the recommended first-line treatment combines 5-fluorouracil and cisplatin, although this has not been validated by a phase III trial. Patients with disease progression or recurrence after platinum-based chemotherapy and good performance status probably benefit from second-line chemotherapy. Several molecules have been evaluated in phase I/II trials or retrospective studies (docetaxel, paclitaxel and irinotecan) but no randomised studies are available. OESIRI is a multicentre, randomised, open-label phase II trial designed to evaluate efficacy and safety of liposomal irinotecan (nal-IRI) plus 5-FU versus paclitaxel as second-line therapy in patients with mESCC. The main inclusion criteria are histologically proven mESCC in progression after first-line platinum-based chemotherapy. Patients with initial resectable disease can be included if recurrence occurred within 6 months. The primary objective is to evaluate the percentage of patients alive 9 months after randomisation. Secondary endpoints are progression-free survival, overall survival, response rate, safety and quality of life. In addition, circulating tumour DNA will be monitored to assess its prognostic value.
Published: 2020
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13. Regorafenib or Tamoxifen for platinum-sensitive recurrent ovarian cancer with rising CA125 and no evidence of clinical or RECIST progression: A GINECO randomized phase II trial (REGOVAR)

Author: Mathilde Cancel, Oana Pop, Alain Lortholary, C.B. Levaché, Daniel Pissaloux, Magali Provansal, Elsa Kalbacher, Rémy Largillier, Amélie Anota, Audrey Lardy-Cleaud, Jérôme Meunier, Christophe Louvet, Anne-Claire Hardy-Bessard, Aurélie Houlier, Marie-Ange Mouret-Reynier, Fabien Brocard, Benoit You, Anne Floquet, Cyril Abdeddaim, Aude-Marie Savoye, Isabelle Ray-Coquard, Alain Zannetti, Laurence Venat-Bouvet, Isabelle Treilleux, Olivier Tredan, Jean-Sebastien Frenel, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)
Subjects: Oncology, Adult, medicine.medical_specialty, Pyridines, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, Disease-Free Survival, Targeted therapy, chemistry.chemical_compound, Regorafenib, Internal medicine, Clinical endpoint, Biomarkers, Tumor, Medicine, Humans, education, Response Evaluation Criteria in Solid Tumors, Aged, Platinum, Aged, 80 and over, Ovarian Neoplasms, education.field_of_study, business.industry, Phenylurea Compounds, Obstetrics and Gynecology, Cancer, Middle Aged, medicine.disease, Tamoxifen, Treatment Outcome, chemistry, CA-125 Antigen, Toxicity, Female, Neoplasm Recurrence, Local, business, Ovarian cancer, medicine.drug
Abstract: Objective To evaluate the efficacy and safety of regorafenib versus tamoxifen in platinum-sensitive ovarian cancer biological recurrence, defined by CA-125 increase without radiological (RECIST criteria) or symptomatic evidence of progression. Patients and methods 116 patients with platinum-sensitive ovarian cancer presenting an isolated increase of CA-125 were planned to be randomized. Regorafenib was administered orally at 160 or 120 mg daily, 3 weeks on/1 week off or tamoxifen at 40 mg daily, until disease progression or development of unacceptable toxicity. The primary endpoint was Progression-Free Survival, assessed by progression according to RECIST 1.1 or death (by any cause). Secondary endpoints included Overall Survival, Best Response and CA-125 response rate. Results 68 patients were randomized. Median age was 67 years (range: 30-87). Primary site of cancer was ovarian for most patients (92.6%). Tumors were predominantly serous / (89.7%), high grade (83.6%) and initial FIGO staging was III for 69.6% of the patients. Most (79.4%) patients were included after the first line of platinum-based treatment. After a median follow-up of 32 months, there was no difference of progression-free survival (PFS) between regorafenib and tamoxifen groups (p = 0.72), with median PFS of 5.6 months (CI 90%: 3.84-7.52) for the tamoxifen arm and 4.6 months (CI 90%: 3.65-7.33) for the regorafenib arm. There was also no difference in term of overall survival, best response or CA-125 response, delay to next therapy. Regorafenib presented a less favorable safety profile than tamoxifen, with grade 3/4 events occurring for 90.9% of the patients compared to 54.3% for tamoxifen. The most frequent were cutaneous, digestive, and biological events. Notably, hand-foot syndrome occurred in 36.4% of these patients. Conclusion Regorafenib presented an unfavorable toxicity profile compared to tamoxifen, with no superior efficacy in this population of patients.
Published: 2022
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14. Risk factors for Coronavirus Disease 2019 (COVID-19) severity and mortality among solid cancer patients and impact of the disease on anticancer treatment: A French nationwide cohort study (GCO-002 CACOVID-19)

Author: Astrid Lièvre, Anthony Turpin, Isabelle Ray-Coquard, Karine Le Malicot, Juliette Thariat, Guido Ahle, Cindy Neuzillet, Xavier Paoletti, Olivier Bouché, Kais Aldabbagh, Pierre Michel, Didier Debieuvre, Anthony Canellas, Marie Wislez, Lucie Laurent, May Mabro, Raphael Colle, Anne-Claire Hardy-Bessard, Laura Mansi, Emeline Colomba, Jean Bourhis, Philippe Gorphe, Yoann Pointreau, Ahmed Idbaih, Renata Ursu, Anna Luisa Di Stefano, Gérard Zalcman, Thomas Aparicio, Solenne Moulin, Olivier Leleu, Sylvie Leparree, Henri Goasdoue, Christine Piprot, Gerald Tourneur, Vincent Bayart, Delphine Lignier, Emma Lachaier, Marwa Khamari, Alexandre Coutte, Nicolas Siembida, Aline Houessinon, Jean Marc Regimbeau, Bruno Chauffert, Aurélie Moreira, Vincent Hautefeuille, Christine Hee, Mathieu Boone, Céline Bihan, Emilie Chive, Stéphane Poulet-Potriquier, Rachida Fahem, Dominique Luet, Guillaume Roquin, Carole Vitellius, Nathanaëlle Cornet-Trichereau, François-Xavier Caroli-Bosc, Anne Thirot-Bidault, Stanislas Ropert, Julie Gachet - Masson, Mélanie Dehais, Gwen-Ael L'helgoualc'h, Ibrahim Ali-Mahamadou, Safia Talfi, Laure Belmont, Dieudonné Kilendo, Nasro Benrezzak, Emeline Dubief, Guillaume Conroy, Laurence Delique, Maud Basso, Isabelle Pons, Karine Salignon, Anne-Laure Villing, Emmanuelle Mougenot, Cassandra Porebski, Asma Guiatni, Nicolas Cloarec, Laurent Mineur, Marie Bouchaud, Céleste David, Annie Peytier, Thomas Greletty, Franck Audemar, Emanuelle Vignes, Floriane Minne, Guillaume Goldzak, Fabienne Huysman, Fayçal Hocine, Zaher Lakkis, Guillaume Meynard, Hamadi Almotlak, Elodie Klajer, Xu-Shan Sun, Julie Wasselin, Pascale Catala, Claire Mazuy, Hélène Vandamme, Jean-Briac Prevost, Aurélie Fadin, Laurent Basson, Jean-Baptiste Huguet, Emmanuelle Dos Santos, Bérangère Jany, Alain Saad, Frédéric Goutorbe, Eric Oziol, Mohamed Ramdani, Ouafae Kadiri, Delphine Garbay, Clotilde Huet, Etienne Giroux Leprieur, Wen Teng, Justine Monvoisin, Patrick Arnaud Coffin, Sylvie Roux, Hubert Orfeuvre, Mélanie Chagros, Didier Pillon, Agathe Rassoul, Pierre Guillaume Poureau, Cécile Novello, François Ducray, Cécile Trouba, Vianney Bastit, Emmanuel Babin, Vincent Leon, Anne-Catherine Courtecuisse, Julie Vambre, Vincent Tack, Christophe Desauw, Fatima Meniai, Christina Peres, Aurélie Esparcieux, Hervé Perrier, Nathalie Doux, Régis Kaphan, Bertrand Roques, Christine Rebischung, Dominique Mille, Gaëlle Fernandes, Naceur Abdelli, Natacha Jousset, Pierre Combe, Eric Jonveaux, Patrick Dumont, Marc Kanaan, Corinne Berthelot Gras, Valérie Panis, Laure Kaluzinski, Marjolène Venant-Valery, You-Heng Lam, Laura Vallee, Frédéric Riviere, Muriel Durand, Dihya Benghadid, Emilie Villeneuve, Olivia Hentic Dhome, Zedjiga Bounouar, Louis De Mestier, Jacqueline Dubois, Magali Eyriey, Lionel Moreau, Dib Baihas, Kaïs Aldabbagh, Dominique Degriffolet, Virginie Sebbagh, Jean-Christophe Seghezzi, Marion Lozach-Brugirard, Julie Mandrou, Loubna Mavier, Florence Hennetier, Jean-Philippe Wagner, Elisabeth Carola, Karthiga Chandirakumaran, Sandrine Loutski, Isabelle Cojean-Zelek, Amina Bouras, Sandrine Lacour, Fahem Froura, Hadjer Ben Nadji, Sophie Cattelain, Franck Darloy, Geneviève Jolimoy Boilleau, Cyrielle Maissiat, Ariane Darut-Jouve, Véronique Lorgis, Ikram Charifi-Alaoui, François Ghiringhelli, Antoine Drouillard, Marie Chaix, Sylvain Manfredi, Côme Lepage, Alice Gagnaire, Marianne Latournerie, Sofia jourdan, Nora Perrot, Mireille folia, Anne Minello, Jean-Louis Jouve, Marielle Fery, Alain Landau, Diane Evrard, Bruno Valenza, Jean-François Paitel, Laetitia Chablais, Thomas Kreitmann, Laurence Lancry-Lecomte, Adrien Monard, Eve Faugeras, Paul Boucheret, Cécile Glommeau, Christine Tchikladze, Claire Garnier Tixidre, Jérôme Long, Manel Zaidi, Véronique Delabarre, Juliette Meyzenc, Loïc Ferrand, Denis Moro-Sibilot, Paul Bouheret, Cécile Leyronnas, Camille Herve, Audrey Thoor, Emanuelle Jacquet, Gaël Roth, Videsheka Madapathage-Senanyake, Peggy Chupeau, Elsa Bieber, Maud Rosso, Isabelle Lepage, Frank Priou, Margot Laly, Sylvie Aprelon, Natacha Sobolak, Helen Homokos, Fabienne Watelle, Alice Pham-Becker, Géraldine Lauridant, Charlotte Dujardin, Etienne Lenglin, Aimée Nienguet Tsota, Sophie Dominguez, Alexandra Forestier, Franck Nouvel, Justine Lerooy, Céline Ratajczak, Olivier Romano, Dorothéee Brzyski, Aurélien Barriere, Dominique Genet, Julien Tisse, Xavier Zasadny, Adeline Grelet, Amélie Hennion-Imbault, Eglantine Haustraete, Samy Louafi, Manal Awad, Younes Zekri, Caroline Cheneau, Nolwen Leissen, Joëlle Egreteau, Alexandra Breant, Matthieu Sarabi, Stéphanie Labonne, Julien Forestier, Céline Leclercq, Florence Prunier-Bossion, Isabelle Ray Coquard, Marielle Guillet, Aurélie Theillaumas, Emilie Prome, Thomas Walter, Pierre Philouze, Melody Lawo, Solène De Talhouet, Johanne Beuvelot, Yann Molin, Marie Bellecoste Martin, Maud Saussereau, Lauren Agnelli, Nicolas Fakhry, Christophe Laplace, Emmanuelle Norguet Monnereau, Céline Boucard, Kahina Djenad, Catherine Fontaine, Jean-François Seitz, Laétitia Dahan, Julie Sigrand, Muriel Duluc, Christophe Locher, Marjory Fleury, Ange Brou Marie, Ramdane Berkane, Séverine Poupblanc, Dominique Auby, Daniela Petran, Patrick Texereau, Elodie Guerineau, Morgan Andre, Linda Mahjoubi, Fanny Sarrazin, Sonia Jeanson, Anthony Gschwend, Virginie Birr, Mathieu Fore, Monique Noirclerc, Sihem Dahou, Dominique Spaeth, Mélanie Lambotin, Thomas Lelu, Benjamin Linot, Nathalie Hugon, Dominique Rousseau, Hélène Castanie, Carole Lenne, Alain Lortholary, Anatole Cessot, Messaouda Merzoug, Cécile Naudin, Jean-Michel Vannetzel, Ghina Aziz, Yacine Hadj Arab, Stéphanie Pernes, Isabelle Roche-Lachaise, Frédéric Fiteni, Hadjer Yahiaoui, Gwendoline Marel Lopez, Jeanne Oddoz, Fabienne Peira, Olivier Michel, Jérôme Meunier, Brahim Ouahrani, Antoine Roger, Sonia Branco, Van Nguyen, Mathilde Gisselbrecht, Ghania Hammad, Pierre Mordant, Magda Stroksztejn, Marc Pocard, Luc Nlo Meyengue, Emmanuelle Sacco, Sophie Simon Anne, Elizabeth Fabre-Guillevin, Marine Slim, Aziz Zaanan, Jacques Cadranel, Johan Pluvy, Rénata Ursu, Amyrath Geraldo, Rime Lihi, Maryline Vo, Zohra Brouk, Raphaël Colle, Mostefa Bennamoun, Fabrice Lacan, Christophe Louvet, Soraya Mebarki, Marianne Veyri, Elena Paillaud, Christelle Lucas, Olivier Dubreuil, Jamila Lyamani, Hanane Agguini, Emilie Soularue, Clément Jourdaine, Benjamin Verillaud, Hakima Herzine, Eric Raymond, Nathalie Mathiot, Lola Jade Palmieri, Christian Epanya, Julien Taieb, Eliane Bertrand, Gaël Goujon, Céline Namour, Benoit Gazeau, Biljana Zafirova, Haitham Mirghani, Catherine Belin, Kahina Belkhir, Myriam Gharib, Aurore Vozy, Karim Amrane, Jean-Philippe Spano, Johanna Wassermann, Loic Feuvret, Jean-Baptiste Bachet, Sara Philonenko, Laetitia Guillot, Marion Zabbe, Stéphanie Gibiat, Camille Baylot, Aude Jouinot, Nicolas Leduc, Sabine Vieillot, Laurie James, Camille Ducerf, Jean-Frédéric Blanc, Claire Falandry Leger, Virginie Wautot, Marion Chauvenet, Aude Vincent, David Tougeron, Sandrine Goulvent, Etienne Suc, Anne-Pascale Laurenty, Eric Marquis, Margaux Bonnaire, Maxime Dewolf, Esteban Brenet, Delphine Billard, Claude-Fabien Litre, Antoine Dumazet, Damien Botsen, Marion Vazel, Claire Carlier, David Bonnerave, Charles Marchand-Crety, Olivier Bouche, Patricia Fosse, David Sefrioui, Sarah Watson, Fatah Torche, Thierry Muron, Stéphane Natur, Romain Desgrippes, Véronique Bihel, François-Régis Ferrand, Caroline Leiterer, Julie Lavole, Claire Moquet, Nathalie Pressoir, Catherine Dziukala, Catherine Ligeza Poisson, Abdelhalim Naji, Nicolas Williet, Jean-Marc Phelip, Fabrice Di Palma, Amina Kherrour Mehdi, Julien Langrand-Escure, Pierre Fournel, Grégoire Pigne, Léa Saban-Roche, Nicolas Magne, Cécile Vassal, Jean-Philippe Jacquin, Carole Ramirez, Alexis Vallard, Olivier Collard, Romain Rivoirard, Ivan Graber, Stéphanie Trager Maury, Elodie Duboisset, Jorge Ayllon Ugarte, Dalilia Rami, Christine Saler, Manon Reinbolt, Clara Le Fevre, Meher Ben Abdelghani, Louis-Marie Dourthe, Joffrey Perruisseau-Carrier, Marlène Nguimpi-Tambou, Flavie Barret, Luisa Di Stefano Anna, Annie Balthazard, Camille Vassord-Dang, Mathilde Le Marchand, Julien Vergniol, Iulia Pripon, Axelle Daemaegdt, Vanessa Latry, Muna Larrieu, Gaëlle Landry, Laetitia Touihri Maximin, Francesco Del Piano, Agnès Barlet, Mylène Vernisse, Sophie Lafond, Charline Genin, Camille Sibertin-Blanc, Emilien Chabrillac, Caroline Gregoire, Sébastien Vergez, Quentin Panouille, Rosine Guimbaud, Floriane Richa, Loïc Lebellec, Sophie Gounin, Guillaume Buiret, Marine Baudin, Hervé Hamon, Anne-Claire Deshorgue, Eduardo Barrascout, Stéphanie Legrand, Morgane Houlze, Linda Cambula, Anthony Lopez, Guillaume Fouquet, Kahina Touabi, Adeline GermaIn, Benoit Godbert, Florence Voivret, Julie Perrin, Rosa Da Silva, Emilie Bernichon, GCO-002 CACOVID-19 collaborators/investigators, Moulin, S., Leleu, O., Leparree, S., Goasdoue, H., Piprot, C., Tourneur, G., Bayart, V., Lignier, D., Lachaier, E., Khamari, M., Coutte, A., Siembida, N., Houessinon, A., Regimbeau, J.M., Chauffert, B., Moreira, A., Hautefeuille, V., Hee, C., Boone, M., Bihan, C., Chive, E., Poulet-Potriquier, S., Fahem, R., Luet, D., Roquin, G., Vitellius, C., Cornet-Trichereau, N., Caroli-Bosc, F.X., Thirot-Bidault, A., Ropert, S., Gachet-Masson, J., Dehais, M., L'helgoualc'h, G.A., Ali-Mahamadou, I., Talfi, S., Belmont, L., Kilendo, D., Benrezzak, N., Dubief, E., Conroy, G., Delique, L., Basso, M., Pons, I., Salignon, K., Villing, A.L., Mougenot, E., Porebski, C., Guiatni, A., Cloarec, N., Mineur, L., Bouchaud, M., David, C., Peytier, A., Greletty, T., Audemar, F., Vignes, E., Minne, F., Goldzak, G., Huysman, F., Hocine, F., Lakkis, Z., Mansi, L., Meynard, G., Almotlak, H., Klajer, E., Sun, X.S., Wasselin, J., Catala, P., Mazuy, C., Vandamme, H., Prevost, J.B., Fadin, A., Basson, L., Huguet, J.B., Dos Santos, E., Jany, B., Saad, A., Goutorbe, F., Oziol, E., Ramdani, M., Kadiri, O., Garbay, D., Huet, C., Giroux Leprieur, E., Teng, W., Monvoisin, J., Arnaud Coffin, P., Roux, S., Orfeuvre, H., Chagros, M., Pillon, D., Rassoul, A., Poureau, P.G., Novello, C., Ducray, F., Trouba, C., Bastit, V., Babin, E., Thariat, J., Leon, V., Courtecuisse, A.C., Vambre, J., Tack, V., Desauw, C., Meniai, F., Peres, C., Esparcieux, A., Perrier, H., Doux, N., Kaphan, R., Roques, B., Rebischung, C., Mille, D., Fernandes, G., Abdelli, N., Jousset, N., Combe, P., Jonveaux, E., Dumont, P., Kanaan, M., Berthelot Gras, C., Panis, V., Kaluzinski, L., Venant-Valery, M., Lam, Y.H., Vallee, L., Riviere, F., Durand, M., Benghadid, D., Villeneuve, E., Hentic Dhome, O., Laurent, L., Bounouar, Z., De Mestier, L., Dubois, J., Eyriey, M., Moreau, L., Ahle, G., Baihas, D., Aldabbagh, K., Degriffolet, D., Sebbagh, V., Seghezzi, J.C., Lozach-Brugirard, M., Mandrou, J., Mavier, L., Hennetier, F., Wagner, J.P., Carola, E., Chandirakumaran, K., Loutski, S., Cojean-Zelek, I., Bouras, A., Lacour, S., Froura, F., Ben Nadji, H., Cattelain, S., Darloy, F., Jolimoy Boilleau, G., Maissiat, C., Darut-Jouve, A., Lorgis, V., Charifi-Alaoui, I., Ghiringhelli, F., Drouillard, A., Chaix, M., Manfredi, S., Lepage, C., Gagnaire, A., Latournerie, M., Jourdan, S., Perrot, N., Folia, M., Minello, A., Jouve, J.L., Fery, M., Landau, A., Evrard, D., Valenza, B., Paitel, J.F., Chablais, L., Kreitmann, T., Lancry-Lecomte, L., Monard, A., Faugeras, E., Boucheret, P., Glommeau, C., Tchikladze, C., Garnier Tixidre, C., Long, J., Zaidi, M., Delabarre, V., Meyzenc, J., Ferrand, L., Moro-Sibilot, D., Bouheret, P., Leyronnas, C., Herve, C., Thoor, A., Jacquet, E., Roth, G., Madapathage-Senanyake, V., Chupeau, P., Bieber, E., Rosso, M., Lepage, I., Priou, F., Laly, M., Aprelon, S., Sobolak, N., Homokos, H., Pointreau, Y., Watelle, F., Pham-Becker, A., Lauridant, G., Turpin, A., Dujardin, C., Lenglin, E., Nienguet Tsota, A., Dominguez, S., Forestier, A., Nouvel, F., Lerooy, J., Ratajczak, C., Romano, O., Brzyski, D., Barriere, A., Genet, D., Tisse, J., Zasadny, X., Grelet, A., Hennion-Imbault, A., Haustraete, E., Louafi, S., Awad, M., Zekri, Y., Cheneau, C., Leissen, N., Egreteau, J., Breant, A., Sarabi, M., Labonne, S., Forestier, J., Leclercq, C., Prunier-Bossion, F., Ray Coquard, I., Guillet, M., Theillaumas, A., Prome, E., Walter, T., Philouze, P., Lawo, M., De Talhouet, S., Beuvelot, J., Molin, Y., Bellecoste Martin, M., Saussereau, M., Agnelli, L., Fakhry, N., Laplace, C., Norguet Monnereau, E., Boucard, C., Djenad, K., Fontaine, C., Seitz, J.F., Dahan, L., Sigrand, J., Duluc, M., Locher, C., Fleury, M., Brou Marie, A., Berkane, R., Poupblanc, S., Auby, D., Petran, D., Texereau, P., Guerineau, E., Andre, M., Mahjoubi, L., Sarrazin, F., Jeanson, S., Gschwend, A., Birr, V., Debieuvre, D., Fore, M., Noirclerc, M., Dahou, S., Spaeth, D., Lambotin, M., Lelu, T., Linot, B., Hugon, N., Rousseau, D., Castanie, H., Lenne, C., Lortholary, A., Cessot, A., Merzoug, M., Naudin, C., Vannetzel, J.M., Aziz, G., Hadj Arab, Y., Pernes, S., Roche-Lachaise, I., Fiteni, F., Yahiaoui, H., Marel Lopez, G., Oddoz, J., Peira, F., Michel, O., Meunier, J., Ouahrani, B., Roger, A., Branco, S., Nguyen, V., Gisselbrecht, M., Hammad, G., Mordant, P., Stroksztejn, M., Pocard, M., Nlo Meyengue, L., Aparicio, T., Sacco, E., Simon Anne, S., Fabre-Guillevin, E., Wislez, M., Slim, M., Zaanan, A., Cadranel, J., Pluvy, J., Ursu, R., Geraldo, A., Lihi, R., Vo, M., Brouk, Z., Colle, R., Bennamoun, M., Lacan, F., Louvet, C., Mebarki, S., Veyri, M., Paillaud, E., Lucas, C., Dubreuil, O., Lyamani, J., Idbaih, A., Agguini, H., Soularue, E., Canellas, A., Zalcman, G., Jourdaine, C., Verillaud, B., Herzine, H., Raymond, E., Mathiot, N., Palmieri, L.J., Epanya, C., Taieb, J., Bertrand, E., Goujon, G., Namour, C., Gazeau, B., Zafirova, B., Mirghani, H., Belin, C., Belkhir, K., Gharib, M., Vozy, A., Amrane, K., Spano, J.P., Wassermann, J., Feuvret, L., Bachet, J.B., Philonenko, S., Guillot, L., Zabbe, M., Gibiat, S., Baylot, C., Jouinot, A., Leduc, N., Vieillot, S., James, L., Ducerf, C., Blanc, J.F., Falandry Leger, C., Wautot, V., Chauvenet, M., Vincent, A., Tougeron, D., Goulvent, S., Suc, E., Laurenty, A.P., Marquis, E., Bonnaire, M., Dewolf, M., Brenet, E., Billard, D., Litre, C.F., Dumazet, A., Botsen, D., Vazel, M., Carlier, C., Bonnerave, D., Marchand-Crety, C., Bouche, O., Fosse, P., Sefrioui, D., Michel, P., Watson, S., Neuzillet, C., Torche, F., Muron, T., Natur, S., Desgrippes, R., Bihel, V., Ferrand, F.R., Leiterer, C., Lavole, J., Moquet, C., Pressoir, N., Dziukala, C., Ligeza Poisson, C., Naji, A., Williet, N., Phelip, J.M., Di Palma, F., Kherrour Mehdi, A., Langrand-Escure, J., Fournel, P., Pigne, G., Saban-Roche, L., Magne, N., Vassal, C., Jacquin, J.P., Ramirez, C., Vallard, A., Collard, O., Rivoirard, R., Graber, I., Trager Maury, S., Duboisset, E., Ayllon Ugarte, J., Rami, D., Saler, C., Reinbolt, M., Le Fevre, C., Ben Abdelghani, M., Dourthe, L.M., Perruisseau-Carrier, J., Nguimpi-Tambou, M., Barret, F., Di Stefano Anna, L., Balthazard, A., Mabro, M., Vassord-Dang, C., Le Marchand, M., Vergniol, J., Pripon, I., Daemaegdt, A., Latry, V., Larrieu, M., Landry, G., Touihri Maximin, L., Del Piano, F., Barlet, A., Vernisse, M., Lafond, S., Genin, C., Sibertin-Blanc, C., Chabrillac, E., Gregoire, C., Vergez, S., Panouille, Q., Guimbaud, R., Richa, F., Lebellec, L., Gounin, S., Buiret, G., Baudin, M., Hamon, H., Deshorgue, A.C., Barrascout, E., Legrand, S., Houlze, M., Cambula, L., Lopez, A., Fouquet, G., Touabi, K., GermaIn, A., Godbert, B., Voivret, F., Perrin, J., Da Silva, R., Bernichon, E., Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), CH Colmar, Institut Curie [Paris], Centre Hospitalier Universitaire de Reims (CHU Reims), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Beaujon, Hôpital Foch [Suresnes], CHU Saint-Antoine [AP-HP], ARCAGY-GINECO, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut Gustave Roussy (IGR), Département de médecine nucléaire [Rennes], CRLCC Eugène Marquis (CRLCC), Département de médecine oncologique [Gustave Roussy], Département de cancérologie cervico-faciale [Gustave Roussy] (CCF), Centre Jean Bernard [Institut Inter-régional de Cancérologie - Le Mans], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hopital Saint-Louis [AP-HP] (AP-HP), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), AbbVie, Merck, Carthera, Transgene, Nutritheragene, Roche, Air Liquide, Eli Lilly Japan, LEO Pharma Research Foundation, Bayer, Novartis, Sanofi, Biogen, Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, Cancer Research, medicine.medical_treatment, Disease, law.invention, Cohort Studies, 0302 clinical medicine, Mechanical ventilation, Risk Factors, law, Neoplasms, Medicine, Prospective Studies, Prospective cohort study, Original Research, Cancer, Intensive care unit, 3. Good health, Death, Oncology, 030220 oncology & carcinogenesis, Female, France, Immunotherapy, Cohort study, medicine.medical_specialty, chemotherapy. radiotherapy, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Internal medicine, Humans, Chemotherapy, Mortality, Pandemics, Aged, Retrospective Studies, Radiotherapy, SARS-CoV-2, business.industry, COVID-19, Retrospective cohort study, Odds ratio, medicine.disease, Antineoplastic Agents/adverse effects, Antineoplastic Agents/therapeutic use, COVID-19/mortality, France/epidemiology, Neoplasms/mortality, Neoplasms/therapy, Neoplasms/virology, SARS-CoV-2/isolation & purification, 030104 developmental biology, business
Abstract: Background Cancer patients are thought to have an increased risk of developing severe Coronavirus Disease 2019 (COVID-19) infection and of dying from the disease. In this work, predictive factors for COVID-19 severity and mortality in cancer patients were investigated. Patients and Methods In this large nationwide retro-prospective cohort study, we collected data on patients with solid tumours and COVID-19 diagnosed between March 1 and June 11, 2020. The primary endpoint was all-cause mortality and COVID-19 severity, defined as admission to an intensive care unit (ICU) and/or mechanical ventilation and/or death, was one of the secondary endpoints. Results From April 4 to June 11, 2020, 1289 patients were analysed. The most frequent cancers were digestive and thoracic. Altogether, 424 (33%) patients had a severe form of COVID-19 and 370 (29%) patients died. In multivariate analysis, independent factors associated with death were male sex (odds ratio 1.73, 95%CI: 1.18-2.52), ECOG PS ≥ 2 (OR 3.23, 95%CI: 2.27-4.61), updated Charlson comorbidity index (OR 1.08, 95%CI: 1.01-1.16) and admission to ICU (OR 3.62, 95%CI 2.14-6.11). The same factors, age along with corticosteroids before COVID-19 diagnosis, and thoracic primary tumour site were independently associated with COVID-19 severity. None of the anticancer treatments administered within the previous 3 months had any effect on mortality or COVID-19 severity, except cytotoxic chemotherapy in the subgroup of patients with detectable SARS-CoV-2 by RT-PCR, which was associated with a slight increase of the risk of death (OR 1.53; 95%CI: 1.00-2.34; p = 0.05). A total of 431 (39%) patients had their systemic anticancer treatment interrupted or stopped following diagnosis of COVID-19. Conclusions Mortality and COVID-19 severity in cancer patients are high and are associated with general characteristics of patients. We found no deleterious effects of recent anticancer treatments, except for cytotoxic chemotherapy in the RT-PCR-confirmed subgroup of patients. In almost 40% of patients, the systemic anticancer therapy was interrupted or stopped after COVID-19 diagnosis., Highlights • A total of 1289 patients with solid tumours and COVID-19 were analysed. • Mortality and COVID-19 severity were mainly driven by patient general characteristics. • Overall, we found no deleterious effects of recent anticancer treatments on mortality. . • Systemic anticancer treatment was interrupted or stopped in 39% of patients.
Published: 2020
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15. Prognostic Value and Relation with Adjuvant Treatment Duration of ctDNA in Stage III Colon Cancer: a Post Hoc Analysis of the PRODIGE-GERCOR IDEA-France Trial

