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1. Faecal proteomics links neutrophil degranulation with mortality in patients with alcohol-associated hepatitis

Author: Kreimeyer, Henriette, Gonzalez, Carlos G, Fondevila, Marcos F, Hsu, Cynthia L, Hartmann, Phillipp, Zhang, Xinlian, Stärkel, Peter, Bosques-Padilla, Francisco, Verna, Elizabeth C, Abraldes, Juan G, Brown, Robert S, Vargas, Victor, Altamirano, Jose, Caballería, Juan, Shawcross, Debbie L, Louvet, Alexandre, Lucey, Michael R, Mathurin, Philippe, Garcia-Tsao, Guadalupe, Bataller, Ramón, Investigators, AlcHepNet, Gonzalez, David J, and Schnabl, Bernd
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Nutrition and Dietetics, Liver Disease, Hepatitis, Clinical Research, Digestive Diseases, Precision Medicine, Substance Misuse, Chronic Liver Disease and Cirrhosis, Alcoholism, Alcohol Use and Health, Biotechnology, Women's Health, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Good Health and Well Being, Humans, Feces, Male, Hepatitis, Alcoholic, Female, Proteomics, Middle Aged, Neutrophils, Biomarkers, Cell Degranulation, Adult, Prognosis, Case-Control Studies, ALCOHOLIC LIVER DISEASE, ALCOHOL-INDUCED INJURY, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology, Clinical sciences, Nutrition and dietetics
Abstract: ObjectivePatients with alcohol-associated hepatitis (AH) have a high mortality. Alcohol exacerbates liver damage by inducing gut dysbiosis, bacterial translocation and inflammation, which is characterised by increased numbers of circulating and hepatic neutrophils.DesignIn this study, we performed tandem mass tag (TMT) proteomics to analyse proteins in the faeces of controls (n=19), patients with alcohol-use disorder (AUD; n=20) and AH (n=80) from a multicentre cohort (InTeam). To identify protein groups that are disproportionately represented, we conducted over-representation analysis using Reactome pathway analysis and Gene Ontology to determine the proteins with the most significant impact. A faecal biomarker and its prognostic effect were validated by ELISA in faecal samples from patients with AH (n=70), who were recruited in a second and independent multicentre cohort (AlcHepNet).ResultFaecal proteomic profiles were overall significantly different between controls, patients with AUD and AH (principal component analysis p=0.001, dissimilarity index calculated by the method of Bray-Curtis). Proteins that showed notable differences across all three groups and displayed a progressive increase in accordance with the severity of alcohol-associated liver disease were predominantly those located in neutrophil granules. Over-representation and Reactome analyses confirmed that differentially regulated proteins are part of granules in neutrophils and the neutrophil degranulation pathway. Myeloperoxidase (MPO), the marker protein of neutrophil granules, correlates with disease severity and predicts 60-day mortality. Using an independent validation cohort, we confirmed that faecal MPO levels can predict short-term survival at 60 days.ConclusionsWe found an increased abundance of faecal proteins linked to neutrophil degranulation in patients with AH, which is predictive of short-term survival and could serve as a prognostic non-invasive marker.
Published: 2025