Author: Pierre Laurent-Puig, May Mabro, Valérie Taly, Jaafar Bennouna, Claire Mulot, Julie Henriques, Olivier Bouché, Jérôme Desramé, Joëlle Egreteau, Thibault Mazard, C. Lepere, Laurent Mineur, Christophe Louvet, Dewi Vernerey, Camille Bourreau, Kariman Chaba, Aimery de Gramont, Katia Hormigos, Julien Taieb, Thierry André, 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), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Cancer Research and Personalized Medicine - CARPEM [Paris], 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)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Saint-Jacques [CHRU de Besançon], Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut Sainte Catherine [Avignon], Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital privé Jean-Mermoz [Lyon] (Ramsay-GDS), Institut Mutualiste de Montsouris (IMM), Hôpital Foch [Suresnes], Groupe Hospitalier Bretagne Sud (GHBS), Hôpital Robert Debré, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut hospitalier Franco-Britannique [Levallois-Perret], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), TALY, Valerie, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: Cancer Research, medicine.medical_specialty, Colorectal cancer, medicine.medical_treatment, Treatment duration, [SDV]Life Sciences [q-bio], Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Post-hoc analysis, medicine, In patient, Stage (cooking), 030304 developmental biology, 0303 health sciences, business.industry, medicine.disease, 3. Good health, Stage III Colon Cancer, [SDV] Life Sciences [q-bio], Oncology, 030220 oncology & carcinogenesis, Baseline characteristics, business, Adjuvant
Abstract: Purpose:Circulating tumor DNA (ctDNA) has been suggested as a major prognostic factor in resected stage-III colon cancer. We analyzed ctDNA of patients randomized in the phase III IDEA-France trial.Experimental Design:ctDNA was tested for WIF1 and NPY by droplet digital PCR with method developed and validated for colorectal cancer. Disease-free survival (DFS) and overall survival (OS) were analyzed via multivariable analysis in patients with ctDNA samples and in sub-groups according to treatment duration (3/6 months) and disease stage (high/low-risk stage III).Results:Of 2,010 randomized patients, 1,345 had available ctDNA samples (1,017 collected both post-surgery and pre-chemotherapy). More Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 (78% versus 69%) and T4 and/or N2 (40% versus 36%) were observed in patients studied (n = 1017) versus not analyzed (n = 993). There were 877 ctDNA-negative (86.2%) and 140 ctDNA-positive (13.8%) patients; their baseline characteristics were similar. With a median follow-up of 6.6 years, the 3-year DFS rate was 66.39% for ctDNA-positive patients and 76.71% for ctDNA-negative patients (P = 0.015). ctDNA was confirmed as an independent prognostic marker for DFS (adjusted HR = 1.55, 95% CI 1.13–2.12, P = 0.006) and OS (HR = 1.65, 95% CI 1.12–2.43, P = 0.011). ctDNA was prognostic in patients treated for 3 months and with T4 and/or N2 tumors, but not in those treated for 6 months and with T1–3/N1 tumors.Conclusions:In this first ctDNA assessment of a large series of patients with stage III colon cancer enrolled in phase III trial, post-surgery ctDNA was found in 13.8% of them and was confirmed as an independent prognostic marker.See related commentary by Bent and Kopetz, p. 5449
Published: 2021
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16. 1032 Strong association between pathological response to neoadjuvant chemotherapy, TILs and modeled CA125 KELIM in ovarian carcinomas: CHIVA trial, GINECO

Author: S Moret, M. Leheurteur, Annick Chevalier-Place, L. Venat-Bouvet, Philippe Follana, Alexandra Leary, Jean-Pierre Lotz, Laure Favier, Sophie Abadie-Lacourtoisie, F Del Piano, Jérôme Meunier, C. Louvet, Benoit You, Anne Floquet, Olivier Colomban, G. De Rauglaudre, Pierre Combe, Carol Alliot, J Pierre-Alexandre, and N. Raban
Subjects: Oncology, medicine.medical_specialty, Chemotherapy, business.industry, Tumor-infiltrating lymphocytes, medicine.medical_treatment, Cancer, Immunotherapy, Debulking, medicine.disease, chemistry.chemical_compound, Isolated Tumor Cells, chemistry, Internal medicine, Ovarian carcinoma, medicine, Nintedanib, business
Abstract: Introduction/Background* As stated by ESGO-ESMO, there is a need for indicators of chemotherapy efficacy in ovarian carcinoma patients treated in first-line setting (Colombo et al, IGCS, 2020). The pathological chemotherapy response score (CRS) and the modeled CA-125 KELIM during neo-adjuvant chemotherapy were reported as potential markers. Moreover, changes in tumor infiltrating lymphocytes (TILs) after neo-adjuvant chemotherapy were reported as a prognostic factor (Leary et al, Cancer Immunol Immunother, 2021). We studied the relationships between changes in TILs, the pathological response (pR) and KELIM in patients treated with neo-adjuvant chemotherapy +/- interval debulking surgery (IDS) from CHIVA phase II trial. Methodology The patients were enrolled in the randomized phase II trial CHIVA (NCT01583322, neo-adjuvant carboplatin-paclitaxel +/- nintedanib, +/- IDS, n=188 patients). KELIM were previously calculated (You et al CCR 2020). The 30 patients with the highest KELIM (very chemosensitive) or the lowest KELIM (poorly chemosensitive) were selected. HE-stained sections from available tissue blocks at baseline and after chemotherapy were analyzed for stromal TILs (sTILs, surface of the tumor stroma occupied by lymphocytes) and intra-epithelial TILs (ieTILs, brisk or non-brisk). The pathological response (pR) was assessed on the most tumoral available tissue block obtained after chemotherapy (good response if extensive fibrous changes with no or isolated tumor cells, or Result(s)* No relationships between KELIM and TILs infiltrates on baseline tumor samples were found. However, strong associations were found between KELIM and TIL infiltrates after neo-adjuvant chemotherapy for sTILs (median KELIM for sTILs 0-5% vs >5%: 0.28 versus 1.32, P Conclusion* High consistency was found between the modeled CA125 KELIM calculated during the first 100 days of neo-adjuvant chemotherapy and the pathological response, consistent with their values as indicators of the tumor chemosensitivity in first-line setting. Moreover, TILs changes were strongly associated with chemosensitivity, opening hypotheses about the mechanisms of chemosensitivity, and immunotherapy opportunity.
Published: 2021
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17. Assessment of Coagulation by Thromboelastography During Ongoing Postpartum Hemorrhage

Author: A. Rigouzzo, Federica Piana, Nicolas Louvet, Nada Sabourdin, Rémi Favier, Isabelle Constant, Laure Girault, Marie-Virginie Ore, and M. Farrugia
Subjects: Adult, medicine.medical_specialty, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, 030202 anesthesiology, Internal medicine, Coagulopathy, medicine, Humans, Thrombus, Blood Coagulation, Coagulation Disorder, Retrospective Studies, Hemostasis, medicine.diagnostic_test, business.industry, Postpartum Hemorrhage, Area under the curve, Retrospective cohort study, Blood Coagulation Disorders, Hypofibrinogenemia, medicine.disease, Thromboelastography, Thrombelastography, Anesthesiology and Pain Medicine, Cardiology, Female, business, 030217 neurology & neurosurgery
Abstract: Rapid assessment of hemostasis during postpartum hemorrhage (PPH) is essential to allow characterization of coagulopathy, to estimate bleeding severity, and to improve outcome. Point of care (POC) coagulation monitors could be of great interest for early diagnosis and treatment of coagulation disorders in PPH.Women with ongoing PPH500 mL who clinically required an assessment of coagulation with thromboelastography (TEG) were included. The primary aim of this retrospective observational cohort study was to assess the predictive accuracy of TEG parameters for the diagnosis of coagulation disorders (hypofibrinogenemia ≤2 g/L, thrombocytopenia ≤80,000/mm, prothrombin ratio ≤50%, or activated partial thromboplastin time ratio ≥1.5) during PPH. The analyzed TEG parameters were Kaolin-maximum amplitude (K-MA), Kaolin-maximum rate of thrombus generation using G (K-MRTGG), functional fibrinogen-maximum amplitude (FF-MA), and functional fibrinogen-maximum rate of thrombus generation using G (FF-MRTGG). Secondary aims of this study were (1) comparison of the time delay between classical parameters and velocity curve-derived parameters (K-MA versus K-MRTGG and FF-MA versus FF-MRTGG) and (2) evaluation of the accuracy of TEG parameters to predict severe hemorrhage estimated by calculated blood losses.Ninety-eight patients were included with 98 simultaneous TEG analyses and laboratory assays. All parameters had an excellent predictive performance. For the Kaolin assay, no significant difference was evidenced between K-MA and K-MRTGG for the predictive performance for hypofibrinogenemia ≤2 g/L and/or thrombocytopenia ≤80,000/mm (respective area under the curve [AUC], 0.970 vs 0.981). For the functional fibrinogen assay, no significant difference was evidenced between FF-MA and FF-MRTGG for the predictive performance for hypofibrinogenemia ≤2 g/L (respective AUC, 0.988 vs 0.974). For both assays, the time to obtain results was shorter for the velocity parameters (K-MRTGG: 7.7 minutes [2.4 minutes] versus K-MA: 24.7 minutes [4.2 minutes], P.001; FF-MRTGG: 2.7 minutes [2.7 minutes] versus FF-MA: 14.0 minutes [4.3 minutes], P.001). All TEG parameters derived from the Kaolin and functional fibrinogen assays and Clauss fibrinogen were significantly predictive of severe PPH2500 mL.During PPH, when coagulation assessment is indicated, TEG provides a rapid and reliable detection of hypofibrinogenemia ≤2 g/L and/or thrombocytopenia ≤80,000/mm. No difference in performance was evidenced between the velocity-derived parameters (K-MRTGG and FF-MRTGG) and the classical parameters (K-MA and FF-MA). However, velocity-derived parameters offer the advantage of a shorter time to obtain results: FF-MRTGG parameter is available within ≤5 minutes. POC assessment of hemostasis during PPH management may help physicians to diagnose clotting disorders and to provide appropriate hemostatic support.
Published: 2020
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18. Carcinoembryonic Antigen Levels and Survival in Stage III Colon Cancer: Post hoc Analysis of the MOSAIC and PETACC-8 Trials

Author: Josep Tabernero, Edouard Auclin, Roger Faroux, Christophe Louvet, Aimery de Gramont, Jean-Luc Van Laethem, Côme Lepage, Maria Banzi, Magdalena Benetkiewicz, Gunnar Folprecht, Ramon Salazar, Thierry André, Julien Taieb, Thomas Aparicio, Enrico Mini, Dewi Vernerey, and Tamas Hickish
Subjects: 0301 basic medicine, medicine.medical_specialty, Epidemiology, Population, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Carcinoembryonic antigen, Risk groups, Internal medicine, Post-hoc analysis, Medicine, education, neoplasms, Survival analysis, education.field_of_study, biology, business.industry, digestive system diseases, Stage III Colon Cancer, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cohort, Restricted cubic splines, biology.protein, business
Abstract: Background: We explored and validated the association of postoperative carcinoembryonic antigen (CEA) with disease-free survival (DFS) and overall survival (OS) in stage III colon cancer. Methods: Patients with stage III colon cancer from the MOSAIC and PETACC-8 trials were enrolled. The relation between CEA and outcomes was continuously modeled with the restricted cubic splines (RCS) method. Association of CEA with outcomes was assessed by the Kaplan–Meier method, with two risk groups among patients with a CEA level ≤5 ng/mL. Multivariate Cox proportional hazard models were constructed. Results: The CEA level was available in 1,292 (96%) and 2,477 (97%) patients in the discovery and validation cohorts. The RCS analysis confirmed that patients with a CEA level >5 ng/mL were at highest risk of recurrence or death and those with a CEA level ≤5 ng/mL presented a heterogeneous risk population. In the discovery cohort, the 3-year DFS rate was 75%, 65%, and 45% in a group of patients with CEA level of 0–1.30 ng/mL (n = 630), 1.30–5 ng/mL (n = 613), and >5 ng/mL (n = 49), respectively (P < 0.001). CEA was independently associated with endpoints. All findings were confirmed in the validation cohort. Conclusions: Postoperative CEA level was highly and independently associated with DFS and OS, especially in patients with a CEA level of ≤5 ng/mL, suggesting that this cutoff is not optimal. Impact: CEA levels should be applied more accurately in future trials and clinical practice.
Published: 2019
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19. The prognostic impact of cirrhosis on patients receiving maintenance haemodialysis

Author: Sara Bellati, Justine Barthelon, Sébastien Dharancy, Guillaume Lassailly, Sebastien Gomis, Florent Artru, Philippe Mathurin, Marie Frimat, Alexandre Louvet, François Glowacki, Hélène Castel, Marc Hazzan, and Christian Noel
Subjects: Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, medicine.medical_treatment, Population, Severity of Illness Index, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Renal Dialysis, Internal medicine, Severity of illness, medicine, Clinical endpoint, Humans, Pharmacology (medical), 030212 general & internal medicine, Renal replacement therapy, education, Aged, Retrospective Studies, education.field_of_study, Hepatology, business.industry, Maintenance haemodialysis, Retrospective cohort study, Middle Aged, Prognosis, medicine.disease, Decompensated cirrhosis, Kidney Failure, Chronic, Female, 030211 gastroenterology & hepatology, business
Abstract: BACKGROUND Further study is needed on the prognostic impact of cirrhosis on haemodialysis patients. AIM To evaluate cirrhosis' impact according to severity on survival and to provide therapeutic guidelines for haemodialysis cirrhotic patients. METHODS Patients with end-stage renal failure treated with haemodialysis were included retrospectively from 01/01/2000 to 31/12/2004 and prospectively from 01/01/2005 to 31/12/2014 in our French Region. Clinical data, presence of cirrhosis and its severity were recorded at the beginning of haemodialysis. The primary endpoint was 2-year survival. RESULTS Seven thousand three hundred and fifty-four patients (96%) without cirrhosis and 304 patients (4%) with cirrhosis were included. Two-year survival in noncirrhotic patients was higher than in cirrhotic patients (71.7% vs 54.4%, P
Published: 2019
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20. Serum and Fecal Oxylipins in Patients with Alcohol-Related Liver Disease

Author: Samuel B. Ho, Yanhan Wang, Yi Duan, Alexandre Louvet, Peter Stärkel, Debbie L. Shawcross, Bei Gao, Philippe Mathurin, Sonja Lang, Bernd Schnabl, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, and UCL - (SLuc) Service de gastro-entérologie
Subjects: Adult, Male, Spectrometry, Mass, Electrospray Ionization, medicine.medical_specialty, Physiology, Alcoholic hepatitis, Gastroenterology, Article, Feces, Liver disease, Tandem Mass Spectrometry, Fatty Acids, Omega-6, Internal medicine, Fatty Acids, Omega-3, Humans, Metabolomics, Medicine, Oxylipins, Chromatography, High Pressure Liquid, Aged, Chromatography, Reverse-Phase, Hepatitis, Alcoholic, business.industry, Albumin, EPA, Middle Aged, Hepatology, Oxylipin, AA, medicine.disease, Eicosapentaenoic acid, DHA, Alcoholism, Lipid mediator, Docosahexaenoic acid, Female, Steatosis, business, PUFA, Biomarkers
Abstract: BACKGROUND: Alcohol-related liver disease is one of the most prevalent chronic liver diseases worldwide. Mechanisms involved in the pathogenesis of alcohol-related liver disease are not well understood. Oxylipins play a crucial role in numerous biological processes and pathological conditions. Nevertheless, oxylipins are not well studied in alcohol-related liver disease. AIMS: (1) To characterize the patterns of bioactive ω-3 and ω-6 polyunsaturated fatty acid metabolites in alcohol use disorder and alcoholic hepatitis patients, and (2) to identify associations of serum oxylipins with clinical parameters in patients with alcohol-related liver disease METHODS: We performed a comprehensive liquid chromatography with tandem mass spectrometry (LC-MS/MS)analysis of serum and fecal oxylipins derived from ω-6 arachidonic acid, ω-3 eicosapentaenoic acid and docosahexaenoic acid in a patient cohort with alcohol-related liver disease. RESULTS: Our results show profound alterations in the serum oxylipin profile of patients with alcohol use disorder and alcoholic hepatitis compared to non-alcoholic controls. Spearman correlation of the oxylipins with clinical parameters show a link between different serum oxylipins and intestinal permeability, aspartate aminotransferase, bilirubin, albumin, international normalized ratio, platelet count, steatosis, fibrosis and model for end-stage liver disease (MELD) score. Especially, higher level of serum 20- HETE was significantly associated with decreased albumin, increased hepatic steatosis, polymorphonuclear infiltration, and 90-day mortality. CONCLUSIONS: Patients with alcohol-related liver disease have different oxylipin profiles. Future studies are required to confirm oxylipins as disease biomarker or to connect oxylipins to disease pathogenesis.
Published: 2019
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21. Control of replication of hepatitis B and C virus improves patient and graft survival in kidney transplantation

Author: Marc Hazzan, Sébastien Dharancy, Christophe Legendre, Hélène Fontaine, Alain Duhamel, Nassim Kamar, Benjamin Legendre, Stanislas Pol, Corinne Antoine, Philippe Mathurin, Alexandre Louvet, Laurent Alric, Julien Labreuche, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Unité de biostatistiques, CRLCC Val d'Aurelle - Paul Lamarque, Physiopathologie des Maladies Inflammatoires de l'Intestin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Service des Maladies de l'Appareil Digestif et de la Nutrition [CHRU Lille], Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Agence de la biomédecine [Saint-Denis la Plaine], Service Néphrologie et transplantation rénale Adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie et Transplantation rénale [CHRU-lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Néphrologie - Immunologie Clinique [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-PRES Université de Toulouse, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Unité fonctionnelle d’éthique et médecine légale [AP-HP Hôpital Necker Enfants malades], Hôpital Purpan [Toulouse], and CHU Toulouse [Toulouse]
Subjects: Male, 0301 basic medicine, MESH: Antiviral Agents / therapeutic use, Kidney transplant recipients, [SDV]Life Sciences [q-bio], MESH: Hepatitis B, Chronic / virology, Hepacivirus, Virus Replication, medicine.disease_cause, Gastroenterology, 0302 clinical medicine, Interferon, MESH: Hepatitis C, Chronic / virology, Kidney transplantation, Graft Survival, MESH: Hepatitis B virus / drug effects, virus diseases, Middle Aged, MESH: Kidney Transplantation / mortality, Hepatitis B, Prognosis, MESH: Case-Control Studies, MESH: Hepatitis C, Chronic / drug therapy, 3. Good health, MESH: Hepacivirus / drug effects, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, 030211 gastroenterology & hepatology, medicine.drug, Adult, Hepatitis B virus, medicine.medical_specialty, MESH: Graft Survival, Hepatitis C virus, Antiviral Agents, Virus, 03 medical and health sciences, Hepatitis B, Chronic, MESH: Hepacivirus / physiology, Internal medicine, medicine, Humans, chronic hepatitis C, chronic hepatitis B, Hepatitis, Hepatology, business.industry, MESH: Adult, MESH: Hepatitis B virus / physiology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatitis C, Chronic, medicine.disease, Kidney Transplantation, 030104 developmental biology, MESH: Virus Replication / drug effects, Viral replication, Case-Control Studies, business, MESH: Female, MESH: Hepatitis B, Chronic / drug therapy
Abstract: International audience; Background & aims: Before antiviral therapy, kidney transplant recipients infected with hepatitis B virus (HBV) or hepatitis C virus (HCV) had poor outcomes. Since the 90s, nucleos(t)ide analogues have been widely used in HBV-infected patients, while interferon-based therapy was rarely used in HCV-infected patients. The aim of this study was to assess the impact of HBV and HCV on patient and graft survival, according to viral replication status.Methods: Data from January 1993 to December 2010 were extracted from the French national database CRISTAL. A total of 31,433 kidney transplant recipients were included, of whom 575, 1,060 and 29,798 had chronic hepatitis B, C, or were not infected, respectively.Results: Ten-year survival was lower in HCV-infected (71.3%) than in HBV-infected (81.2%, p = 0.0004) or non-infected kidney transplant recipients (82.7%, p
Published: 2019
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22. Successful treatment with yttrium-90 microspheres in a metastatic breast cancer patient and sclerosing cholangitis

Author: Cedric Van Marcke, Philippe D'Abadie, Emmanuel Seront, Aurélie Louvet, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Service de médecine nucléaire, UCL - (SLuc) Unité d'oncologie médicale, and UCL - (SLuc) Centre de malformations vasculaires congénitales
Subjects: Oncology, Curative intent, medicine.medical_specialty, business.industry, Case Report, trans-arterial radioembolization, Malignancy, medicine.disease, Metastatic breast cancer, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, breast cancer, 0302 clinical medicine, Breast cancer, 030220 oncology & carcinogenesis, Internal medicine, Localized disease, Yttrium-90 microspheres, yttrium-90, medicine, business, liver metastases, metastasis-directed therapies, Biotechnology
Abstract: Breast cancer is the most common malignancy occurring in women worldwide. More than 90% of patients present with localized disease are treated with curative intent; however, recurrence can occur with development of metastatic lesions. Frequently associated with extra-hepatic lesions, localized treatments (surgery or stereotaxic body radiotherapy) are rarely proposed in liver lesions. 90Y radioembolization has extensively been evaluated in colorectal cancer, but its role in breast cancer with isolated liver metastases remains largely unknown. Pre-existing liver diseases are known risk factors for 90Y induced liver toxicity. Not considered as an excluding factor for this treatment, data are limited regarding its safe use with cholangitis. We report a successful control of liver metastases by 90Y radioembolization in a breast cancer patient., Lay abstract Breast cancer is the most common malignancy occurring in women worldwide. Metastasis-directed therapies are more and more often offered to patients in order to delay systemic treatments; however, their role in improving survival remains unknown. Trans-arterial radioembolization with 90Y appears to be an interesting strategy in breast cancer with isolated liver metastases, even if its survival benefit remains largely unknown. Safety of trans-arterial radioembolization also remains under investigated in patients with previous liver disease. We report a successful control of liver metastases by 90Y radioembolization in a breast cancer patient.
Published: 2021
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23. Vaccination contre la COVID-19 des patients atteints de cancer solide : revue et préconisations d’un inter-groupe oncologique français (CGO, TNCD, UNICANCER)

Author: Khê Hoang Xuan, Juliette Thariat, Jean Bourhis, Florence Huguet, David Tougeron, Jean-Yves Blay, Thomas Aparicio, Philippe Gorphe, Pierre Michel, Sébastien Gaujoux, Pascale Mariani, Amélie Servettaz, Michel Ducreux, Christophe Louvet, Olivier Bouché, Barbara Seitz-Polski, Thierry Lecomte, Boris Guiu, Astrid Lièvre, Anne-Claire Hardy-Bessard, Maxime Hentzien, Léon Maggiori, Firouzé Bani-Sadr, Virginie Westeel, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), UNICANCER, Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de cancérologie cervico-faciale [Gustave Roussy] (CCF), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Universitaire de Cancérologie [Sorbonne Université] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Cooperator Multidisciplinary Oncology Group (GERCOR), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Curie [Paris], Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Léon Bérard [Lyon], Aucun, Hôpital Lapeyronie [Montpellier] (CHU), Institut Universitaire de Cancérologie [Paris] (IUC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, 2019-20 coronavirus outbreak, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV.CAN]Life Sciences [q-bio]/Cancer, Immunotherapy, Adoptive, 03 medical and health sciences, Cancers solides, 0302 clinical medicine, Neoplasms, medicine, Humans, Chemotherapy, Radiology, Nuclear Medicine and imaging, Molecular Targeted Therapy, Pandemics, Radiothérapie, Gynecology, Radiotherapy, business.industry, Contraindications, Vaccination, Synthèse, Neoplasms therapy, COVID-19, Hematology, General Medicine, 3. Good health, Coronavirus, 030104 developmental biology, Solid cancers, Oncology, 030220 oncology & carcinogenesis, France, business, Chimiothérapie
Abstract: La pandémie COVID-19 a un impact majeur à toutes les étapes de prise en charge des cancers. Le risque de décès de la COVID-19 chez les patients traités pour un cancer est élevé. La vaccination contre la COVID-19 représente une opportunité majeure pour réduire les risques de formes graves de la maladie et maintenir une filière de soins oncologiques normale. La définition de la population à vacciner est complexe, avec des données scientifiques très limitées et un contexte de pénurie en vaccin. Il apparaît théoriquement important de vacciner les patients atteints de cancers en cours de traitement ou avec un traitement datant de moins de trois ans, ainsi que leur entourage. Les patients actuellement prioritaires dits « à haut risque » sont ceux atteints de cancers en cours de chimiothérapie. Un groupe d’experts a préconisé une population « ultra-prioritaire » différente, incluant les patients sous chimiothérapie à visée curative ou palliative de première ou deuxième ligne, mais aussi ceux traités par chirurgie ou radiothérapie avec un grand volume pulmonaire, ganglionnaires et/ou de tissus hématopoïétiques. La vaccination doit idéalement être réalisée avant le début des soins. Malgré l’absence de données publiées, elle peut aussi s’effectuer pendant une chimiothérapie en évitant les périodes d’aplasie, avec possibilité de vacciner dans les établissements de soins. La mise en place de cohortes avec suivi immunologique et clinique des patients vaccinés atteints de cancer est nécessaire. Dans l’état actuel des connaissances, le rapport bénéfice/risque est très en faveur de la vaccination de tous les patients atteints de cancers.
Published: 2021
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24. To buy or not to buy-evaluating commercial AI solutions in radiology (the ECLAIR guidelines)

Author: Charles E. Kahn, Antoine Tournier, Patrick Omoumi, Tobias Kober, Alexis Ducarouge, Fanny Louvet-de Verchère, Jonas Richiardi, Hugh Harvey, and Daniel Pinto dos Santos
Subjects: Diagnostic Imaging, Artificial intelligence, medicine.medical_specialty, Legislation, Workload, Artificial Intelligence, Humans, Radiography, Radiology, Software, Equipment and supplies, Medicine, Radiology, Nuclear Medicine and imaging, Relevance (information retrieval), Point (typography), business.industry, Stakeholder, Usability, General Medicine, Imaging Informatics and Artificial Intelligence, Work (electrical), Available for sale, business
Abstract: Abstract Artificial intelligence (AI) has made impressive progress over the past few years, including many applications in medical imaging. Numerous commercial solutions based on AI techniques are now available for sale, forcing radiology practices to learn how to properly assess these tools. While several guidelines describing good practices for conducting and reporting AI-based research in medicine and radiology have been published, fewer efforts have focused on recommendations addressing the key questions to consider when critically assessing AI solutions before purchase. Commercial AI solutions are typically complicated software products, for the evaluation of which many factors are to be considered. In this work, authors from academia and industry have joined efforts to propose a practical framework that will help stakeholders evaluate commercial AI solutions in radiology (the ECLAIR guidelines) and reach an informed decision. Topics to consider in the evaluation include the relevance of the solution from the point of view of each stakeholder, issues regarding performance and validation, usability and integration, regulatory and legal aspects, and financial and support services. Key Points • Numerous commercial solutions based on artificial intelligence techniques are now available for sale, and radiology practices have to learn how to properly assess these tools. • We propose a framework focusing on practical points to consider when assessing an AI solution in medical imaging, allowing all stakeholders to conduct relevant discussions with manufacturers and reach an informed decision as to whether to purchase an AI commercial solution for imaging applications. • Topics to consider in the evaluation include the relevance of the solution from the point of view of each stakeholder, issues regarding performance and validation, usability and integration, regulatory and legal aspects, and financial and support services.
Published: 2021

25. Autochthonous hepatitis E as a cause of acute-on-chronic liver failure and death: histopathology can be misleading but transaminases may provide a clue

Author: Florent Artru, Christine Sempoux, Achim Weber, Jörg Neuweiler, Magdalena Filipowicz Sinnreich, Alexandre Louvet, Gieri Cathomas, Darius Moradpour, Felix Brunner, Matteo Montani, David Semela, Beat Müllhaupt, Daniela Lenggenhager, Jérôme Gouttenoire, Montserrat Fraga, Joana Vieira Barbosa, Philippe Mathurin, and University of Zurich
Subjects: Male, medicine.medical_specialty, Cirrhosis, Alcoholic hepatitis, 610 Medicine & health, 2700 General Medicine, Gastroenterology, chemistry.chemical_compound, Internal medicine, 10049 Institute of Pathology and Molecular Pathology, medicine, Hepatitis E virus, Humans, Decompensation, Transaminases, Aged, business.industry, Ribavirin, Acute-On-Chronic Liver Failure, General Medicine, Middle Aged, medicine.disease, Hepatitis E, 10219 Clinic for Gastroenterology and Hepatology, chemistry, Case-Control Studies, Liver function, Steatohepatitis, business, Viral hepatitis
Abstract: BACKGROUND AND AIM Acute decompensation and death have been observed in patients with acute hepatitis E virus (HEV) infection and preexisting liver cirrhosis. However, the clinical, laboratory and histological features need to be fully characterised. METHODS Some of us recently described the histological presentation of hepatitis E in a large panel of liver tissue specimens. Here, we conducted a case-control study to investigate the clinical and laboratory features of the subset of patients with HEV-related acute-on-chronic liver failure (ACLF) and death. Each patient was matched to three control patients with histologically confirmed severe alcoholic hepatitis based on sex, age, total bilirubin, INR, serum creatinine and MELD score on admission. RESULTS Of 5 patients who died in a context of HEV-related ACLF, 3 (60%) were male and the median age was 66 years (range 51–76). Median alanine aminotransferase (ALT) at presentation was 2610 U/l (range 705–3134) and aspartate aminotransferase (AST) 2818 U/l (range 1176–8611). Liver function was heavily altered in all patients. Histological analyses revealed steatohepatitis on a background of cirrhosis, suggestive of an alcoholic or nonalcoholic origin. Based on histopathology, alcoholic hepatitis was initially suspected in two patients and corticosteroid treatment was initiated. Ribavirin was started in four patients. Median time from hospitalisation to death was 17 days (range 6–25 days). AST levels in patients with HEV-related ACLF were significantly higher as compared to the matched patients with severe alcoholic hepatitis. CONCLUSION Typical histopathological features of viral hepatitis may be absent in ACLF caused by HEV infection. HEV infection should be sought in acute decompensation of cirrhosis and ACLF even in the absence of histological changes suggesting viral infection.
Published: 2021
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26. The Level of Alcohol Consumption in the Prior Year Does Not Impact Clinical Outcomes in Patients With Alcohol-Associated Hepatitis

Author: José Altamirano, Francisco Bosques-Padilla, Ramon Bataller, Debbie L. Shawcross, Michael R. Lucey, Jessica Musto, Robert S. Brown, Philippe Mathurin, Elizabeth C. Verna, Bernd Schnabl, Guadalupe Garcia-Tsao, Juan Caballería, Alexandre Louvet, Jens C. Eickhoff, Meritxell Ventura-Cots, Victor Vargas, and Juan G. Abraldes
Subjects: Adult, Male, medicine.medical_specialty, Alcohol Drinking, medicine.medical_treatment, Alcoholic hepatitis, Alcohol abuse, Alcohol use disorder, Liver transplantation, Severity of Illness Index, End Stage Liver Disease, Liver disease, health services administration, Internal medicine, medicine, Humans, Prospective Studies, Driving under the influence, Aged, Hepatitis, Transplantation, Alcohol Use Disorders Identification Test, Hepatology, business.industry, Hepatitis, Alcoholic, celebrities, Middle Aged, medicine.disease, Prognosis, Liver Transplantation, celebrities.reason_for_arrest, Alcoholism, Surgery, Female, business
Abstract: The 10-item Alcohol Use Disorders Identification Test (AUDIT-10) and its shorter form, AUDIT-Consumption (AUDIT-C), are questionnaires used to characterize severity of drinking. We hypothesized that liver injury and short-term outcomes of alcohol-associated hepatitis (AH) would correlate with a patient's recent alcohol consumption as determined by AUDIT-10 and AUDIT-C. We analyzed a prospective international database of patients with AH diagnosed based on the National Institute on Alcohol Abuse and Alcoholism (NIAAA) standard definitions. All patients were interviewed using AUDIT-10. Primary outcomes included the discriminatory ability of the AUDIT-10 and AUDIT-C scores for predicting survival status at 28 and 90 days and severity of liver injury, as measured by Model for End-Stage Liver Disease-sodium (MELD-Na). The relationship between AUDIT scores and survival status was quantified by calculating the area under the curve of the receiver operating characteristic analysis. The relationship between AUDIT scores and MELD-Na was examined using correlation coefficients. In 245 patients (age range 25-75 years; 35% female), we found no correlation between AUDIT-10 or AUDIT-C scores and either 28- or 90-day mortality. Similarly, there was no correlation between AUDIT-10 and AUDIT-C and MELD-Na scores. There was a strong positive correlation between MELD-Na and 28- and 90-day mortality. Additional measures of severity of alcohol use (average grams of alcohol consumed per day, years of drinking, convictions for driving under the influence, and rehabilitation attempts) and psychosocial factors (marriage, paid employment, and level of social support) had no influence on MELD-Na. In patients presenting with AH, AUDIT-10 and AUDIT-C were predictors of neither clinical severity of liver disease nor short-term mortality, suggesting that level of alcohol consumption in the prior year is not key to the presenting features or outcome of AH.
Published: 2021