2. Integrated Multiomics Reveals Glucose Use Reprogramming and Identifies a Novel Hexokinase in Alcoholic Hepatitis

Author: Massey, Veronica, Parrish, Austin, Argemi, Josepmaria, Moreno, Montserrat, Mello, Aline, García-Rocha, Mar, Altamirano, Jose, Odena, Gemma, Dubuquoy, Laurent, Louvet, Alexandre, Martinez, Carlos, Adrover, Anna, Affò, Silvia, Morales-Ibanez, Oriol, Sancho-Bru, Pau, Millán, Cristina, Alvarado-Tapias, Edilmar, Morales-Arraez, Dalia, Caballería, Juan, Mann, Jelena, Cao, Sheng, Sun, Zhaoli, Shah, Vijay, Cameron, Andrew, Mathurin, Phillipe, Snider, Natasha, Villanueva, Càndid, Morgan, Timothy R, Guinovart, Joan, Vadigepalli, Rajanikanth, and Bataller, Ramon
Subjects: Medical Biochemistry and Metabolomics, Biomedical and Clinical Sciences, Clinical Sciences, Liver Disease, Hepatitis, Chronic Liver Disease and Cirrhosis, Alcoholism, Alcohol Use and Health, Substance Misuse, Nutrition, Digestive Diseases, Genetics, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Acute Kidney Injury, Adaptation, Physiological, Animals, Cell Dedifferentiation, Energy Metabolism, Europe, Female, Gene Expression Profiling, Gene Expression Regulation, Enzymologic, Glucose, Glucose-6-Phosphate, Glycogen, Hep G2 Cells, Hepatitis, Alcoholic, Hepatocytes, Hexokinase, Humans, Liver, Male, Metabolome, Metabolomics, Middle Aged, Rats, Wistar, Transcriptome, United States, Alcoholic Liver Disease, Therapeutic Targets, Neurosciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology, Clinical sciences, Nutrition and dietetics
Abstract: Background & aimsWe recently showed that alcoholic hepatitis (AH) is characterized by dedifferentiation of hepatocytes and loss of mature functions. Glucose metabolism is tightly regulated in healthy hepatocytes. We hypothesize that AH may lead to metabolic reprogramming of the liver, including dysregulation of glucose metabolism.MethodsWe performed integrated metabolomic and transcriptomic analyses of liver tissue from patients with AH or alcoholic cirrhosis or normal liver tissue from hepatic resection. Focused analyses of chromatin immunoprecipitation coupled to DNA sequencing was performed. Functional in vitro studies were performed in primary rat and human hepatocytes and HepG2 cells.ResultsPatients with AH exhibited specific changes in the levels of intermediates of glycolysis/gluconeogenesis, the tricarboxylic acid cycle, and monosaccharide and disaccharide metabolism. Integrated analysis of the transcriptome and metabolome showed the used of alternate energetic pathways, metabolite sinks and bottlenecks, and dysregulated glucose storage in patients with AH. Among genes involved in glucose metabolism, hexokinase domain containing 1 (HKDC1) was identified as the most up-regulated kinase in patients with AH. Histone active promoter and enhancer markers were increased in the HKDC1 genomic region. High HKDC1 levels were associated with the development of acute kidney injury and decreased survival. Increased HKDC1 activity contributed to the accumulation of glucose-6-P and glycogen in primary rat hepatocytes.ConclusionsAltered metabolite levels and messenger RNA expression of metabolic enzymes suggest the existence of extensive reprogramming of glucose metabolism in AH. Increased HKDC1 expression may contribute to dysregulated glucose metabolism and represents a novel biomarker and therapeutic target for AH.
Published: 2021