27. Impact of cirrhosis aetiology on incidence and prognosis of hepatocellular carcinoma diagnosed during surveillance

Author: Nathalie Ganne-Carrié, Pierre Nahon, Cendrine Chaffaut, Gisèle N’Kontchou, Richard Layese, Etienne Audureau, Sylvie Chevret, Isabelle Archambeaud, Louis d’Alteroche, Frédéric Oberti, Dominique Roulot, Christophe Moreno, Alexandre Louvet, Thông Dao, Romain Moirand, Odile Goria, Eric Nguyen-Khac, Nicolas Carbonell, Jean-Charles Duclos-Vallée, Stanislas Pol, Victor de Ledinghen, Violaine Ozenne, Jean Henrion, Jean-Marie Péron, Albert Tran, Gabriel Perlemuter, Xavier Amiot, Jean-Pierre Zarski, Tarik Asselah, Dominique Guyader, Hélène Fontaine, Georges-Philippe Pageaux, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Jean-Pierre Bronowicki, Thomas Decaens, Ghassan Riachi, Paul Calès, Laurent Alric, Marc Bourlière, Philippe Mathurin, Sebastien Dharancy, Jean-Frédéric Blanc, Armand Abergel, Olivier Chazouillères, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Claire Wartelle, Dominique Thabut, Christophe Pilette, Christine Silvain, Christos Christidis, Brigitte Bernard-Chabert, Sophie Hillaire, Vincent Di Martino, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Nord, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), 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 Paris Cité (UPCité), Hôpital Henri Mondor, Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), ANRS CO12 CirVir group: Pierre Nahon1, Tarik Asselah2, Dominique Guyader3, Stanislas Pol4, Hélène Fontaine4, Georges-Philippe Pageaux5, Victor De Lédinghen6, Denis Ouzan7, Fabien Zoulim8, Dominique Roulot9, Albert Tran10, Jean-Pierre Bronowicki11, Thomas Decaens12, Ghassan Riachi13, Paul Calès14, Jean-Marie Péron15, Laurent Alric16, Marc Bourlière17, Philippe Mathurin18, Sebastien Dharancy18, Jean-Frédéric Blanc19, Armand Abergel20, Olivier Chazouillères21, Ariane Mallat22, Jean-Didier Grangé23, Pierre Attali24, Louis d’Alteroche25, Claire Wartelle26, Thông Dao27, Dominique Thabut28, Christophe Pilette29, Christine Silvain30, Christos Christidis31, Eric Nguyen-Khac32, Brigitte Bernard-Chabert 33, Sophie Hillaire34, Vincent Di Martino35. 1AP-HP, Hôpital Avicenne, Service d’Hépatologie, Bobigny, Université Sorbonne Paris Nord, Bobigny et INSERM U1138, Université de Paris, 2AP-HP, Hôpital Beaujon, Service d’Hépatologie, and University Paris Diderot, Sorbonne Paris Cité, CRI, UMR 1149, 3CHU Pontchaillou, Service d’Hépatologie, Rennes, 4AP-HP, Hôpital Cochin, Département d’Hépatologie et INSERM UMS20 et U1223, Institut Pasteur, Université Paris Descartes, Paris, 5Hôpital Saint Eloi, Service d’Hépatologie, Montpellier, 6Hôpital Haut-Lévêque, Service d’Hépatologie, Bordeaux, 7Institut Arnaud Tzanck, Service d’Hépatologie, St Laurent du Var, 8Hôpital Hôtel Dieu, Service d’Hépatologie, Lyon, 9AP-HP, Hôpital Avicenne, Service de Medeine Interne, Bobigny, 10CHU de Nice, Service d’Hépatologie, et INSERM U1065, Université de Nice-Sophia-Antipolis, Nice, 11Hôpital Brabois, Service d’Hépatologie, Vandoeuvre-les-Nancy, 12Hôpital Michallon, Service d’Hépatologie, Grenoble, 13Hôpital Charles-Nicolle, Service d’Hépatologie, Rouen, 14CHU d’Angers, Service d’Hépatologie, Angers, 15Hôpital Purpan, Service d’Hépatologie, Toulouse, 16CHU Toulouse, Service de Médecine Interne-Pôle Digestif UMR 152, Toulouse, 17Hôpital Saint Joseph, Service d’Hépatologie, Marseille, 18Hôpital Claude Huriez, Service d’Hépatologie, Lille, 19Hôpital St André, Service d’Hépatologie, Bordeaux, 20Hôpital Hôtel Dieu, Service d’Hépatologie, Clermont-Ferrand, 21AP-HP, Hôpital Saint-Antoine, Service d’Hépatologie, Paris, 22AP-HP, Hôpital Henri Mondor, Service d’Hépatologie, Créteil, 23AP-HP, Hôpital Tenon, Service d’Hépatologie, Paris, 24AP-HP, Hôpital Paul Brousse, Service d’Hépatologie, Villejuif, 25Hôpital Trousseau, Unité d’Hépatologie, CHRU de Tours, 26Hôpital d’Aix-En-Provence, Service d’Hépatologie, Aix-En-Provence, 27Hôpital de la Côte de Nacre, Service d’Hépatologie, Caen, 28AP-HP, Groupe Hospitalier de La Pitié-Salpêtrière, Service d’Hépatologie, Paris, 29CHU Le Mans, Service d’Hépatologie, Le Mans, 30CHU de Poitiers, Service d’Hépatologie, Poitiers, 31Institut Mutualiste Montsouris, Service d’Hépatologie, Paris, 32Hôpital Amiens Nord, Service d’Hépatologie, Amiens, 33Hôpital Robert Debré, Service d’Hépatologie, Reims, 34Hôpital Foch, Service d’Hépatologie, Suresnes, 35Hôpital Jean Minjoz, Service d’Hépatologie, Besançon. France., CIRRAL group: Nathalie Ganne-Carrié1, Cendrine Chaffaut2, Isabelle Archambeaud3, Louis d’Alteroche4, Frédéric Oberti5, Dominique Roulot6, Christophe Moreno7, Alexandre Louvet8, Thông Dao9, Romain Moirand10, Odile Goria11, Eric Nguyen-Khac12, Nicolas Carbonell13, Jean-Charles Duclos-Vallée14, Stanislas Pol15,16, Victor de Ledinghen17, Violaine Ozenne18, Jean Henrion19, Jean-Marie Péron20, Albert Tran21,22, Gabriel Perlemuter23, Xavier Amiot24, Jean-Pierre Zarski25, Sylvie Chevret2. 1AP-HP, Hôpital Avicenne, Service d’Hépatologie, Bobigny, Université Sorbonne Paris Nord, Bobigny et INSERM U1138, Université de Paris, 2SBIM, APHP, Hôpital Saint-Louis, Paris, Inserm, UMR-1153, ECSTRA Team, Paris, France, 3Liver, CHU, Nantes, France, 4Liver Unit, University Hospital, Tours, France, 5Liver Unit, University Hospital, Angers, France, 6AP-HP, Hôpital Avicenne, Service de Médecine Interne, Bobigny, Université Sorbonne Paris Nord, Bobigny, 7Liver unit, CUB Hôpital Erasme, Université Libre de Bruxelles, Belgium, 8Liver Unit, University Hospital, Lille, France, 9Liver Unit, University Hospital, Caen, France, 10Liver Unit, University Hospital, Rennes, France, 11Liver Unit, University Hospital, Rouen, France, 12Liver Unit, University Hospital, Amiens, France, 13 Liver Unit, APHP, CHU Saint-Antoine, Paris, France, 14Liver Unit, APHP, CHU Paul Brousse, Villejuif, France, 15Université Paris Descartes, APHP, Liver Unit, Hôpital Cochin, 16INSERM U1223, Institut Pasteur, Paris, France, 17Hepatology Unit, University Hospital, CHU Bordeaux, France, 18Liver Unit, APHP, CHU Lariboisière, Paris, France, 19Liver Unit, University Hospital, Haine Saint-Paul, Belgium, 20Liver Unit, Universitary Hospital Purpan, University Paul Sabatier III, Toulouse, 21Institut National de la Santé et de la Recherche Médicale (INSERM), U1065, Team 8, 'Hepatic Complications in Obesity', Nice, F-06204, Cedex 3, France, 22University Hospital of Nice, Digestive Centre, Nice, F-06202, Cedex 3, France, 23Liver Unit, University Hospital, Béclère, APHP, Clamart, France, 24Liver Unit, APHP, CHU Tenon, Paris, France, and 25Clinique d’hépato-gastroentérologie pôle Digidune CHU de Grenoble, France
Subjects: Alcoholic liver disease, medicine.medical_specialty, Cirrhosis, primary liver cancer, VIR, virus-related, ECOG Performance Status, [SDV.CAN]Life Sciences [q-bio]/Cancer, MIX, alcohol and virus-related, RC799-869, Gastroenterology, law.invention, Randomized controlled trial, law, Internal medicine, Internal Medicine, medicine, Immunology and Allergy, Hepatology, business.industry, Incidence (epidemiology), cirrhosis, competing risk analysis, US, abdominal ultrasound, Hazard ratio, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Diseases of the digestive system. Gastroenterology, medicine.disease, HR, hazard ratio, Hepatocellular carcinoma, ALC, alcohol-related, Etiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, HCC, hepatocellular carcinoma, Research Article, alcoholic liver disease
Abstract: Background & Aims In this study we aimed to analyse the impact of the aetiology of cirrhosis on the incidence, characteristics and prognosis of hepatocellular carcinoma (HCC) diagnosed during a surveillance program. Methods Individual data from a randomized trial and 2 prospective cohorts of patients with compensated histologically proven cirrhosis recruited between 2000 and 2016 were pooled. The influence of cirrhosis aetiology on survival after HCC detection was assessed using multivariable regression models. Results Among 3,533 patients (1,926 virus [VIR], 1,167 alcohol [ALC], 440 combined [MIX]), 431 were diagnosed with HCC after a median follow-up of 57.1 months. The 5-year HCC incidence was lowest in ALC (VIR 12.6%, ALC 9.1%, MIX 14.3%, p = 0.04). At the time of diagnosis, tumour burden and Child-Pugh score were comparable across aetiology groups, but early BCLC stages (0/A) were significantly less frequent in ALC (VIR 80%, ALC 37%, MIX 72%) as a result of worse ECOG performance status. However, similar access to first-line curative HCC treatment was reported across aetiology groups (p = 0.68). Median survival after HCC diagnosis was significantly reduced in ALC (VIR 39, ALC 21, MIX 34 months, p = 0.02). However, when adjusting for tumour size, ECOG and Child-Pugh score, the aetiology of the underlying cirrhosis no longer had a significant impact. Conclusion Compared to patients with virus-related cirrhosis, patients with alcohol-related compensated cirrhosis enrolled in a surveillance program have: i) the lowest 5-year HCC incidence; ii) worse overall prognosis, mostly driven by a poor general condition, despite similar access to first-line curative treatment. Lay summary It has been suggested that early detection of hepatocellular carcinoma (HCC) may be futile in patients with alcohol-related cirrhosis. By comparing outcomes in more than 3,000 patients with compensated cirrhosis included in surveillance programs, this study suggests that HCC surveillance enables early diagnosis in most patients with alcohol-related cirrhosis despite a higher competing risk of death in these patients. We also report similar access to first-line curative HCC treatment in these patients compared to those with viral cirrhosis, despite higher rates of comorbidities and impaired liver function. Following HCC detection, the later parameters were major drivers of death irrespective of the cause of cirrhosis. Registration CHC2000 (NCT00190385) and CIRRAL (NCT01213927) cohorts were registered at ClinicalTrials.gov and the full protocols are available at the following links (https://clinicaltrials.gov/ct2/show/NCT00190385) and https://clinicaltrials.gov/ct2/show/NCT01213927, respectively). The full CirVir protocol is available via the ANRS Web site (http://anrs.fr)., Graphical abstract, Highlights • Alcohol-related cirrhosis linked to the lowest incidence of HCC, the lowest overall survival and the highest incidence of decompensation. • Alcohol-related cirrhosis linked to fewer cases of early stage HCC, although tumour burden and Child-Pugh score were comparable across groups. • Patients with alcohol-related cirrhosis had worse survival after HCC diagnosis than those with virus-related cirrhosis. • The aetiology of cirrhosis had no impact on survival after HCC diagnosis following adjustment for other potential prognostic factors.
Published: 2021
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28. 1854P Multicentric, comparative, retrospective study on the safety and efficacy of conventional chemotherapy in cirrhotic patients with gastrointestinal cancer

Author: J. Wasselin, Anne Ploquin, M. Bertez, Alexandre Louvet, Stéphane Cattan, Philippe Mathurin, Nicolas Bertrand, H. Lubret, Guillaume Lassailly, H. Vandamme, C. Cheymol, Valérie Canva, Sébastien Dharancy, C. Desauw, Stéphanie Truant, Massih Ningarhari, P. Catala, and Anthony Turpin
Subjects: medicine.medical_specialty, Oncology, business.industry, Internal medicine, medicine, Conventional chemotherapy, Retrospective cohort study, Hematology, Gastrointestinal cancer, business, medicine.disease
Published: 2021
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29. Identification of optimal therapeutic window for steroid use in severe alcohol-associated hepatitis: A worldwide study

Author: Gustavo Romero, Pierre-Emmanuel Rautou, Saba Abdulsada, Kristina R. Chacko, Roberta Chaves Araújo, Won Kim, Rohit Agrawal, Germán Soriano, Juan Pablo Arab, Inés García-Carrera, Wei Zhang, Juan Pablo Arancibia, Seth Buryska, Andreea Bumbu, Richard D. Parker, Diego Rincón, Pamela Yaquich, Alexandre Louvet, Douglas A. Simonetto, Aldo Torre, Patrick S. Kamath, Tazime Issoufaly, Susana Castro-Sanchez, Felipe Zamarripa, Juan Pablo Roblero, Manuel Mendizabal, Vijay H. Shah, Zohaib Syed Haque, Fernando Bessone, Tej I Mehta, Julio Santiago Marcelo, Ramon Bataller, Carolina A. Ramírez, Tehseen Haider, Muhammad Majeed, Virginia Clark, Veronica Prado, Natalia Baeza, Natalia Bystrianska, Prasun K. Jalal, Rakhi Maiwall, Elizabeth C. Verna, Horia Stefanescu, Michael R. Lucey, Philippe Mathurin, Patricia Guerra Salazar, Berta Cuyàs, Ana Clemente-Sanchez, Maria Laura Garrido, Maria A. Poca, Adelina Horhat, A. Rojo, Luis G. Toro, Luis Antonio Díaz, Juan Carlos Restrepo, Francisco Idalsoaga, Lubomir Skladaný, Dalia Morales-Arraez, Diego Piombino, Guadalupe Garcia-Tsao, Florencia Pollarsky, Juan G. Abraldes, Joseph C. Ahn, Jorge Arnold, María de Fátima Higuera de la Tijera, Edilmar Alvarado-Tapias, Ashwani K. Singal, Eduardo Fuentes-López, Shiv Kumar Sarin, Marcela de Sousa Coelho, Victor Vargas, Robert S. Brown, Winston Dunn, Bashar M. Attar, Joaquín Cabezas, Melisa Dirchwolf, Meritxell Ventura-Cots, Jose A Gonzalez, José Altamirano, Adrián Narvaez, P. Nagaraja Rao, Marco Arrese, Anand V. Kulkarni, and Fernando Cairo
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Alcoholic liver disease, Cirrhosis, Time Factors, Alcohol Drinking, Alcoholic hepatitis, alcoholic hepatitis, Severity of Illness Index, Hepatitis, corticosteroids, Maddrey discriminant function, Cohort Studies, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Internal medicine, medicine, Humans, Retrospective Studies, Hepatology, business.industry, alcohol, cirrhosis, Hazard ratio, Middle Aged, medicine.disease, alcohol-associated liver disease, MELD, 030104 developmental biology, Methylprednisolone, Prednisolone, 030211 gastroenterology & hepatology, Female, Steroids, business, medicine.drug, alcoholic liver disease, steroids
Abstract: Background & Aims: Corticosteroids are the only effective therapy for severe alcohol-associated hepatitis (AH), defined by a model for end-stage liver disease (MELD) score >20. However, there are patients who may be too sick to benefit from therapy. Herein, we aimed to identify the range of MELD scores within which steroids are effective for AH. Methods: We performed a retrospective, international multi-center cohort study across 4 continents, including 3,380 adults with a clinical and/or histological diagnosis of AH. The main outcome was mortality at 30 days. We used a discrete-time survival analysis model, and MELD cut-offs were established using the transform-the-endpoints method. Results: In our cohort, median age was 49 (40-56) years, 76.5% were male, and 79% had underlying cirrhosis. Median MELD at admission was 24 (19-29). Survival was 88% (87-89) at 30 days, 77% (76-78) at 90 days, and 72% (72-74) at 180 days. A total of 1,225 patients received corticosteroids. In an adjusted-survival-model, corticosteroid use decreased 30-day mortality by 41% (hazard ratio [HR] 0.59; 0.47-0.74; p 51. The type of corticosteroids used (prednisone, pred-nisolone, or methylprednisolone) was not associated with sur-vival benefit (p = 0.247). Conclusion: Corticosteroids improve 30-day survival only among patients with severe AH, especially with MELD scores between 25 and 39. Lay summary: Alcohol-associated hepatitis is a condition where the liver is severely inflamed as a result of excess alcohol use. It is associated with high mortality and it is not clear whether the most commonly used treatments (corticosteroids) are effective, particularly in patients with very severe liver disease. In this worldwide study, the use of corticosteroids was associated with increased 30-day, but not 90-or 180-day, survival. The maximal benefit was observed in patients with an MELD score (a marker of severity of liver disease; higher scores signify worse disease) between 25-39. However, this benefit was lost in patients with the most severe liver disease (MELD score higher than 51). (C) 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Published: 2021

30. Real life experience of mycophenolate mofetil monotherapy in liver transplant patients

Author: Gilles Lebuffe, Odile Goria, F.R. Pruvot, Franck Saint-Marcoux, Jérôme Dumortier, Pierre Marquet, Guillaume Millet, Sébastien Dharancy, Juliette Boulanger, Valérie Canva, Emmanuel Boleslawski, Guillaume Lassailly, Alexandre Louvet, Philippe Mathurin, Olivier Boillot, Massih Ningarhari, Stéphanie Truant, Medhi El Amrani, Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), CHU Limoges, Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - UAR 3290 (MSAP), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Hôpital Claude Huriez [Lille], CHU Lille, Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and Service de Pharmacologie, toxicologie et pharmacovigilance [CHU Limoges]
Subjects: Graft Rejection, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Calcineurin Inhibitors, Urology, Renal function, Liver transplantation, Mycophenolate, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Hepatology, medicine.diagnostic_test, business.industry, Gastroenterology, Bayes Theorem, Mycophenolic Acid, medicine.disease, Liver Transplantation, Calcineurin, Transplantation, Regimen, Therapeutic drug monitoring, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Metabolic syndrome, business, Immunosuppressive Agents
Abstract: Summary Background Mycophenolate mofetil (MMF) monotherapy following liver transplantation (LT) remains controversial due to a risk of acute rejection. The aim of this study was to report the largest multicenter experience of the use a MMF monotherapy guided by therapeutic drug monitoring using pharmacoslope modeling and Bayesian estimations of the MPA inter-dose AUC (BEAUCMPA) before withdrawing calcineurin inhibitors (CNI) and to evaluate the benefit of MMF monotherapy. Methods MMF daily doses were adjusted to reach the BEAUCMPA target of 45 μg.h/mL. Then CNI were withdrawn and patients were followed on liver test and clinical outcomes. Main findings From 2000-2014, in 2 transplantation centers, 94 liver transplant recipients received MMF monotherapy 6.5 ± 4 years after LT. The mean BEAUCMPA was 45.5 ± 16 μg.h/mL. During follow-up, 4 patients experienced acute rejection (4%). During the first year, estimated glomerular filtration rate (eGFR) improved from 46.2 ± 10.5 to 49.1 ± 11.5 mL/kg/min (P = 0.025). Benefit persisted at year 5. In patients with metabolic syndrome, eGFR did not improve. Conclusion MMF monotherapy regimen appears usually safe and beneficial, with low risk of acute rejection and eGFR improvement. Therapeutic drug monitoring strategy seemed useful by identifying 14% of patients with low MMF exposure.
Published: 2021
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31. Sustained Remission After Treatment Withdrawal in Autoimmune Hepatitis: A Multicenter Retrospective Study