3. Intestinal Virome in Patients With Alcoholic Hepatitis

Author: Jiang, Lu, Lang, Sonja, Duan, Yi, Zhang, Xinlian, Gao, Bei, Chopyk, Jessica, Schwanemann, Leila K, Ventura‐Cots, Meritxell, Bataller, Ramon, Bosques‐Padilla, Francisco, Verna, Elizabeth C, Abraldes, Juan G, Brown, Robert S, Vargas, Victor, Altamirano, Jose, Caballería, Juan, Shawcross, Debbie L, Ho, Samuel B, Louvet, Alexandre, Lucey, Michael R, Mathurin, Philippe, Garcia‐Tsao, Guadalupe, Kisseleva, Tatiana, Brenner, David A, Tu, Xin M, Stärkel, Peter, Pride, David, Fouts, Derrick E, and Schnabl, Bernd
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Hepatitis, Substance Misuse, Alcoholism, Alcohol Use and Health, Chronic Liver Disease and Cirrhosis, Women's Health, Health Disparities, Digestive Diseases, Microbiome, Infectious Diseases, Clinical Research, Liver Disease, Oral and gastrointestinal, Infection, Good Health and Well Being, Adult, Aged, Animals, Bacteriophages, Case-Control Studies, DNA, Viral, End Stage Liver Disease, Feces, Female, Hepatitis, Alcoholic, Herpesviridae, Humans, Intestinal Mucosa, Liver, Liver Cirrhosis, Male, Metagenomics, Middle Aged, Parvoviridae, RNA, Viral, Severity of Illness Index, Survival Rate, Virome, Medical Biochemistry and Metabolomics, Immunology, Gastroenterology & Hepatology, Clinical sciences
Abstract: Background and aimsAlcoholic hepatitis (AH) is a severe manifestation of alcohol-associated liver disease (ALD) with high mortality. Although gut bacteria and fungi modulate disease severity, little is known about the effects of the viral microbiome (virome) in patients with ALD.Approach and resultsWe extracted virus-like particles from 89 patients with AH who were enrolled in a multicenter observational study, 36 with alcohol use disorder (AUD), and 17 persons without AUD (controls). Virus-like particles from fecal samples were fractionated using differential filtration techniques, and metagenomic sequencing was performed to characterize intestinal viromes. We observed an increased viral diversity in fecal samples from patients with ALD, with the most significant changes in samples from patients with AH. Escherichia-, Enterobacteria-, and Enterococcus phages were over-represented in fecal samples from patients with AH, along with significant increases in mammalian viruses such as Parvoviridae and Herpesviridae. Antibiotic treatment was associated with higher viral diversity. Specific viral taxa, such as Staphylococcus phages and Herpesviridae, were associated with increased disease severity, indicated by a higher median Model for End-Stage Liver Disease score, and associated with increased 90-day mortality.ConclusionsIn conclusion, intestinal viral taxa are altered in fecal samples from patients with AH and associated with disease severity and mortality. Our study describes an intestinal virome signature associated with AH.
Published: 2020

4. Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease.

Author: Duan, Yi, Llorente, Cristina, Lang, Sonja, Brandl, Katharina, Chu, Huikuan, Jiang, Lu, White, Richard C, Clarke, Thomas H, Nguyen, Kevin, Torralba, Manolito, Shao, Yan, Liu, Jinyuan, Hernandez-Morales, Adriana, Lessor, Lauren, Rahman, Imran R, Miyamoto, Yukiko, Ly, Melissa, Gao, Bei, Sun, Weizhong, Kiesel, Roman, Hutmacher, Felix, Lee, Suhan, Ventura-Cots, Meritxell, Bosques-Padilla, Francisco, Verna, Elizabeth C, Abraldes, Juan G, Brown, Robert S, Vargas, Victor, Altamirano, Jose, Caballería, Juan, Shawcross, Debbie L, Ho, Samuel B, Louvet, Alexandre, Lucey, Michael R, Mathurin, Philippe, Garcia-Tsao, Guadalupe, Bataller, Ramon, Tu, Xin M, Eckmann, Lars, van der Donk, Wilfred A, Young, Ry, Lawley, Trevor D, Stärkel, Peter, Pride, David, Fouts, Derrick E, and Schnabl, Bernd
Subjects: Liver, Hepatocytes, Feces, Animals, Mice, Inbred C57BL, Humans, Mice, Enterococcus faecalis, Bacteriophages, Fatty Liver, Hepatitis, Alcoholic, Alcoholism, Ethanol, Germ-Free Life, Female, Male, Perforin, Gastrointestinal Microbiome, Phage Therapy, Alcoholism, Alcohol Use and Health, Clinical Research, Liver Disease, Substance Abuse, Chronic Liver Disease and Cirrhosis, Hepatitis, Infectious Diseases, Digestive Diseases, 2.1 Biological and endogenous factors, Oral and gastrointestinal, General Science & Technology
Abstract: Chronic liver disease due to alcohol-use disorder contributes markedly to the global burden of disease and mortality1-3. Alcoholic hepatitis is a severe and life-threatening form of alcohol-associated liver disease. The gut microbiota promotes ethanol-induced liver disease in mice4, but little is known about the microbial factors that are responsible for this process. Here we identify cytolysin-a two-subunit exotoxin that is secreted by Enterococcus faecalis5,6-as a cause of hepatocyte death and liver injury. Compared with non-alcoholic individuals or patients with alcohol-use disorder, patients with alcoholic hepatitis have increased faecal numbers of E. faecalis. The presence of cytolysin-positive (cytolytic) E. faecalis correlated with the severity of liver disease and with mortality in patients with alcoholic hepatitis. Using humanized mice that were colonized with bacteria from the faeces of patients with alcoholic hepatitis, we investigated the therapeutic effects of bacteriophages that target cytolytic E. faecalis. We found that these bacteriophages decrease cytolysin in the liver and abolish ethanol-induced liver disease in humanized mice. Our findings link cytolytic E. faecalis with more severe clinical outcomes and increased mortality in patients with alcoholic hepatitis. We show that bacteriophages can specifically target cytolytic E. faecalis, which provides a method for precisely editing the intestinal microbiota. A clinical trial with a larger cohort is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with alcoholic hepatitis.
Published: 2019

5. Dysregulation of serum bile acids and FGF19 in alcoholic hepatitis

Author: Brandl, Katharina, Hartmann, Phillipp, Jih, Lily J, Pizzo, Donald P, Argemi, Josepmaria, Ventura-Cots, Meritxell, Coulter, Sally, Liddle, Christopher, Ling, Lei, Rossi, Stephen J, DePaoli, Alex M, Loomba, Rohit, Mehal, Wajahat Z, Fouts, Derrick E, Lucey, Michael R, Bosques-Padilla, Francisco, Mathurin, Philippe, Louvet, Alexander, Garcia-Tsao, Guadalupe, Verna, Elizabeth C, Abraldes, Juan G, Brown, Robert S, Vargas, Victor, Altamirano, Jose, Caballería, Juan, Shawcross, Debbie, Stärkel, Peter, Ho, Samuel B, Bataller, Ramon, and Schnabl, Bernd
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Substance Misuse, Genetics, Chronic Liver Disease and Cirrhosis, Liver Disease, Hepatitis, Digestive Diseases, Alcoholism, Alcohol Use and Health, 2.1 Biological and endogenous factors, Aetiology, Oral and gastrointestinal, Good Health and Well Being, Bile Acids and Salts, Biomarkers, Cholestasis, Correlation of Data, Female, Fibroblast Growth Factors, Hepatitis, Alcoholic, Humans, Male, Middle Aged, Neutrophil Infiltration, Neutrophils, Severity of Illness Index, Signal Transduction, FGF19, Bile acids, Microbiome, Public Health and Health Services, Gastroenterology & Hepatology, Clinical sciences
Abstract: Background & aimsThe degree of cholestasis is an important disease driver in alcoholic hepatitis, a severe clinical condition that needs new biomarkers and targeted therapies. We aimed to identify the largely unknown mechanisms and biomarkers linked to cholestasis in alcoholic hepatitis.MethodsHerein, we analyzed a well characterized cohort of patients with alcoholic hepatitis and correlated clinical and histological parameters and outcomes with serum bile acids and fibroblast growth factor 19 (FGF19), a major regulator of bile acid synthesis.ResultsWe found that total and conjugated bile acids were significantly increased in patients with alcoholic hepatitis compared with controls. Serum FGF19 levels were strongly increased and gene expression of FGF19 was induced in biliary epithelial cells and ductular cells of patients with alcoholic hepatitis. De novo bile acid synthesis (CYP7A1 gene expression and C4 serum levels) was significantly decreased in patients with alcoholic hepatitis. Importantly, total and conjugated bile acids correlated positively with FGF19 and with disease severity (model for end-stage liver disease score). FGF19 correlated best with conjugated cholic acid, and model for end-stage liver disease score best with taurine-conjugated chenodeoxycholic acid. Univariate analysis demonstrated significant associations between FGF19 and bilirubin as well as gamma glutamyl transferase, and negative correlations between FGF19 and fibrosis stage as well as polymorphonuclear leukocyte infiltration, in all patients with alcoholic hepatitis.ConclusionSerum FGF19 and bile acids are significantly increased in patients with alcoholic hepatitis, while de novo bile acid synthesis is suppressed. Modulation of bile acid metabolism or signaling could represent a promising target for treatment of alcoholic hepatitis in humans.Lay summaryUnderstanding the underlying mechanisms that drive alcoholic hepatitis is important for the development of new biomarkers and targeted therapies. Herein, we describe a molecule that is increased in patients with alcoholic hepatitis. Modulating the molecular pathway of this molecule might lead to promising targets for the treatment of alcoholic hepatitis.
Published: 2018