Author: Gérard Thiéfin, Pascal Renard, Anne Minello, Yasmina Ben Merabet, François Habersetzer, Solange Bresson-Hadni, Delphine Weil-Verhoeven, Thierry Thevenot, Brigitte Bernard-Chabert, Hélène Clot, Vincent Di Martino, Alexandra Heurgué-Berlot, Hervé Louvet, Didier Samuel, Coralie Barbe, Centre Hospitalier Universitaire de Reims (CHU Reims), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Paul Brousse, and Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Physiology, Biopsy, Azathioprine, Autoimmune hepatitis, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Gastroenterology, Hepatitis, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, Recurrence, Internal medicine, medicine, Humans, Child, Aged, Retrospective Studies, medicine.diagnostic_test, business.industry, Remission Induction, Adrenal cortex hormones, Retrospective cohort study, Gamma globulin, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Middle Aged, Hepatology, medicine.disease, 3. Good health, Hepatitis, Autoimmune, Withholding Treatment, Liver, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, business, Immunosuppressive Agents, Follow-Up Studies, medicine.drug, Autoimmune
Abstract: BACKGROUND: In patients with autoimmune hepatitis (AIH), relapse rates between 25 and 100% after treatment withdrawal have been reported. The optimal strategy for immunosuppressive treatment withdrawal is controversial. AIM: To identify the predictive factors of histological remission and to assess the relapse rate after treatment withdrawal in AIH patients with prolonged biochemical response. METHODS: Patients with AIH and sustained biochemical remission on first-line treatment were retrospectively included. Histological response was defined as complete regression of interface hepatitis and lobular necrosis and no or minimal portal inflammation and relapse as any elevation of serum aminotransferase or gammaglobulin/IgG levels. RESULTS: Sixty-two patients were included. Forty-seven had a biopsy after a median biochemical response of 49.7 months. Twenty-five of them were histological responders. Independent predictors of histological remission were older age (OR = 1.1; CI 95%: 1.0; 1.2), mild-to-moderate fibrosis at diagnosis (OR = 8; CI: 1.4; 47.6) and aspartate aminotransferases
Published: 2021
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32. PRODIGE 59-DURIGAST trial: A randomised phase II study evaluating FOLFIRI + Durvalumab ± Tremelimumab in second-line of patients with advanced gastric cancer

Author: Sabrina Pierre, Côme Lepage, Thierry Lecomte, Frédéric Bibeau, Karine Le Malicot, Aziz Zaanan, Stefano Kim, Astrid Lièvre, Thomas Aparicio, David Tougeron, Olivier Bouché, Harry Sokol, Pierre Laurent-Puig, Daniel Gonzalez, Farid El Hajbi, Frédéric Di Fiore, Christophe Louvet, Jérôme Desramé, Rosine Guimbaud, Camille Evrard, Benoist Chibaudel, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Mutualiste de Montsouris (IMM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Reims (CHU Reims), Régulation de la transcription et maladies génétiques (RTMG), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Chemistry, Oncogenesis, Stress and Signaling (COSS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Pontchaillou [Rennes], Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biochimie médicale [CHRU Besançon, hôpital Minjoz], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), 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), 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), Institut hospitalier Franco-Britannique [Levallois-Perret], Hôpital privé Jean Mermoz, AstraZeneca France, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lille-UNICANCER, Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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), Jonchère, Laurent, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse]
Subjects: Oncology, Male, medicine.medical_specialty, Durvalumab, Esophageal Neoplasms, Leucovorin, Phases of clinical research, [SDV.CAN]Life Sciences [q-bio]/Cancer, Adenocarcinoma, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, Immune checkpoint inhibitors, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Stomach Neoplasms, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Chemotherapy, Taxane, Hepatology, business.industry, Gastroenterology, Antibodies, Monoclonal, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Chemotherapy regimen, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Irinotecan, Treatment Outcome, Docetaxel, 030220 oncology & carcinogenesis, FOLFIRI, 030211 gastroenterology & hepatology, Camptothecin, Female, Esophagogastric Junction, Fluorouracil, France, business, Gastric cancer, Tremelimumab, medicine.drug
Abstract: International audience; Gastric or gastro-oesophageal junction (GEJ) adenocarcinomas present poor overall survival (OS). First-line chemotherapy regimen for patients with HER2-negative tumours is based on a doublet or triplet of fluoropyrimidine plus platinum salt ± taxane. Second-line chemotherapy (Docetaxel or Irinotecan) improves OS which nonetheless remains poor (around 5 months). The first results of immune checkpoint inhibitors (anti-PD-1) combined with chemotherapy in metastatic gastric and GEJ cancers were discordant in recent phase III trials. Data on dual-blockade (anti-PD-L1 or anti-PD-1 plus anti-CTLA-4) plus chemotherapy are lacking. DURIGAST is a randomised, multicenter, non-comparative, phase II study, evaluating safety and efficacy of FOLFIRI plus Durvalumab (anti-PD-L1) versus FOLFIRI plus Durvalumab and Tremelimumab (anti-CTLA-4) as second-line treatment of advanced gastric and GEJ adenocarcinoma. The primary objective is the rate of patients alive and without progression at 4 months. The main inclusion criteria are: patients with advanced gastric or GEJ adenocarcinoma, pre-treated with fluoropyrimidine + platinum salt ± taxane. Due to a lack of data on FOLFIRI, Durvalumab and Tremelimumab combination, a 2-step safety run-in phase has been performed before the randomised phase II. The safety run-in phase did not show any safety issue and the randomised phase II starts in September 2020.
Published: 2021
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33. Cannabis Use Is Inversely Associated with Overweight and Obesity in Hepatitis B Virus-Infected Patients (ANRS CO22 Hepather Cohort)

Author: Barré, Tangui, Pol, Stanislas, Ramier, Clémence, Di Beo, Vincent, Carrat, Fabrice, Bureau, Morgane, Bourlière, Marc, Dorival, Céline, Serfaty, Lawrence, Asselah, Tarik, Boursier, Jérôme, Marcellin, Fabienne, Carrieri, Patrizia, Fontaine, Hélène, Protopopescu, Camelia, Alric, Laurent, Bonnet, Delphine, Payssan-Sicart, Virginie, Pomes, Chloe, Zoulim, Fabien, Maynard, Marianne, Bai, Roxane, Hucault, Lucie, Bailly, François, Raffi, François, Billaud, Eric, Boutoille, David, Lefebvre, Maeva, André-Garnier, Elisabeth, Cales, Paul, Hubert, Isabelle, Lannes, Adrien, Lunel, Françoise, Boyer, Nathalie, Giuily, Nathalie, Castelnau, Corinne, Scoazec, Giovanna, Rousseaud, Emilie, Vallet-Pichard, Anaïs, Sogni, Philippe, Ledinghen, Victor De, Foucher, Juliette, Hiriart, Jean-Baptiste, M'Bouyou, Jancell, Irlès-Depé, Marie, Si Ahmed, Si Nafa, Oules, Valérie, Tran, Albert, Anty, Rodolphe, Gelsi, Eve, Truchi, Régine, Thabut, Dominique, Hammeche, Saloua, Moussali, Joseph, Causse, Xavier, Dieuleveult, Barbara De, Ouarani, Brahim, Labarrière, Damien, Ganne, Nathalie, Grando-Lemaire, Véronique, Nahon, Pierre, Brulé, Séverine, Ulker, Betul, Guyader, Dominique, Jezequel, Caroline, Brener, Audrey, Laligant, Anne, Rabot, Aline, Renard, Isabelle, Habersetzer, François, Baumert, Thomas, Doffoel, Michel, Mutter, Catherine, Simo-Noumbissie, Pauline, Razi, Esma, Bronowicki, Jean-Pierre, Barraud, Hélène, Bensenane, Mouni, Nani, Abdelbasset, Hassani-Nani, Sarah, Bernard, Marie-Albertine, Pageaux, Georges-Philippe, Larrey, Dominique, Meszaros, Magda, Metivier, Sophie, Bureau, Christophe, Morales, Thibault, Peron, Jean Marie, Robic, Marie Angèle, Decaens, Thomas, Faure, Marine, Froissart, Bruno, Hilleret, Marie-Noelle, Zarski, Jean-Pierre, Riachi, Ghassan, Goria, Odile, Paris, Fatima, Montialoux, Hélène, Leroy, Vincent, Amaddeo, Giuliana, Varaut, Anne, Simoes, Mélanie, Amzal, Rachida, Chazouillières, Olivier, Andreani, Tony, Angoulevant, Bénédicte, Chevance, Azeline, Samuel, Didier, Antonini, Teresa, Coilly, Audrey, Duclos Vallée, Jean-Charles, Tateo, Mariagrazia, Abergel, Armand, Reymond, Maud, Brigitte, Chanteranne, Benjamin, Buchard, Muti, Léon, Geist, Claire, Conroy, Guillaume, Riffault, Raphaëlle, Rosa, Isabelle, Barrault, Camille, Costes, Laurent, Hagège, Hervé, Loustaud-Ratti, Véronique, Carrier, Paul, Debette-Gratien, Maryline, Mathurin, Philippe, Lassailly, Guillaume, Lemaitre, Elise, Canva, Valérie, Dharancy, Sébastien, Louvet, Alexandre, Minello, Anne, Latournerie, Marianne, Bardou, Marc, Mouillot, Thomas, d'Alteroche, Louis, Barbereau, Didier, Nicolas, Charlotte, Elkrief, Laure, Jaillais, Anaïs, Gournay, Jérôme, Chevalier, Caroline, Archambeaud, Isabelle, Habes, Sarah, Portal, Isabelle, Gelu-Simeon, Moana, Saillard, Eric, Lafrance, Marie-Josée, Catherine, Lucie, Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), ESIM - Déterminants Sociaux de la Santé et du Recours aux Soins (DS3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépato-gastro-entérologie, Assistance Publique - Hôpitaux de Marseille (APHM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital de Hautepierre [Strasbourg], Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), and BOURGEAIS, Véronique
Subjects: Hepatitis B virus, medicine.medical_specialty, Cirrhosis, [SDV]Life Sciences [q-bio], Aucun, Overweight, medicine.disease_cause, Virus, 03 medical and health sciences, Hepatitis B, Chronic, 0302 clinical medicine, Internal medicine, medicine, Humans, Pharmacology (medical), Obesity, ComputingMilieux_MISCELLANEOUS, Cannabis, 030304 developmental biology, Pharmacology, 0303 health sciences, biology, Cannabinoids, business.industry, Liver Neoplasms, Hepatitis B, biology.organism_classification, medicine.disease, digestive system diseases, 3. Good health, [SDV] Life Sciences [q-bio], Complementary and alternative medicine, Hepatocellular carcinoma, Cohort, cannabis, obesity, overweight, socioeconomic status, 030211 gastroenterology & hepatology, medicine.symptom, business
Abstract: International audience; Background: Chronic hepatitis B virus (HBV) infection may evolve into cirrhosis and hepatocellular carcinoma, and this progression may be accelerated by specific risk factors, including overweight and obesity. Although evidence for a protective effect of cannabis use on elevated body weight has been found for other populations, no data are available for HBV-infected patients.Aims: We aimed to identify risk factors (including cannabis use) for overweight and obesity in patients with HBV chronic infection.Methods: Using baseline data from the French ANRS CO22 Hepather cohort, we performed two separate analyses, one using “central obesity” (based on waist circumference) and the other “overweight” and “obesity” (based on body mass index) as outcomes. Logistic and multinomial regressions were used to model central obesity and overweight/obesity, respectively.Results: Among the 3706 patients in the study population, 50.8% had central obesity, 34.7% overweight, and 14.4% obesity. After multivariable adjustment, current cannabis use was associated with a 59% lower risk of central obesity compared with no lifetime use (adjusted odds ratio [95% CI]: 0.41 [0.24 to 0.70]). It was also associated with a 54% and 84% lower risk of overweight (adjusted relative risk ratio [95% CI]: 0.46 [0.27 to 0.76]) and obesity (0.16 [0.04 to 0.67]), respectively.Conclusions: Cannabis use was associated with lower risks of overweight and obesity in patients with HBV chronic infection. Future studies should test whether these potential benefits of cannabis and cannabinoid use translate into reduced liver disease progression in this high-risk population.
Published: 2021
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34. Monitoring levels of circulating cell‐free DNA in patients with metastatic colorectal cancer as a potential biomarker of responses to regorafenib treatment

Author: Dewi Vernerey, Thierry André, Isabelle Trouilloud, Brice Pastor, Thibault Mazard, A.R. Thierry, Cynthia Sanchez, Audrey Bauer, Benoit Roch, Christophe Louvet, Marine Jary, Simon Azan, Christophe Tournigand, Antoine Adenis, Julie Henriques, Gestionnaire, Hal Sorbonne Université, Institut du Cancer de Montpellier (ICM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service d'Oncologie Médicale [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), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Cooperator Multidisciplinary Oncology Group (GERCOR), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Henri Mondor, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut mutualiste Monsouris (IMM), Service d'Oncologie Médicale [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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])
Subjects: 0301 basic medicine, Oncology, Neuroblastoma RAS viral oncogene homolog, Male, Cancer Research, Colorectal cancer, Pyridines, [SDV]Life Sciences [q-bio], Mutant, medicine.disease_cause, chemistry.chemical_compound, 0302 clinical medicine, Medicine, Neoplasm Metastasis, cfDNA, Research Articles, RC254-282, Regorafenib, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, General Medicine, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Predictive biomarker, 030220 oncology & carcinogenesis, Molecular Medicine, Female, KRAS, Colorectal Neoplasms, Cell-Free Nucleic Acids, Research Article, medicine.medical_specialty, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Genetics, Biomarkers, Tumor, Humans, In patient, Mutant ctDNA, Aged, business.industry, Phenylurea Compounds, Liquid Biopsy, circulating DNA, medicine.disease, Survival Analysis, Circulating Cell-Free DNA, 030104 developmental biology, chemistry, Potential biomarkers, Tumor response, business
Abstract: Circulating cell‐free DNA (cfDNA) contains circulating tumor DNA (ctDNA), which can be obtained from serial liquid biopsies to enable tumor genome analysis throughout the course of treatment. We investigated cfDNA and mutant ctDNA as potential biomarkers to predict the best outcomes of regorafenib‐treated metastatic colorectal cancer (mCRC) patients. We analyzed longitudinally collected plasma cfDNA of 43 mCRC patients prospectively enrolled in the phase II TEXCAN trial by IntPlex qPCR. Qualitative (KRAS, NRAS, BRAFV600E mutations) and quantitative (total cfDNA concentration, mutant ctDNA concentration, mutant ctDNA fraction) parameters were correlated with overall survival (OS) and progression‐free survival (PFS). When examined as classes or continuous variables, the concentrations of total cfDNA, mutant ctDNA, and, partly, mutant ctDNA fraction prior to regorafenib treatment correlated with OS. Patients with baseline cfDNA > 26 ng·mL−1 had shorter OS than those with cfDNA value below this threshold (4.0 vs 6.9 months; log‐rank P = 0.0366). Patients with baseline mutant ctDNA > 2 ng·mL−1 had shorter OS than those with mutant ctDNA below this threshold (log‐rank P = 0.0154). We show that pretreatment cfDNA and mutant ctDNA levels may identify mCRC patients that may benefit from regorafenib treatment., Circulating cell‐free DNA (cfdNA) was extracted from longitudinal blood collection of 43 mCRC patients treated by regorafenib. Qualitative (RAS, BRAFV600E mutations) and quantitative (cfDNA concentration, mutant circulating tumor DNA (ctDNA) concentration, mutant ctDNA fraction) parameters were correlated with survival. We show that pretreatment cfDNA and mutant ctDNA levels may identify mCRC patients that may benefit from regorafenib treatment.
Published: 2021
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35. Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

Author: Cécile Couchoud, Florian Bayer, Carole Ayav, Clémence Béchade, Philippe Brunet, François Chantrel, Luc Frimat, Roula Galland, Maryvonne Hourmant, Emmanuelle Laurain, Thierry Lobbedez, Lucile Mercadal, Olivier Moranne, Abdelhamid Abbassi, Alain Debure, Abdallah Guerraoui, Abdelatif Benmoussa, Abdelaziz Hamani, Abdelaziz Ziane, Abdelhamid Nefti, Abdelkader Hadj, Abderrahim El Amari, Abderrahmane Ghazali, Abo Bakr Abd El Fatah Mohamed, Achour Laradi, Adel Ben Ahmed, Adel Sahar, Adele Pillet, Adeline Lacraz, Adnan Moinat, Afshin Massoumi, Agathe Pardon, Agnes Caillette Beaudoin, Agnes Chapelet Debout, Agnes Mariot, Ahmed Rachi, Aida Afiani, Aime Remy Boula, Al Jalaby, Alain Cremault, Alain Fournier, Alain Jeanson, Alain Lyon, Alain Nony, Alain Robert, Alain Slingeneyer, Alanor Agnes Labatide, Albane Brodin Sartorius, Albert Bensman, Albert Fournier, Alex Ranlin, Alex Vido Sandor, Alexandra Colombo, Alexandra Duhem, Alexandra Stancu, Alexandre Dufay, Alexandre Dumoulin, Alexandre Ebel, Alexandre Klein, Alexandre Martin, Alexandre Mouneimne, Alexandre Seidowsky, Alfio De Martin, Alfredo Zannier, Ali Aizel, Ali Hafi, Ali Zineddine Diddaoui, Alim Heyani, Alina Mocanu, Alina Preda, Aline Hafi, Aline Talaszka, Alyette Duquesne, Amar Amaouche, Amel Ghemmour, Amelie Simon, Amina Skalli, Amine Boukadida, Amr Ekhlas Ragab Eid, Ana Fedorca, Anabelle Baillet, Anais Poyet, Ancuta Bouffandeau Giorgita, Anderson Ratsimbazafy, Andre Pruna, Angel Argiles, Angelo Testa, Ann Karolien Vandooren, Anne Jolivot, Anne Kolko Labadens, Anne Lataste, Anne Maisin, Anne Paris, Anne Sechet, Anne Wuillai, Anne Elisabeth Heng, Anne Gaelle Josse, Anne Helene Querard, Anne Helene Reboux, Anne Laure Adra, Anne Laure Faller, Anne Laure Leclerc, Anne Laure Poitou, Annie Lahoche Manucci, Antoine Jacquet, Antoine Pommereau, Antoine Thierry, Arezki Adem, Arielle Chapelet, Arnaud Del Bello, Arnaud Delezire, Arnaud Garnier, Arnaud Guerard, Arnaud Klisnick, Arnaud Lionet, Arnaud Roccabianca, Arnaud Stolz, Arthur Capdeville, Asma Allal, Assem Alrifai, Assetou Diarrassouba, Assia Djema, Assia Ferhat Carre, Astrid Godron Dubrasquet, Atman Haddj Elmrabet, Audrey Jegado, Aurelia Bertholet Thomas, Aurelie Davourie Salandre, Aurelie Pajot, Aurelien Lorthioir, Aurelien Tiple, Aurore Sury, Ayman Abokasem, Ayman Sarraj, Bachir Henaoui, Baher Chaghouri, Bassem Wehbe, Beatrice Ball, Beatrice Viron, Belkassem Issad, Benedicte Hodemon Corne, Benedicte Janbon, Benjamin Deroure, Benjamin Savenkoff, Benoit Jonon, Benoit Vendrely, Benyakoub Djelaleddine, Bernard Ohry, Bernard Painchart, Bernard Strullu, Bernard Temperville, Bertin Ebikili, Bertrand Hacq, Bertrand Morel, Bilal Aoun, Blanca Muniz, Bouchra Chlih, Brahim Amara, Brice Mayor, Brigitte Gilson, Brigitte Llanas, Brigitte Zins, Bruno Bourgeon, Bruno Coevoet, Bruno Guery, Bruno Legallicier, Bruno Paris, Bruno Ranchin, Bruno Seigneuric, Camelia Ghiciuc Dita, Camelia Prelipcean, Carine Achard Hottelart, Carine Diet, Carlos Frangie, Carlos Vela, Carmina Muresan, Carole Deprele, Caroline Araujo, Caroline Bidault, Caroline Creput, Caroline Delclaux, Caroline Du Halgouet, Caroline Favennec, Caroline Freguin, Caroline Gourraud Vercel, Caroline Mesguen, Caroline Ndomo Obama, Caroline Poitou, Caroline Preissig Dirhold, Caroline Roubiou, Catherine Albert, Catherine Bessin, Catherine De Marion Gaja, Catherine Godart, Catherine Lasseur, Catherine Leocardi, Catherine Lumbroso, Catherine Melander, Catherine Michel, Catherine Quere Maurouard, Catherine Rouannet, Catherine Taddei, Cathy Verove, Cecile Guiraud, Cecile Tafelin, Cecile Turc Baron, Cedric Formet, Cedric Pinier, Celia Lessore De Ste Foy, Celine Granolleras, Chaouki Bennini, Charles Cartou, Charles Chazot, Charlotte Jouzel, Cherif Badid, Christa Roubicek, Christel Viaud, Christelle Verrier, Christian Chuet, Christian Combe, Christian Dabot, Christian Duvic, Christian Emond, Christian Lagarde, Christian Lamotte, Christian Pain, Christiane Mousson, Christie Lorriaux, Christine Beauchamp, Christine Fumeron, Christine Le Gurun, Christine Leroy, Christine Pietrement, Christine Richer, Christophe Bouaka, Christophe Charasse, Christophe Goupy, Christophe Ridel, Cindy Castrale, Cindy Detourne, Clair Francois, Claire Presne, Claire Trivin, Clarissa Von Kotze, Claude Bernard, Claude Bonniol, Claude Desvergnes, Claude Raharivelina, Claudia Nistor, Claudine Gueret, Claudine Lloret, Claudine Saltiel, Clelia Rosati, Clementine Rabate, Corina Stanescu, Corinne Ferrandini, Corinne Guibergia, Corinne Lemoine, Corinne Passeron, Cynthia Kahil, Cyril Garrouste, Cyril Vo Van, Cyrille Jolimoy, Dalila Kesraoui, Damien Jolly, Damien Thibaudin, Dan Teboulle, Daniel Daubresse, Daniel Louvet, Daniel Rasamimanantsoa, Daniel Toledano, Daniela Babici, Daniela David, Daniela Dincu, Danielle Bruno, Delia May, Delphine Haussaire, Delphine Henriet Viprey, Denis Bugnon, Denis Fouque, Denis Morin, Derradji Nour, Diab Mohamed Mahmoud, Diana Istrati Cristescu, Didier Aguilera, Didier Coste, Didier Hamel, Didier Le Chapois, Didier Testou, Dilaver Erbilgin, Djamal Dahmane, Doan Bui Quang, Dominique Bertrand, Dominique Besnier, Dominique Blanchier, Dominique Briffa, Dominique Caux, Dominique Durand, Dominique Fleury, Dominique Guerrot, Dominique Hestin, Dominique Jaubert, Dominique Joly, Dominique Lombart, Dominique Pagniez, Dominique Pierre, Dominique Schohn, Donatien Ikonga, Dorina Visanica, Dorothee Bazin, Edouard Boury, Edouard Maksour, Ekoue Agbonon, Elarbi Harrami, Elena Marcu, Elena Tudorache, Elisabeth Caniot, Elisabeth Semjen, Elisabeth Tomkiewicz, Elise Scheidt, Elke Gaboriau, Elodie Lamouroux, Elsa Guiard, Elsa Martin Passos, Emerson Nsembani, Emilie Fache, Emilie Kalbacher, Emilie Pambrun, Emilie Pincon, Emma Allain Launay, Emmanuel Baron, Emmanuel Dupuis, Emmanuel Villar, Emmanuelle Charlin, Emmanuelle Hecquet, Emmanuelle Kohler, Emmanuelle Rosier, Enrique Figueroa, Eric Azoulay, Eric Canivet, Eric Daugas, Eric Gauthier, Eric Laruelle, Eric Le Guen, Eric Legrand, Eric Moumas, Eric Postec, Eric Prinz, Eric Renaudineau, Estelle Desport, Estelle Ricard Sutra, Etienne Berard, Etienne Ged, Etienne Robin, Eve Vilaine, Evelyne Bargas, Evelyne Mac Namara, François Combarnous, Fatima Yazbeck, Fabien Gerard, Fabien Metivier, Fabien Parazols, Fabien Soulis, Fabrice Garnier, Fadhila Pech Messaoudene, Fadi Haidar, Fanny Boullenger, Fanny Lepeytre, Fanny Leroy, Fares Frejate, Farid Bellahsene, Farid Bellhasene, Farid Saidani, Fatouma Toure, Faycal Kriaa, Fazia Nemmar, Fernando Vetromile, Florence Chalmin, Florence Lucats, Florence Sens, Florence Villemain, Florent Plasse, Fouad Lebhour, Francis Schillinger, Franck Berge, Franck Bourdon, Franck Bridoux, Franck Reynaud, Francois Babinet, Francois Basse, Francois Chantrel, Francois Clair, Francois Coulomb, Francois De Cornelissen, Francois Glowacki, Francois Marchal, Francois Maurice, Francois Nobili, Francois Pourreau, Francois Provot, Francois Roux Amani, Francoise Broux, Francoise Bulte, Francoise Heibel, Francoise Leonetti, Francoise Moussion Schott, Frank Le Roy, Frederic Besson, Frederic Lavainne, Frederic Tollis, Frederique Bocquentin, Frederique Meeus, Frederique Vecina, Friederike Von Ey, Gabriel Balit, Gabriel Choukroun, Gabriel Gruget, Gabriel Huchard, Gabriella Golea, Gabrielle Duneau, Gaelle Lefrancois, Gaelle Pelle, Gaetan Lebrun, Genevieve Dumont, Georges Brillet, Georges Deschenes, Georges Mourad, Georges Stamatakis, Geraldine Cazajous, Geraldine D'ythurbide, Geraldine Robitaille Wiart, Gerard Cardon, Gerard Champion, Gerard Deschodt, Gerard Mangenot, Gerard Motte, Gerard Schortgen, Ghada Boulahia, Ghassan Maakaroun, Ghylene Bourdat Michel, Gilbert Zanetta, Gilles Hufnagel, Gilles Messier, Giorgina Piccoli, Gregoire Couvrat Desvergnes, Guillaume Bobrie, Guillaume Bonnard, Guillaume Clement, Guillaume Jean, Guillaume Queffeulou, Guillaume Seret, Guillaume Vernin, Guy Delavaud, Guy Lambrey, Guy Rostoker, Gwenaelle Poussard, Gwenaelle Roussey Kesler, H. Leon, Habib Aboubekr, Hacene Boulechfar, Hacene Sekhri, Hadia Hebibi, Hadjira Benalia, Hafed Fessi, Hafsabhai Atchia, Haiat Bittar, Hakim Maiza, Hakim Mazouz, Hamid El Ali, Hammouche Bougrida, Hans Van Der Pijl, Hassan Lokmane, Hassane Izzedine, Hassen Adda, Helene De Preneuf, Helene Leray, Helene Philippot, Henri Boulanger, Henri Merault, Henri Renaud, Herve Bonarek, Herve Maheut, Hilaire Nzeyimana, Hocine Mehama, Hocine Zaidi, Hugo Weclawiak, Hugues Flodrops, Huseyin Karaaslan, Ibrahim Haskour, Ihssen Belhadj, Imad Almoubarak, Imad Haddad, Ines Castellano, Ines Ferrandiz, Ioana Daniliuc, Ioana Darie, Ioana Enache, Ionut Prunescu, Irenee Djiconkpode, Irina Shahapuni, Isabelle Bouchoule, Isabelle Devriendt, Isabelle Kazes, Isabelle Kolb, Isabelle Landru, Isabelle Poli, Isabelle Rey, Isabelle Segalen, Isabelle Selcer, Isabelle Vernier, Isabelle Vrillon, Ismahane Guenifi, J. Dominique Gheerbrandt, Jacky Potier, Jacques Becart, Jacques Cledes, Jacques Ducros, Jacques Duvic, Jacques Fourcade, Jacques Gaultier, Jacques Jurine, Jacques Lebleu, Jacques Ollier, Jacques Ibsen Charles, Jamal Yazji, Janette Mansour, Jean Arnautou, Jean Brocard, Jean Carolfi, Jean Montoriol, Jean Baptiste Gouin, Jean Bernard Palcoux, Jean Christophe Bendini, Jean Claude Aldigier, Jean Claude Alphonse, Jean Daniel Delbet, Jean Francois Bonne, Jean Francois Cantin, Jean Francois De Fremont, Jean Francois Dessassis, Jean Francois Subra, Jean Francois Valentin, Jean Francois Verdier, Jean Jacques Dion, Jean Jacques Haultier, Jean Jacques Montseny, Jean Louis Bacri, Jean Louis Bouchet, Jean Luc Mahe, Jean Marc Chalopin, Jean Marc Gabriel, Jean Marc Hurot, Jean Marc Lanau, Jean Marie Batho, Jean Marie Coulibaly, Jean Michel Hardin, Jean Michel Marc, Jean Michel Poux, Jean Michel Rebibou, Jean Michel Tivollier, Jean Noel Ottavioli, Jean Paul Faucon, Jean Paul Imiela, Jean Paul Jaulin, Jean Paul Masselot, Jean Paul Ortiz, Jean Philippe Bourdenx, Jean Philippe Devaux, Jean Philippe Hammelin, Jean Pierre Rivory, Jean Pierre Wauquier, Jean Rene Larue, Jean Rene Mondain, Jean Sebastien Borde, Jean Simon Virot, Jean Yves Bosc, Jedjiga Achiche, Jennifer Parasote, Jeremie Diolez, Jerome Harambat, Jerome Potier, Jerome Sampol, Jihad Mustel, Jean Jacques Lefevre, Jocelyne Maurizi, Joel Gamberoni, Joelle Claudeon, Joelle Terzic, Joffrey Rogol, Johnny Sayegh, Jorge Cardozo, Jose Brasseur, Jose Guiserix, Joseph Barsumau, Julie Albaret, Julie Beaume, Julie Sohier Attias, Julien Dehay, Julien Hogan, Julien Journet, Julien Ott, Juliette Baleynaud, Justine Bacchetta, Justine Faucher, Kamel Yousfi, Karim Dardim, Karine Clabault, Karine Moreau, Kedna Thomas, Khaled Sirajedine, Khalil Chedid, Khalil El Kaeoui, Khalil El Karoui, Khedidja Bouachi, Kheira Hue, Khuzama El Nasser, Kodso Akposso, Kristian Kunz, Krzysztof Bijak, Lilia Kihal, L. Rasoloarijaona, Laid Harbouche, Larbi Bencheikh, Larbie Lamriben, Latifa Hanafi, Laura Braun Parvez, Laure Champion, Laure Croze, Laure Eprinchard, Laure Patrier, Laurence Nicolet, Laurence Vrigneaud, Laurent Duflot, Leandre Mackaya, Leila Chenine, Leon Odry, Lili Taghipour Tamiji, Lilia Antri Bouzar, Liliane Ngango Nga Messi, Lionel Le Mouellic, Lise Mandart, Lise Weis, Lise Marie Pouteau, Lora Georgieva, Lorita Vitanova, Lotfi Chalabi, Luc Delvallez, Luc Fromentin, Luc Marty, Luc Monjot, Luciana Spataru, Lucie Bessenay, Lucie Boissinot, Lucie Wajsbrot, Lucien Rakoff, Ludivine Lebourg, Lydie Perez, Lyliane Lafage, Lynda Azzouz, Madeleine Dumoulin, Messaoud Ouziala, Maan Joseph, Mabrouk Brahimi, Maeva Wong Fat, Magalie Fort, Magued Nakhla, Mahdi Abtahi, Mahen Albadawy, Mahmoud Alouach, Mahmoud Mezghani, Maite Daroux, Maklouf Boukelmoune, Malek Dhib, Malik Touam, Malina Dubau, Mamadou Balde, Man Nguyen Khoa, Manfred Ismer, Manolie Mehdi, Manon Laforet, Marc Bouiller, Marc Eugene, Marc Fila, Marc Hazzan, Marc Kribs, Marc Ladriere, Marc Lebot, Marc Padilla, Marc Souid, Marcel Marraoui, Maren Burbach, Maria Manescu, Maria Eugenia Noguera Gonzalez, Mariana Revenco, Marianne Terrasse, Marie Essi, Marie Alice Macher, Marie Beatrice Nogier, Marie Cecile Cazin, Marie Christine Schweitzer Camoin, Marie Christine Thouret, Marie Claude Hannaert, Marie France Servel, Marie Helene Chabannier, Marie Jeanne Coudert Krier, Marie Noelle Catoliquot, Marie Paule Guillodo, Marie Sophie Gavard, Marie Xaviere Vairon Codaccioni, Marina Rabec, Marine Freist, Marion Gauthier, Marion Lemaire, Marion Mehrenberger, Marion Venot, Marios Pongas, Marlene Beaubrun Diant, Martial Levannier, Martine Bertaux, Mathieu Jablonski, Mathieu Sacquepee, Mathilde Dargelos, Mathilde Lemoine, Mathilde Tamain, Matthieu Monge, Matthieu Reberolle, Maud Cousin, Maud Francois, Maurice Baron, Maxime Hoffmann, Maxime Ingwiller, Maxime Touzot, Mederick Mohajer, Mehadji Maaz, Melanie Hanoy, Melanie Marroc, Melodie Cuny, Menno Van Der Straaten, Mf. Serveaux, Michel Basteri, Michel Fen Chong, Michel Hecht, Michel Massad, Michel Normand, Michel Olmer, Michel Tolani, Michel Tsimaratos, Michele Hemery, Michele Kessler, Miguel Esposito, Milad Shenouda, Mimi Kareche, Mina Khalili, Mirella Diaconita, Mohamad Khair Rifard, Mohamed Aladib, Mohamed Belmouaz, Mohamed Brahim, Mohamed Diouani, Mohamed Fodil Cherif, Mohamed Jamali, Mohamed Maghlaoua, Mohamed Meddeb, Mohamed Ramdane, Mohamed Rifaat, Mohamed Sharifull Islam, Mohamed Adnan Abbade, Mokhtar Amrandi, Mokhtar Chawki, Monica Ciobotaru, Monica Indrieis, Monique Chanas, Monique Hoarau, Monzer Tomeh, Moufida Bellou, Mouloud Bouzernidj, Mounia Ammor, Mounir Guergour, Mountassir Benzakour, Mourad Hachicha, Moussa Coulibaly, Mustafa Smati, Mustapha Al Morabiti, Mustapha Amirou, Myriam Isnard, Myriam Pastural, Myriam Pujo, Nourredine Boumendjel, Nabil Majbri, Nabila Goumri, Nadege Mingat, Nader Bassilios, Nadia Kerkeni, Nadia Sedrati, Nadia Soltani, Nadine Maroun, Nadine Neyrat, Nahn Luang, Najeh El Esper, Naji Ammar, Nasredine Ghali, Nasser Hamdini, Natacha Noel, Natacha Potelune, Nathalie Maisonneuve, Nathalie Pertuiset, Nathalie Raynal, Nathalie Vittoz, Nazim Terki, Nelly Castin, Nestor Nankeu, Nicolas Bouvier, Nicolas Keller, Nicolas Legros, Nicolas Peters, Nicolas Quirin, Nicole Lefrancois, Nicole Monnier, Nicole Rance, Niels Bruckmann, Noel Mertens, Nolwenn Lorcy, Olivia Gilbert, Olivier Coldefy, Olivier Drouineau, Olivier Dunand, Olivier Fritz, Olivier Imhoff, Olivier Kourilsky, Olivier Lavelle, Olivier Papin, Olivier Roques, Ophelie Le Maner, Oussamah Fikri Benbrahim, Pablo Antonio Erina Torres, Pablo Antonio Urena Torres, Paolo Malvezzi, Pascal Bindi, Pascal Cluzel, Pascal Fontanier, Pascal Wheatley, Pascale Depraetre, Pascale Dubosq, Pascale Halin, Pascale Sebahoun, Pascale Siohan, Pascale Testevuide, Patrice Deteix, Patrice Nolen, Patricia Hue, Patricia Lemarchand, Patrick Donnadieu, Patrick Fievet, Patrick Fohrer, Patrick Francais, Patrick Giraud, Patrick Hallonet, Patrick Henri, Patrick Michaut, Patrick Niaudet, Patrick Pauly, Patrick Thomas, Patrik Deleaval, Paul Finielz, Paul Stroumza, Paule Hardy Yverneau, Pauline Caillard, Pedro Palacin, Perrine Aubertin, Philippe Attias, Philippe Chauveau, Philippe Coindre, Philippe Coste, Philippe Dubot, Philippe Fournier, Philippe Hiernaux, Philippe Jousset, Philippe Lan Yue Wah, Philippe Lang, Philippe Le Cacheux, Philippe Martin Dupont, Philippe Michel, Philippe Mirgaine, Philippe Moriniere, Philippe Nicoud, Philippe Rieu, Philippe Rousseau, Philippe Sporer, Philippe Thorel, Philippe Vanhille, Philippe Vigeral, Philippe Zaoui, Pierre Bataille, Pierre Brignon, Pierre Filipozzi, Pierre Housset, Pierre Peyronnet, Pierre Ramperez, Pierre Vautrin, Pierre Alexandre Michel, Pierre Francois Westeel, Pierre Louis Carron, Pierre Yves Durand, Pierrot Parent, Piotr Seniuta, François Kuentz, Rabah Fraoui, Rachel Tetaz, Rachid Amaria, Rachid Bourouma, Rachid Djeffal, Rachida Nebbad, Radia Allal, Radu Dimulescu, Rafaat Boustani, Rafik Mesbah, Raifat Makdassi, Raji Diab, Raluca Puslenghea, Raoul Roura, Rateb Khayat, Raymond Azar, Raymond Frayssinet, Regine Monkam, Rehouni Boulahrouz, Remi Boudet, Renato Demontis, Renaud Gansey, Rene Cuvelier, Renee Schmitt, Reschad Noordally, Reynald Binaut, Rezkallah Latif, Richard Dufresne, Richard Montagnac, Richard Reade, Robert Genin, Robert Novo, Rocsana Fickl, Roger Dufresne, Roger Magnol, Roland Issautier, Romain Mortelette, Ronan Delaval, Ronan Lohro, Roseline M'barga, S. Beau, Clémentine Dupuis, Marie Jacques Vidil, Sabria Hacini, Said Dahmoune, Saliha Lekhal, Salima Ahriz Sakso, Salima Saksi, Salvatore Citarda, Samir Boubenider, Samuel Kassis, Sandra Verhille, Sandrine Genestier, Sandrine Muller, Saoussen Krid, Sarah Richter, Sebastien Delbes, Sebastien Mailliez, Sebastien Veillon, Sébastien Nony, Seddick Benarbia, Severine Beaudreuil, Sidi Ali Benyaghla, Simon Duquennoy, Simona Baluta, Simona Boncila, Sonia Mzoughi, Sonia Ribal, Sophie Acamer, Sophie Chauvet, Sophie Girerd, Sophie Ozenne, Sophie Parahy, Sophie Rubens Duval, Sophie Taque, Soraya Menouer, Soumaya Chargui, Stanislas Bataille, Stephane Barbier, Stephane Billion, Stephane Roueff, Stephane Torner, Stephane Jean Martin, Stephanie Coupel, Sylvie Cloarec, Sylvie Lavaud, Sylvie Leou, T. Chatelet, Tania Onesta, Tassadit Benhabib, Tayeb Bensalem, Theodora Dimulescu, Theophile Sawadogo, Thibault Dolley Hitze, Thierry Baranger, Thierry Boudemaghe, Thierry Hannedouche, Thierry Krummel, Thierry Milcent, Thomas Dervaux, Thomas Guincestre, Thomas Kofman, Thomas Raphael, Thomas Sadreux, Tim Ulinski, Tiphaine Guyon Roger, Tomas Serrato, Tomek Kofman, Tony Wong, Toufik Boubia, Ubald Assogba Gbindoun, Usama Khuzaie, Valerie Caudwell, Valerie Chatelet, Valerie Crougneau, Valerie De Precigout, Valerie Drouillat, Valerie Galantine, Valerie Granveau Hugot, Valerie Leroy, Veronique Boubia, Veronique Falque, Veronique Fournier, Veronique Queron, Veronique Viviani, Victor Gueuttin, Victor Panescu, Victorio Menoyo Calonge, Viet Nguyen, Vincent Allot, Vincent Delattre, Vincent Leduc, Vincent Pradier, Violaine Emal Aglae, Viorica Badulescu, Virginia Molina, Virginie Besson, Virginie Chaigne, Waddah Jaber, Wael Boudi, Wael El Haggan, Wen Qin Guillon, Wided Tabbi Aneni, William Hanf, Wladimir Kohn, Xavier Bellenfant, Xavier Moreau Gaudry, Yahsou Delmas, Yannick Knefati, Yannick Saingra, Yannick Tirolien, Youssef Mann, Yvan Brunak, Yves Dimitrov, Yves Doussy, Yves Tanter, Zaid Benabid, Zaara Soltani, Zacharia Boukerroucha, Zafer Takla, Zana Ramanantsialonina, Zara Dickson, Zead Tubail, Zoe Koochaki Pour, Zohra Boukhalfa, Zohra Jacquot, Agence de la biomédecine [Saint-Denis la Plaine], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Caen Normandie (UNICAEN), Normandie Université (NU), CALYDIAL Vienne, Partenaires INRAE, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Armand Trousseau [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service d'Epidémiologie et Evaluations Cliniques [CHRU Nancy] (Pôle S2R), Centre Universitaire des Maladies Rénales [CHU Caen] (CUMR Caen), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Groupe hospitalier de la région de Mulhouse Sud-Alsace (GHRMSA), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Assistance Publique - Hôpitaux de Marseille (APHM), Service de diabétologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Service de Diabétologie [CHU Pitié-Salpétrière], 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: 0301 basic medicine, Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Hemodialysis, Home, Disease, MESH: COVID-19 / therapy, registry, Ambulatory Care Facilities, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, MESH: Aged, 80 and over, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, 80 and over, Prevalence, covid, dialysis, epidemiology, mortality, Aged, Aged, 80 and over, COVID-19, Case-Control Studies, Critical Care, Female, France, Humans, Incidence, Middle Aged, Patient Acuity, Protective Factors, Registries, Renal Dialysis, SARS-CoV-2, Sex Factors, Hypoalbuminemia, MESH: France / epidemiology, education.field_of_study, Incidence (epidemiology), 3. Good health, MESH: COVID-19 / epidemiology, Nephrology, Hemodialysis, medicine.medical_specialty, Population, Lower risk, Article, 03 medical and health sciences, MESH: Sex Factors, Internal medicine, medicine, MESH: SARS-CoV-2, MESH: Renal Dialysis / statistics & numerical data, education, Dialysis, Vascular disease, business.industry, medicine.disease, Former Smoker, MESH: Critical Care / statistics & numerical data, 030104 developmental biology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Home, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, MESH: Hemodialysis, Home / statistics & numerical data
Abstract: The aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed., Graphical abstract
Published: 2020
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36. Management of digestive cancers during the COVID-19 second wave: A French intergroup point of view (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, SFR)