6. Evaluation of laboratory tests for cirrhosis and for alcohol use, in the context of alcoholic cirrhosis.

Author: Whitfield, John, Masson, Steven, Liangpunsakul, Suthat, Hyman, Jessica, Mueller, Sebastian, Aithal, Guruprasad, Eyer, Florian, Gleeson, Dermot, Thompson, Andrew, Stickel, Felix, Soyka, Michael, Daly, Ann, Cordell, Heather, Liang, Tiebing, Foroud, Tatiana, Lumeng, Lawrence, Pirmohamed, Munir, Nalpas, Bertrand, Bence, Camille, Jacquet, Jean-Marc, Louvet, Alexandre, Moirand, Romain, Nahon, Pierre, Naveau, Sylvie, Perney, Pascal, Podevin, Philippe, Haber, Paul, Seitz, Helmut, Day, Christopher, Mathurin, Philippe, Morgan, Timothy, and Seth, Devanshi
Subjects: Abstinence, Alcohol, Aspartate aminotransferase, Cirrhosis, Gamma glutamyl transferase, Adult, Alcohol Abstinence, Alcohol Drinking, Area Under Curve, Aspartate Aminotransferases, Bilirubin, Biomarkers, Case-Control Studies, Clinical Enzyme Tests, Europe, Female, Humans, International Normalized Ratio, Liver Cirrhosis, Alcoholic, Liver Function Tests, Male, Middle Aged, Predictive Value of Tests, ROC Curve, Reproducibility of Results, Risk Factors, Sex Factors, United States, gamma-Glutamyltransferase
Abstract: Laboratory tests can play an important role in assessment of alcoholic patients, including for evaluation of liver damage and as markers of alcohol intake. Evidence on test performance should lead to better selection of appropriate tests and improved interpretation of results. We compared laboratory test results from 1578 patients between cases (with alcoholic cirrhosis; 753 men, 243 women) and controls (with equivalent lifetime alcohol intake but no liver disease; 439 men, 143 women). Comparisons were also made between 631 cases who had reportedly been abstinent from alcohol for over 60 days and 364 who had not. ROC curve analysis was used to estimate and compare tests ability to distinguish patients with and without cirrhosis, and abstinent and drinking cases. The best tests for presence of cirrhosis were INR and bilirubin, with areas under the ROC curve (AUCs) of 0.91 ± 0.01 and 0.88 ± 0.01, respectively. Confining analysis to patients with no current or previous ascites gave AUCs of 0.88 ± 0.01 for INR and 0.85 ± 0.01 for bilirubin. GGT and AST showed discrimination between abstinence and recent drinking in patients with cirrhosis, including those without ascites, when appropriate (and for GGT, sex-specific) limits were used. For AST, a cut-off limit of 85 units/L gave 90% specificity and 37% sensitivity. For GGT, cut-off limits of 288 units/L in men and 138 units/L in women gave 90% specificity for both and 40% sensitivity in men, 63% sensitivity in women. INR and bilirubin show the best separation between patients with alcoholic cirrhosis (with or without ascites) and control patients with similar lifetime alcohol exposure. Although AST and GGT are substantially increased by liver disease, they can give useful information on recent alcohol intake in patients with alcoholic cirrhosis when appropriate cut-off limits are used.
Published: 2018

7. Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo

Author: Yadav, Mahesh, Louvet, Cedric, Davini, Dan, Gardner, James M, Martinez-Llordella, Marc, Bailey-Bucktrout, Samantha, Anthony, Bryan A, Sverdrup, Francis M, Head, Richard, Kuster, Daniel J, Ruminski, Peter, Weiss, David, Von Schack, David, and Bluestone, Jeffrey A
Subjects: Biomedical and Clinical Sciences, Immunology, Autoimmune Disease, Underpinning research, 1.1 Normal biological development and functioning, Inflammatory and immune system, Animals, Autoimmunity, Gene Expression Regulation, Lymphocyte Activation, Lymphoid Tissue, Male, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, Transgenic, Myelin Basic Protein, Neuropilin-1, Receptors, Antigen, T-Cell, T-Lymphocyte Subsets, T-Lymphocytes, Regulatory, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract: Foxp3(+) CD4(+) T helper cells called regulatory T (T reg) cells play a key role in controlling reactivity to self-antigens and onset of autoimmunity. T reg cells either arise in thymus and are called natural T reg (nT reg) cells or are generated in the periphery through induction of Foxp3 and are called inducible T reg (iT reg) cells. The relative contributions of iT reg cells and nT reg cells in peripheral tolerance remain unclear as a result of an inability to separate these two subsets of T reg cells. Using a combination of novel TCR transgenic mice with a defined self-antigen specificity and conventional mouse models, we demonstrate that a cell surface molecule, neuropilin-1 (Nrp-1), is expressed at high levels on nT reg cells and can be used to separate nT reg versus iT reg cells in certain physiological settings. In addition, iT reg cells generated through antigen delivery or converted under homeostatic conditions lack Nrp-1 expression. Nrp-1(lo) iT reg cells show similar suppressive activity to nT reg cells in controlling ongoing autoimmune responses under homeostatic conditions. In contrast, their activity might be compromised in certain lymphopenic settings. Collectively, our data show that Nrp-1 provides an excellent marker to distinguish distinct T reg subsets and will be useful in studying the role of nT reg versus iT reg cells in different disease settings.
Published: 2012

8. Lung Infection Affects Access to Treatment and Short-Term Outcome in Patients With Severe Alcohol-Related Hepatitis Treated With Corticosteroids

Author: Line Carolle Ntandja Wandji, Massih Ningarhari, Elise Lemaître, Marion Khaldi, Pierre Saffers, Julien Lollivier, Guillaume Lassailly, Sébastien Dharancy, Philippe Mathurin, and Alexandre Louvet
Subjects: Male, Brain Diseases, Hepatology, Hepatitis, Alcoholic, Gastroenterology, Pneumonia, Middle Aged, Prognosis, Severity of Illness Index, Health Services Accessibility, End Stage Liver Disease, Adrenal Cortex Hormones, Humans, Female, Lung
Abstract: Severe alcohol-related hepatitis (AH) is associated with an increased risk of infection, but the impact of pneumonia has not been specifically analyzed in a specific cohort.All patients admitted for severe AH between 2002 and 2020 were prospectively included. Systematic screening for infection was performed at admission and renewed in the case of clinical suspicion.We included 614 patients (60.4% men, mean age 49.9 years, median model for end-stage liver disease [MELD] 25.2, bilirubin 18.1 mg/dL), 202 (32.9%) with infections at admission (73 lung infections). Encephalopathy ( P = 0.006), MELD score ( P = 0.0002), and tobacco exposure (past vs never smokers: P = 0.002 or active vs past smokers: P = 0.005) were associated with lung infection at admission on multivariate analysis. Factors independently associated with death before steroid initiation were encephalopathy ( P = 0.003), MELD score ( P = 0.05), and especially lung infection ( P0.0001). Thus, patients with a lung infection had a lower probability of receiving steroids than those with other infections and noninfected patients: 54.8 vs 88.4 vs 98.1% ( P0.0001). One hundred forty-six of the 558 patients who received corticosteroids developed infection, including 57 (39.04%) pneumonias. The risk of respiratory and nonrespiratory infection was higher in nonresponders to steroids (Lille score ≥0.45) than in responders: 13% vs 7.6%, P = 0.03 and 27.9% vs 10.6%, P0.001, respectively. The variables independently associated with 3-month mortality after steroid initiation were lung infection ( P = 0.004), nonresponse to steroids ( P0.0001), MELD score ( P = 0.0003), ascites ( P = 0.003), and encephalopathy ( P = 0.018), whereas nonrespiratory infections were not ( P = 0.91).Lung infection is frequent during severe AH and influences mortality at admission and after steroid initiation. These results emphasize the need for specific management of lung infection during the course of AH.
Published: 2022
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9. Hyperprogressive Disease After Pembrolizumab Treatment in Advanced Epstein-Barr Virus–Associated Gastric Adenocarcinoma With ERBB2 Amplification