Author: Florence Huguet, Olivier Bouché, Astrid Lièvre, Pierre Michel, Sébastien Gaujoux, Léon Maggiori, Pascale Mariani, David Tougeron, Côme Lepage, Thierry Lecomte, Michel Ducreux, Christophe Louvet, Boris Guiu, Thomas Aparicio, Jonchère, Laurent, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Institut Gustave Roussy (IGR), Département de médecine oncologique [Gustave Roussy], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), CHU Tenon [AP-HP], Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut Mutualiste de Montsouris (IMM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Curie [Paris], Centre Hospitalier Universitaire de Reims (CHU Reims), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, Biomedical Research, SFED, SFCD, Digestive cancer, GERCOR, [SDV.CAN]Life Sciences [q-bio]/Cancer, Context (language use), Antineoplastic Agents, French Clinical Practice Guidelines, Digestive System Neoplasms, 03 medical and health sciences, SFR, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Multidisciplinary approach, Cancer screening, Pandemic, medicine, FFCD, Humans, Chemotherapy, UNICANCER, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, Digestive System Surgical Procedures, Early Detection of Cancer, SFRO, Cancer prevention, Hepatology, Radiotherapy, SNFGE, business.industry, SARS-CoV-2, Gastroenterology, Cancer, COVID-19, Evidence-based medicine, medicine.disease, ACHBT, 3. Good health, COVID-19 infection, Clinical trial, 030220 oncology & carcinogenesis, Guidelines Update, 030211 gastroenterology & hepatology, Surgery, France, business
Abstract: Introduction The COVID-19 pandemic has major impact of healthcare systems, including cancer care pathways. The aim of this work is to discuss in a multidisciplinary approach the therapeutic and/or strategies adaptations for patients treated for a digestive cancer during the European second wave of COVID-19 pandemic. Methods A collaborative work was performed by several French societies to answer how to preserve digestive cancer care with no loss of chance during the second wave of COVID-19. In this context, all recommendations are graded as expert’s agreement according to level evidence found in literature until October 2020 and the experience of the first wave of the COVID-19 pandemic. Results As far as possible, no therapeutic modification should be carried out. If necessary, therapeutic adjustments may be considered if they do not constitute a loss of chance for patients. Considering the level of evidence all therapeutic modifications need to be discussed in multidisciplinary tumor board meeting and with patient consent. By contrast to first wave cancer prevention, cancer screening, supportive care and clinical trials should be continued. Conclusion Recommendations proposed could limit cancer excess mortality due to the COVID-19 pandemic but should be adapted according to the situation in each hospital.
Published: 2020
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37. Bariatric Surgery Provides Long-term Resolution of Nonalcoholic Steatohepatitis and Regression of Fibrosis

Author: Sébastien Dharancy, Hélène Verkindt, V. Raverdy, Philippe Mathurin, Line-Carolle Ntandja-Wandji, Guillaume Lassailly, François Pattou, Massih Ningarhari, Robert Caiazzo, Viviane Gnemmi, Alexandre Louvet, Gregory Baud, Emmanuelle Leteurtre, Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Recherche translationnelle sur le diabète - U 1190 (RTD), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CCSD, Accord Elsevier, ANR-16-RHUS-0006,PreciNASH,PreciNASH(2016), and Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC))
Subjects: Liver Cirrhosis, Male, Time Factors, Biopsy, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Bariatric Surgery, Single Center, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Fibrosis, Interquartile range, Weight loss, Nonalcoholic fatty liver disease, Prospective Studies, Prospective cohort study, 2. Zero hunger, 0303 health sciences, Roux-en-Y-Gastric-Bypass, Remission Induction, Gastroenterology, Middle Aged, Sleeve Gastrectomy, Obesity, Morbid, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Liver, Female, 030211 gastroenterology & hepatology, France, medicine.symptom, Adult, medicine.medical_specialty, Sleeve gastrectomy, Gastric Bypass, digestive system, 03 medical and health sciences, Gastric Banding, Weight Loss, medicine, Humans, 030304 developmental biology, Hepatology, business.industry, medicine.disease, digestive system diseases, Surgery, business, Body mass index, Follow-Up Studies
Abstract: International audience; Background and aims: Studies are needed to determine the long-term effects of bariatric surgery for patients with nonalcoholic steatohepatitis (NASH). We evaluated sequential liver samples, collected the time of bariatric surgery and 1 and 5 years later, to assess the long-term effects of bariatric surgery in patients with NASH.Methods: We performed a prospective study of 180 severely obese patients with biopsy-proven NASH, defined by the NASH clinical research network histologic scores. The patients underwent bariatric surgery at a single center in France and were followed for 5 years. We obtained liver samples from 125 of 169 patients (76%) having reached 1 year and 64 of 94 patients (68%) having reached 5 years after surgery. The primary endpoint was the resolution of NASH without worsening of fibrosis at 5 years. Secondary end points were improvement in fibrosis (reduction of ≥1 stage) at 5 years and regression of fibrosis and NASH at 1 and 5 years.Results: At 5 years after bariatric surgery, NASH was resolved, without worsening fibrosis, in samples from 84% of patients (n = 64; 95% confidence interval, 73.1%-92.2%). Fibrosis decreased, compared with baseline, in samples from 70.2% of patients (95% CI, 56.6%-81.6%). Fibrosis disappeared from samples from 56% of all patients (95% CI, 42.4%-69.3%) and from samples from 45.5% of patients with baseline bridging fibrosis. Persistence of NASH was associated with no decrease in fibrosis and less weight loss (reduction in body mass index of 6.3 ± 4.1 kg/m2 in patients with persistent NASH vs reduction of 13.4 ± 7.4 kg/m2; P = .017 with resolution of NASH). Resolution of NASH was observed at 1 year after bariatric surgery in biopsies from 84% of patients, with no significant recurrence between 1 and 5 years (P = .17). Fibrosis began to decrease by 1 year after surgery and continued to decrease until 5 years (P < .001).Conclusions: In a long-term follow-up of patients with NASH who underwent bariatric surgery, we observed resolution of NASH in liver samples from 84% of patients 5 years later. The reduction of fibrosis is progressive, beginning during the first year and continuing through 5 years.
Published: 2020
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38. Understanding the Prognostic Value of Primary Tumor Location and KRAS in Metastatic Colorectal Cancer: A Post Hoc Analysis of the OPTIMOX3 DREAM Phase III Study

Author: Christophe Tournigand, Benoist Chibaudel, Thierry André, Magdalena Benetkiewicz, Annette K. Larsen, Christophe Louvet, Aimery de Gramont, 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), Hôpital Cognacq-Jay, Institut Universitaire de Cancérologie [Paris] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mutualiste de Montsouris (IMM), Cooperator Multidisciplinary Oncology Group (GERCOR), CCSD, Accord Elsevier, 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], 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: Male, Oncology, right-sided, Colorectal cancer, [SDV]Life Sciences [q-bio], Kaplan-Meier Estimate, medicine.disease_cause, predictive factor, sidedness, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Cecum, left-sided, Gastroenterology, Prognosis, Primary tumor, anti-EGFR, Progression-Free Survival, 3. Good health, ErbB Receptors, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, KRAS, Colorectal Neoplasms, medicine.medical_specialty, Colon, Anemia, Rectum, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, Growth factor receptor, Predictive Value of Tests, Internal medicine, Post-hoc analysis, medicine, Humans, neoplasms, Aged, Retrospective Studies, Splenic flexure, business.industry, medicine.disease, digestive system diseases, Feasibility Studies, business
Abstract: International audience; Introduction: We evaluated the prognostic value of KRAS and primary tumor location (PTL) for overall survival (OS), progression-free survival (PFS), and post-progression survival (PPS) in metastatic colorectal cancer (mCRC).Material and methods: Individual patient data from the DREAM phase III study were retrospectively analyzed. PTL was defined as right-sided or left-sided if tumor arising from the cecum to transverse colon or from the splenic flexure to the rectum, respectively. OS, PFS, and PPS were estimated using the Kaplan-Meier method and compared using log-rank test.Results: Among 700 patients included in the DREAM study, both PTL and KRAS were available for 536 (76.6%) patients. PTL showed stronger prognostic impact than KRAS status for OS (HRPTL, 1.62 vs. HRKRAS, 1.37), PFS (HRPTL, 1.27 vs. HRKRAS, 1.15) and PPS (HRPTL, 1.54 vs. HRKRAS, 1.33). Interaction between PTL and KRAS was significant (Pinteraction = .003). A negative impact of KRAS mutation was observed for OS and PPS, but not for PFS. Right-sided tumor was associated with poorer Eastern Cooperative Oncology Group performance status, anemia, and KRAS mutation, whereas left-sided KRAS wild-type tumor was associated with an increased lactate dehydrogenase. In patients with KRAS mutant mCRC, alkaline phosphatase was the main prognostic factor whatever the tumor site, whereas in those with KRAS wild-type tumors, prognostic factors varied according to PTL. The exposition to the anti-epidermal growth factor receptor (anti-EGFR) agents during and after study was similar in patients with left-sided and right-sided KRAS wild-type tumors.Conclusion: Our findings suggest that a better prognosis of patients with mCRC with left-sided tumors is driven more strongly by PPS than by PFS when compared with patients with right-sided tumors, whatever the KRAS mutation status. This phenomenon was independent from the exposition to poststudy anti-EGFR monoclonal antibody.
Published: 2020
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39. Unexpected benefits of the COVID challenge: When critically ill adult patients are managed in a pediatric PACU

Author: Yael Levy, Nada Sabourdin, Nicolas Louvet, Sarah Chemam, Marie-Pierre Bonnet, Isabelle Constant, Service de réanimation néonatale et pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service d'anesthésie-réanimation [CHU Trousseau], Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Lallemant, Christopher
Subjects: Adult, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Critical Illness, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MEDLINE, 030204 cardiovascular system & hematology, Pacu, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, 0302 clinical medicine, Correspondence, Humans, Medicine, 030212 general & internal medicine, Pediatrics, Perinatology, and Child Health, Child, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, biology, Adult patients, SARS-CoV-2, business.industry, Critically ill, COVID-19, biology.organism_classification, 3. Good health, Anesthesiology and Pain Medicine, Pediatrics, Perinatology and Child Health, business
Abstract: International audience
Published: 2020
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40. A tool to predict progression of non-alcoholic fatty liver disease in severely obese patients

Author: Deuffic-Burban, Sylvie, Bauvin, Pierre, Delacôte, Claire, Lassailly, Guillaume, Ntandja Wandji, Line Carolle, Gnemmi, Viviane, Dautrecque, Flavien, Louvet, Alexandre, Caiazzo, Robert, Raverdy, Violeta, Leteurtre, Emmanuelle, Pattou, François, Deuffic‐Burban, Sylvie, Mathurin, Philippe, 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 des Maladies de l'Appareil Digestif et de la Nutrition [CHRU Lille], Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Recherche translationnelle sur le diabète - U 1190 (RTD), 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), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, This work is supported by the French government, managed by the National Research Agency (ANR) under the Future Investment Program (PIA2) with the reference ANR-16-RHUS-0006_PreciNASH., ANR-16-RHUS-0006,PreciNASH,PreciNASH(2016), CHU Lille, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Bauvin, Pierre, PreciNASH - - PreciNASH2016 - ANR-16-RHUS-0006 - RHUS - VALID, Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Genomic Institute for Diabetes - FR 3508 (EGID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Deuffic-Burban, Sylvie
Subjects: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Biopsy, Population, Bariatric Surgery, Disease, Overweight, 03 medical and health sciences, Liver disease, 0302 clinical medicine, disease progression, Non-alcoholic Fatty Liver Disease, Diabetes mellitus, Internal medicine, medicine, Humans, risk factors, Obesity, education, ComputingMilieux_MISCELLANEOUS, education.field_of_study, Hepatology, business.industry, Fatty liver, fibrosis, NASH, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Markov model, 3. Good health, Liver, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, medicine.symptom, Steatohepatitis, business
Abstract: International audience; Background & aims: Severely obese patients are a growing population at risk of non-alcoholic fatty liver disease (NAFLD). Considering the increasing burden, a predictive tool of NAFLD progression would be of interest. Our objective was to provide a tool allowing general practitioners to identify and refer the patients most at risk, and specialists to estimate disease progression and adapt the therapeutic strategy.Methods: This predictive tool is based on a Markov model simulating steatosis, fibrosis and non-alcoholic steatohepatitis (NASH) evolution. This model was developped from data of 1801 severely obese, bariatric surgery candidates, with histological assessment, integrating duration of exposure to risk factors. It is then able to predict current disease severity in the absence of assessment, and future cirrhosis risk based on current stage.Results: The model quantifies the impact of sex, body-mass index at 20, diabetes, age of overweight onset, on progression. For example, for 40-year-old severely obese patients seen by the general practitioners: (a) non-diabetic woman overweight at 20, and (b) diabetic man overweight at 10, without disease assessment, the model predicts their current risk to have NASH or F3-F4: for (a) 5.7% and 0.6%, for (b) 16.1% and 10.0% respectively. If those patients have been diagnosed F2 by the specialist, the model predicts the 5-year cirrhosis risk: 1.8% in the absence of NASH and 6.0% in its presence for (a), 10.3% and 26.7% respectively, for (b).Conclusions: This model provides a decision-making tool to predict the risk of liver disease that could help manage severely obese patients.
Published: 2020
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41. Predictive Value of Neutrophils Count for Local Tumor Control After Chemoradiotherapy in Patients With Locally Advanced Pancreatic Carcinoma

Author: Franck Bonnetain, Antoine Schernberg, Paul Van Houtte, Pascal Hammel, Jean-Luc Van Laethem, Florence Huguet, Dewi Vernerey, Bengt Glimelius, Christophe Louvet, and David Goldstein
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Neutrophils, medicine.medical_treatment, Gastroenterology, Disease-Free Survival, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Leukocyte Count, 0302 clinical medicine, Predictive Value of Tests, Internal medicine, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Aged, Chemotherapy, Radiation, business.industry, Proportional hazards model, Induction chemotherapy, Chemoradiotherapy, Middle Aged, Neutrophilia, Pancreatic Neoplasms, Oncology, 030220 oncology & carcinogenesis, Predictive value of tests, Absolute neutrophil count, Biomarker (medicine), Female, medicine.symptom, business
Abstract: Purpose Baseline neutrophil count may predict overall survival (OS) in patients with locally advanced pancreatic cancer (LAPC). Methods and Materials The international multicenter randomized LAP07 phase 3 trial has enrolled 442 patients with LAPC. We analyzed the prognostic value of both baseline neutrophilia (neutrophil count >7 g/L) and elevated or increasing neutrophil count as (1) neutrophilia or (2) increased absolute neutrophil count after induction chemotherapy versus baseline for OS, progression-free survival, and local control (LC). A Cox proportional hazard model was used to assess elevated or increasing neutrophil count status by randomly assigned treatment interactions for each endpoint. Results Among the 442 patients, 47 patients (11%) with baseline neutrophilia had worse OS (median 8.9 vs 13.3 months; P = .01). After induction chemotherapy, among the 235 patients whose blood counts were available, 90 patients (38%) had elevated or increasing neutrophil count associated with poorer OS in univariate (median 14.4 vs 17.9 months; P = .001) and multivariate analysis (P = .004). Elevated or increasing neutrophil count was also predictive of a decreased benefit of chemoradiation therapy on LC. In 126 patients without elevated or increasing neutrophil count, 1-year LC was 80% in the chemoradiation arm versus 54% in the chemotherapy arm (P Conclusions In this study, baseline neutrophilia and increased absolute neutrophil count were associated with worse OS in this large series of patients with LAPC. In addition, the counts were an independent prognosis factor and a strong predictive LC biomarker for chemoradiation therapy benefit. An assessment of neutrophils counts can help to improve the selection of patients who might benefit from chemoradiation therapy after induction chemotherapy.
Published: 2020

42. Adipose Tissue Properties in Tumor-Bearing Breasts

Author: Isabelle Miran, Dominique Scherer, Pauline Ostyn, Chafika Mazouni, Françoise Drusch, Marine Bernard, Emilie Louvet, Julien Adam, Marie-Christine Mathieu, Mariam Haffa, Jean-Philippe Antignac, Bruno Le Bizec, Philippe Vielh, Philippe Dessen, Hervé Perdry, Suzette Delaloge, Jean Feunteun, L'HOSTIS, Dominique, Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Center for Tumor Diseases [Dresden] (NCT), Technische Universität Dresden = Dresden University of Technology (TU Dresden)-German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)-Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Medical Biometry and Informatics [Heidelberg], Universität Heidelberg [Heidelberg], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Intégrité du génome et cancers (IGC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay, Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Génétique [Villejuif], Institut Gustave Roussy (IGR), Odyssea Paris (JF, SD)., PO was supported by a postdoctoral grant from Fondation pour la Recherche Médicale #FRM:SPF20170938649., Gustave Roussy (Villejuif) and DKFZ (Heidelberg) provided intramural funding., Institut Gustave Roussy (IGR)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), and Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0301 basic medicine, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Cancer Research, Pathology, medicine.medical_specialty, Integrin, permissive cancer niche, Adipose tissue, [SDV.CAN]Life Sciences [q-bio]/Cancer, Inflammation, Biology, lcsh:RC254-282, 03 medical and health sciences, breast cancer, 0302 clinical medicine, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Stroma, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, non-cell autonomous, Interleukin 8, skin and connective tissue diseases, Original Research, IL-8, Wnt signaling pathway, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, adipose tissue, 030104 developmental biology, Oncology, Tumor progression, 030220 oncology & carcinogenesis, biology.protein, medicine.symptom
Abstract: International audience; The tissue stroma plays a major role in tumors' natural history. Most programs for tumor progression are not activated as cell-autonomous processes but under the conditions of cross-talks between tumor and stroma. Adipose tissue is a major component of breast stroma. This study compares adipose tissues in tumor-bearing breasts to those in tumor-free breasts with the intention of defining a signature that could translate into markers of cancer risk. In tumor-bearing breasts, we sampled adipose tissues adjacent to, or distant from the tumor. Parameters studied included: adipocytes size and density, immune cell infiltration, vascularization, secretome and gene expression. Adipose tissues from tumor-bearing breasts, whether adjacent to or distant from the tumor, do not differ from each other by any of these parameters. By contrast, adipose tissues from tumor-bearing breasts have the capacity to secrete twice as much interleukin 8 (IL-8) than those from tumor-free breasts and differentially express a set of 137 genes of which a significant fraction belongs to inflammation, integrin and wnt signaling pathways. These observations show that adipose tissues from tumor-bearing breasts have a distinct physiological status from those from tumor-free breasts. We propose that this constitutive status contributes as a non-cell autonomous process to determine permissiveness for tumor growth.
Published: 2020
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43. Sirtuin 1 deficiency decreases bone mass and increases bone marrow adiposity in a mouse model of chronic energy deficiency

Author: Olfa Ghali Mhenni, Damien Leterme, Loïc Louvet, Pierre Hardouin, Pierre Marchandise, Christophe Chauveau, Véronique Gauthier, Séverine Delplace, Flore Miellot, Marrow Adiposity & Bone Lab - Adiposité Médullaire et Os - ULR 4490 (MABLab (ex-pmoi)), Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and Université du Littoral Côte d'Opale (ULCO)
Subjects: 0301 basic medicine, medicine.medical_specialty, lcsh:Diseases of the musculoskeletal system, Histology, Stromal cell, Physiology, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], 030209 endocrinology & metabolism, FOXO1, Resveratrol, Mice, chemistry.chemical_compound, 03 medical and health sciences, 0302 clinical medicine, Sirtuin 1, Bone Marrow, Osteogenesis, Internal medicine, medicine, Animals, Orthopedics and Sports Medicine, Adiposity, 0303 health sciences, Adipogenesis, Osteoblasts, biology, Chemistry, food and beverages, Cell Differentiation, Osteoblast, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, 030301 anatomy & morphology, Sirtuin, biology.protein, Female, Bone marrow, lcsh:RC925-935, Stem cell, hormones, hormone substitutes, and hormone antagonists
Abstract: International audience; Sirtuin of type 1 (Sirt1), a class III HDAC, is known to be involved in the regulation of differentiation of skeletal stem cells (SSCs) into osteoblasts and adipocytes. In caloric restriction, it has been shown that the expression and activity of Sirt1 is a tissue-dependent regulation. However, at present, no study has focused on the link between Sirt1, bone marrow adiposity (BMA) and osteoporosis related to anorexia nervosa (AN). Thus, the aims of this work were to (i) determine BMA and bone changes in a mouse model replicating the phenotypes of AN (separation-based anorexia model (SBA)); (ii) determine the expression of Sirt1 in bone marrow stromal cells (BMSCs) extracted from these mice and identify their differentiation capacities; (iii) study the effects of pharmacological activation and inhibition of Sirt1 on the osteoblastogenesis and adipogenesis of these cells and (iiii) delineate the molecular mechanism by which Sirt1 could regulate osteogenesis in an SBA model. Our results demonstrated that SBA protocol induces an increase in BMA and alteration of bone architecture. In addition, BMSCs from restricted mice present a down-regulation of Sirt1 which is accompanied by an increase in adipogenesis at expense of osteogenesis. After a 10-day organotypic culture, tibias from SBA mice displayed low levels of Sirt1 mRNA which are restored by resveratrol treatment. Interestingly, this recovery of Sirt1 levels also returned the BMA, BV/TV and Tb.Th in cultured tibias from SBA mice to normal levels. In contrast of down-regulation of Sirt1 expression induced by sirtinol treatment, stimulation of Sirt1 expression by resveratrol lead to a decrease in adipogenesis and increase in osteogenesis. Finally, to investigate the molecular mechanisms by which Sirt1 could regulate osteogenesis in the SBA model, the acetylation levels of Runx2 and Foxo1 transcription factors were determined. Our data show that this chronic energy deficiency in female mice causes a decrease in BMSC activity, resulting in critical changes to Runx2 and Foxo1 acetylation levels and thus to their activity. Altogether, these data suggest that Sirt1 could be considered as a potential therapeutic target in osteoporosis related to AN.
Published: 2020
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44. IL-33/ST2 pathway regulates neutrophil migration and predicts outcome in patients with severe alcoholic hepatitis

Author: Sébastien Dharancy, Line-Carolle Ntandja-Wandji, Philippe Mathurin, Ramon Bataller, Julie Demaret, Doumet Georges Helou, Massih Ningarhari, Elodie Drumez, Emilie Gantier, Axel Périanin, Laurent Dubuquoy, Florent Artru, François Maggiotto, Sylvie Chollet-Martin, Jean-Paul Pais de Barros, Guillaume Lassailly, Julien Labreuche, Mohammed Bou Saleh, Alexandre Louvet, Université de Lille, Inserm, CHU Lille, Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286, Lille Inflammation Research International Center - U 995 [LIRIC], METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694, Institute for Translational Research in Inflammation - U 1286 [INFINITE (Ex-Liric)], Equipe LIPNESS (LNC - U1231) [LIPNESS], Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS], Université Paris Saclay (COmUE), Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)], AP-HP - Hôpital Bichat - Claude Bernard [Paris], University of Pittsburgh [PITT], Université de Lille, LillOA, 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), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Equipe LIPNESS (LNC - U1231) (LIPNESS), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-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) (AP-HP), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), 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, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)
Subjects: Male, 0301 basic medicine, Alcoholic liver disease, Cirrhosis, Polymorphonuclear neutrophils, Neutrophils, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Apoptosis, Gastroenterology, Receptors, Interleukin-8B, Liver disease, 0302 clinical medicine, Cell Movement, Liver Cirrhosis, Alcoholic, Prospective Studies, CXC chemokine receptors, Receptor, Cells, Cultured, Migration, Middle Aged, Prognosis, Recombinant Proteins, 3. Good health, Alcoholic hepatitis, Infection, Interleukin-33, Female, 030211 gastroenterology & hepatology, Signal Transduction, Adult, medicine.medical_specialty, Sepsis, 03 medical and health sciences, Internal medicine, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, cardiovascular diseases, Aged, Hepatology, Hepatitis, Alcoholic, business.industry, medicine.disease, Interleukin-1 Receptor-Like 1 Protein, nervous system diseases, Interleukin 33, 030104 developmental biology, Case-Control Studies, business, Follow-Up Studies
Abstract: Background & Aims Severe alcoholic hepatitis (SAH) is associated with a high risk of infection. The IL-33/ST2 pathway is involved in sepsis control but data regarding its role in alcohol-related liver disease (ALD) are lacking. We aimed to characterize the role of IL-33/ST2 in the polymorphonuclear neutrophils (PMNs) of patients with ALD and SAH. Methods Serum and circulating neutrophils were collected from patients with SAH, alcoholic cirrhosis and healthy controls. We quantified IL-33/ST2 pathway activity and CXCR2 at baseline and after exposure to IL-33. We also determined the migration capacity of PMNs. Results The decoy receptor of IL-33 (soluble ST2 [sST2]) was increased in SAH vs. cirrhosis and controls, demonstrating the defect in this pathway during ALD. The sST2 level was associated with response to treatment, 2-month survival, infection-free survival and probability of infection in SAH. Endotoxemia was weakly correlated with sST2. GRK2, a negative regulator of CXCR2, was overexpressed in PMNs of patients with SAH and cirrhosis and was decreased by IL-33. CXCR2 levels on PMNs were lower in SAH vs. cirrhosis and controls. Treatment with IL-33 partially restored CXCR2 expression in SAH and cirrhosis. PMN migration upon IL-8 was lower in patients with SAH and cirrhosis vs. controls. Treatment with IL-33 partially restored migration in those with SAH and cirrhosis. Interestingly, the migration capacity of PMNs and the response to IL-33 were enhanced in responders to corticosteroids (Lille Conclusion The IL33/ST2 pathway is defective in SAH and predicts outcome. This defect is associated with decreased CXCR2 expression on the surface of PMNs and lower migration capacity, which can be corrected by IL-33, especially in patients responding to steroids. These results suggest that IL-33 has therapeutic potential for SAH and its infectious complications. Lay summary The neutrophils of patients with severe alcoholic hepatitis are associated with a defect in the IL-33/ST2 pathway. This defect is associated with lower migration capacities in neutrophils and a higher probability of getting infected. Administration of IL-33 to the neutrophils at least partly restores this defect and may be effective at reducing the risk of infection in patients with severe alcoholic hepatitis.
Published: 2020
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45. Uremic Toxins and Vascular Dysfunction

Author: Gaëlle Lenglet, Sophie Liabeuf, Nadia Flissi, Marlène Gallet, Ziad A. Massy, Saïd Kamel, Isabelle Six, Loïc Louvet, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), and Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie
Subjects: medicine.medical_specialty, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], uremic toxins, lcsh:Medicine, Inflammation, Review, 030204 cardiovascular system & hematology, Sulfuric Acid Esters, Toxicology, medicine.disease_cause, Nitric oxide, 03 medical and health sciences, chemistry.chemical_compound, Cresols, 0302 clinical medicine, Internal medicine, medicine, Animals, Humans, In patient, Vascular Diseases, Risk factor, Renal Insufficiency, Chronic, 030304 developmental biology, Uremia, 0303 health sciences, business.industry, lcsh:R, vascular dysfunction, medicine.disease, Keywords: chronic kidney disease, Pathophysiology, 3. Good health, Fibroblast Growth Factor-23, Oxidative Stress, Endocrinology, chemistry, Uremic toxins, Blood Vessels, medicine.symptom, Inflammation Mediators, business, Indican, Oxidative stress, chronic kidney disease, Kidney disease
Abstract: International audience; Vascular dysfunction is an essential element found in many cardiovascular pathologies and in pathologies that have a cardiovascular impact such as chronic kidney disease (CKD). Alteration of vasomotricity is due to an imbalance between the production of relaxing and contracting factors. In addition to becoming a determining factor in pathophysiological alterations, vascular dysfunction constitutes the first step in the development of atherosclerosis plaques or vascular calcifications. In patients with CKD, alteration of vasomotricity tends to emerge as being a new, less conventional, risk factor. CKD is characterized by the accumulation of uremic toxins (UTs) such as phosphate, para-cresyl sulfate, indoxyl sulfate, and FGF23 and, consequently, the deleterious role of UTs on vascular dysfunction has been explored. This accumulation of UTs is associated with systemic alterations including inflammation, oxidative stress, and the decrease of nitric oxide production. The present review proposes to summarize our current knowledge of the mechanisms by which UTs induce vascular dysfunction.
Published: 2020
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46. Alcohol‐Related Liver Disease: Areas of Consensus, Unmet Needs and Opportunities for Further Study†

Author: Szabo, Gyongyi, Kamath, Patrick S., Shah, Vijay H., Thursz, Mark, Mathurin, Philippe, EASL-AASLD Joint Meeting (Addolorato, G, Bataller, R, Burra, P, Castera, L, Cortez Pinto, H, Diehl, Am, Gao, B, Gilmore, Si, Hampe, J, Jürgen, R, Karin, M, Krag, A, Leon, D, Leptak, C, Louvet, A, Lucey, M, Mcclain, C, Nagy, L, Pageaux, Gp, Sanyal, A, Schnabl, B, Tiniakos, D, Trautwein, C, and Tsukamoto, H. ).
Subjects: 0301 basic medicine, medicine.medical_specialty, Alcoholic liver disease, Hepatology, business.industry, MEDLINE, Context (language use), Disease, medicine.disease, 03 medical and health sciences, Liver disease, 030104 developmental biology, 0302 clinical medicine, Epidemiology, medicine, 030211 gastroenterology & hepatology, Translational science, Disease management (health), Intensive care medicine, business
Abstract: A joint meeting of the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD) was held in London on September 30 and October 1, 2017. The goals of the meeting were to identify areas of broad agreement and disagreement, develop consensus, and determine future directions to ultimately reduce the burden, morbidity, and mortality of alcohol-related liver disease (previously termed alcoholic liver disease). The specific aims of the meeting were to identify unmet needs and areas for future investigation, in order to reduce alcohol consumption, develop markers for diagnosis and prognosis of disease, and create a framework to test novel pharmacological agents with pre-specified treatment endpoints. A table summary of these goals and aims is provided in the context of epidemiology, current management strategies, next steps for future trials and translational science.
Published: 2019
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47. Oxaliplatin, 5-Fluorouracil and Nab-paclitaxel as perioperative regimen in patients with resectable gastric adenocarcinoma: A GERCOR phase II study (FOXAGAST)

Author: C. de la Fouchardiere, Aurélia Meurisse, Jean-Marc Ferraz, Magali Svrcek, J-B. Bachet, C. Louvet, Romain Cohen, Sarah Watson, Christophe Tournigand, Marine Lefevre, Stefano Kim, and Delphine Colin
Subjects: Male, 0301 basic medicine, Cancer Research, medicine.medical_specialty, Paclitaxel, medicine.medical_treatment, Phases of clinical research, Adenocarcinoma, Neutropenia, Gastroenterology, Perioperative Care, 03 medical and health sciences, 0302 clinical medicine, FOLFOX, Stomach Neoplasms, Albumins, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Aged, Aged, 80 and over, Chemotherapy, business.industry, Perioperative, Middle Aged, Prognosis, medicine.disease, Oxaliplatin, Survival Rate, Regimen, 030104 developmental biology, Oncology, Fluorouracil, 030220 oncology & carcinogenesis, Female, business, Follow-Up Studies, medicine.drug
Abstract: Background 5-Fluorouracil (5-FU) and platinum-based perioperative chemotherapy is standard of care for resectable gastric adenocarcinoma (RGA). Nanoparticle albumin-bound (Nab-) paclitaxel is active in advanced disease but has never been evaluated in the perioperative setting. The objective was to evaluate the efficacy of Nab-paclitaxel in combination with FOLFOX for RGA patients. Methods We performed a non-randomised, open-label, phase II study. RGA patients were assigned to receive neoadjuvant Nab-paclitaxel (150 mg/m2) and FOLFOX q2w for six cycles. Six additional post-operative cycles were kept at the investigator's discretion. The primary end-point was complete pathological response (tumour regression grade [TRG1]) rate. According to Fleming design, 49 patients were required to test H0 (10% TRG1) and H1 (25% TRG1). To reject H0, TRG1 had to be achieved in 8 patients. Results Forty-nine patients were included. Median number of neoadjuvant chemotherapy cycles was 6 (range, 3–6). Median dose intensity for Nab-paclitaxel, oxaliplatin and 5-FU was 96% (38–103%), 97% (47–103%) and 99% (50–112%), respectively. Surgery could not be performed in 5 (10.2%) patients. Tumour resection was R0 for 42 of 44 (95.5%) patients. Pathological review classified tumours as TRG1 to TRG5 for 8 (16.3%), 11 (22.5%), 4 (8.2%), 18 (36.7%) and 3 (6.1%) patients, respectively. Grade 3 or worse toxicities during neoadjuvant chemotherapy were non-febrile neutropenia (20.4%), nausea (8.2%), diarrhoea (8.2%) and neuropathy (6.1%). Of 44 patients, 14 (31.8%) experienced surgery-related complications and three (6.8%) died of surgical complications. Conclusion This regimen shows promising activity. Toxicity is manageable but a meaningful rate of surgical complications was observed. This strategy deserves investigation in phase III studies.
Published: 2019
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48. Trans-catheter aortic valve replacement (tavr) as bridge therapy restoring eligibility for liver transplantation in cirrhotic patients

Author: Mehdi El Amrani, Massih Ningarhari, Guillaume Millet, Sébastien Dharancy, Flavien Vincent, Thibault Meurice, Cedric Delhaye, Guillaume Lassailly, Stéphanie Truant, François-René Pruvot, Clementine Levy, Gilles Lebuffe, Emmanuel Boleslawski, Philippe Mathurin, Alexandre Louvet, CIC CHU ( Lille)/inserm, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - UAR 3290 (MSAP), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Coeur Poumon [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), and Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: Liver Cirrhosis, medicine.medical_specialty, Heart disease, medicine.medical_treatment, [SDV]Life Sciences [q-bio], heart disease, 030230 surgery, Liver transplantation, comorbidities, Severity of Illness Index, Organ transplantation, Transcatheter Aortic Valve Replacement, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Aortic valve replacement, Valve replacement, Risk Factors, cardiovascular disease, medicine, Humans, Immunology and Allergy, Pharmacology (medical), Contraindication, Transplantation, liver transplantation, business.industry, cirrhosis, Aortic Valve Stenosis, medicine.disease, practice, Surgery, Stenosis, Treatment Outcome, clinical research, Aortic Valve, hepatology, cardiovascular system, business, liver disease
Abstract: International audience; Severe aortic stenosis is a widespread valve disease, constituting a contraindication to organ transplantation due to cardiovascular morbidity and projected mortality. Mortality after conventional surgical aortic valve replacement in cirrhotic patients depends upon the Child-Pugh class. In the past few years, transcatheter aortic valve replacement has progressively become the treatment of choice for high-risk patients with severe aortic stenosis. Here, we report the cases of 3 cirrhotic patients who became eligible for liver transplantation after successful transcatheter aortic valve replacement as bridge therapy.
Published: 2020
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49. Drastic Reduction of Turnaround Time After Implementation of a Fully Automated Assay for RAS-BRAF Mutations in Colorectal Cancer: A Pilot Prospective Study in Real-life Conditions

Author: Maryline Dorel, Simon Triby, Angélique Guillaudeau, Evelyne Maillet, Stéphane Rossat, Daniel Vacque, Nathalie Le Berre, Marine Lefevre, Dominique Genet, Jean-Christophe Sabourin, Christophe Louvet, Jérôme Chamois, and Hervé Perrier
Subjects: 0301 basic medicine, Oncology, Neuroblastoma RAS viral oncogene homolog, Proto-Oncogene Proteins B-raf, Cancer Research, medicine.medical_specialty, Time Factors, Colorectal cancer, DNA Mutational Analysis, Pilot Projects, medicine.disease_cause, Turnaround time, Pathology and Forensic Medicine, GTP Phosphohydrolases, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, Automation, 0302 clinical medicine, Internal medicine, medicine, In real life, Humans, Multiplex, Prospective Studies, Pathology, Molecular, Prospective cohort study, business.industry, Membrane Proteins, General Medicine, medicine.disease, 030104 developmental biology, Fully automated, 030220 oncology & carcinogenesis, Mutation, KRAS, business, Colorectal Neoplasms
Abstract: In some situations, there is a need for rapid mutation tests for guiding clinical decisions and starting targeted therapies with minimal delays. In this study we evaluated the turnaround time before and after the implementation of a fully automated multiplex assay for KRAS and NRAS/BRAF mutation tests (Idylla™ platform, Biocartis) in metastatic colorectal cancer. The objective of this project was to compare the turnaround times in 2017–2018 with the fully automated multiplex assay to the 2016 results with previous methods. Centers with a number of tests for metastatic colorectal cancer > 100 yearly and a usual turnaround time ≥ 3 weeks for mutation detection were selected. Results of 505 KRAS tests and 369 NRAS/BRAF tests were transmitted by 10 centers. The mean turnaround time from test prescription to reception of results was reduced from 25.8 days in 2016 to 4.5 days in 2017–2018. In conclusion, this pilot project shows that the Idylla™ platform for testing KRAS and NRAS/BRAF mutations allows an optimized turnaround time from test prescription to reception of results.
Published: 2020

50. Grand Rounds: Alcoholic Hepatitis

Author: Alexandre Louvet, Patrick S. Kamath, Ashwani K. Singal, and Vijay H. Shah
Subjects: 0301 basic medicine, medicine.medical_specialty, Alcoholic liver disease, Biopsy, medicine.medical_treatment, Alcoholic hepatitis, Liver transplantation, Severity of Illness Index, Article, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Internal medicine, medicine, Humans, Glucocorticoids, First episode, Hepatology, medicine.diagnostic_test, Hepatitis, Alcoholic, business.industry, Jaundice, Prognosis, medicine.disease, Liver Transplantation, Alcoholism, 030104 developmental biology, Liver, Liver biopsy, Prednisolone, 030211 gastroenterology & hepatology, medicine.symptom, business, medicine.drug
Abstract: Clinical vignette A 33-year-old Caucasian male was admitted to hospital with recent onset of jaundice of 2–3 weeks duration. He reported heavy use of alcohol for the last 10 years with the last drink a day prior to the onset of symptoms. At admission, he was alert and oriented to time, place, and person, and was deeply jaundiced. His laboratory profile can be summarised as follows: haemoglobin 12.1 g/dl, white blood cell count 18,700 with 81% neutrophils, serum bilirubin 33 (direct 22) mg/dl, aspartate aminotransferase 147 IU/L, alanine aminotransferase 62 IU/L, alkaline phosphatase 117 IU/L, serum albumin 2.8 gm/dl, serum creatinine 0.6 mg/dl, prothrombin time 18.3 (control 14.5) seconds, and international normalized ratio 1.48. He was diagnosed with severe alcoholic hepatitis (Maddrey discriminant function score of 50) and treated with prednisolone for 28 days with symptomatic and biochemical improvement. His Lille score at seven days was 0.4, and his serum bilirubin had decreased to 3.5 mg/dl at the end of treatment. He was also seen by the addiction team during hospitalisation; he agreed to follow through on recommendations. He was dismissed after completing a three-week inpatient rehabilitation programme but relapsed to alcohol use three months later, and was readmitted with alcohol withdrawal. He was readmitted two months later (about six months from the first episode) for a second episode of severe alcoholic hepatitis. At admission, his model for end-stage liver disease score was 32 and he was treated again with corticosteroids. His Lille score at seven days was 0.6 and steroids were discontinued. The hospital course was complicated by spontaneous bacterial peritonitis and pneumonia with development of acute kidney injury. He continued to worsen, developing multiorgan failure. After a course of one month, the family’s preference was for him to receive comfort measures. This scenario raises several questions: I. Should liver biopsy have been carried out in this patient before starting treatment for alcoholic hepatitis? II. What should the protocol be for early diagnosis of infection? III. Are there options other than steroid therapy for severe alcoholic hepatitis? Should pharmacological therapy have been initiated to prevent alcohol relapse? IV. What are the determinants of short-term and long-term prognosis in alcoholic hepatitis? V. What is the role of liver transplantation in alcoholic hepatitis?
Published: 2018
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