Author: Sarah Watson, Julien Masliah Planchon, Joanna Cyrta, Pauline Vaflard, Ivan Bièche, François-Clément Bidard, Marine Lefevre, Christophe Louvet, Vincent Servois, and Emilie Soularue
Subjects: Male, Epstein-Barr Virus Infections, Cancer Research, Receptor, ErbB-2, business.industry, Pembrolizumab, Disease, Adenocarcinoma, Antibodies, Monoclonal, Humanized, medicine.disease_cause, Epstein–Barr virus, Gastric adenocarcinoma, ERBB2 Amplification, Oncology, Stomach Neoplasms, Positron Emission Tomography Computed Tomography, Cancer research, Humans, Medicine, Tomography, X-Ray Computed, business, Immune Checkpoint Inhibitors, Aged
Published: 2021
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10. 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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11. 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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12. The MELD Score Is Superior to the Maddrey Discriminant Function Score to Predict Short-Term Mortality in Alcohol-Associated Hepatitis: A Global Study

Author: D. Morales-Arráez, M. Ventura-Cots, J. Altamirano, J.G. Abraldes, M. Cruz-Lemini, M.R. Thursz, S.R. Atkinson, S.K. Sarin, W. Kim, R. Chavez-Araujo, M.F. Higuera-de la Tijera, A.K. Singal, V.H. Shah, P.S. Kamath, A. Duarte-Rojo, E.A. Charles, V. Vargas, M. Jager, P.E. Rautou, D. Rincon, F. Zamarripa, J.C. Restrepo-Gutiérrez, A. Torre, M.R. Lucey, J.P. Arab, P. Mathurin, A. Louvet, G. García-Tsao, J.A. González, E.C. Verna, R.S. Brown, J. Argemi, C. Fernández-Carillo, A. Clemente, E. Alvarado-Tapias, E. Forrest, M. Allison, and R. Bataller
Subjects: survival rate, Adult, Male, Time Factors, global health, complication, Global Health, liver, Severity of Illness Index, Article, End Stage Liver Disease, Liver Function Tests, Risk Factors, time factor, middle aged, follow up, Humans, liver function test, human, pathophysiology, receiver operating characteristic, Hepatology, Hepatitis, Alcoholic, Gastroenterology, Discriminant Analysis, clinical trial, Middle Aged, Prognosis, mortality, Survival Rate, female, multicenter study, Liver, risk factor, ROC Curve, Female, alcohol liver disease, Follow-Up Studies
Abstract: INTRODUCTION:Several scoring systems predict mortality in alcohol-associated hepatitis (AH), including the Maddrey discriminant function (mDF) and model for end-stage liver disease (MELD) score developed in the United States, Glasgow alcoholic hepatitis score in the United Kingdom, and age, bilirubin, international normalized ratio, and creatinine score in Spain. To date, no global studies have examined the utility of these scores, nor has the MELD-sodium been evaluated for outcome prediction in AH. In this study, we assessed the accuracy of different scores to predict short-term mortality in AH and investigated additional factors to improve mortality prediction.METHODS:Patients admitted to hospital with a definite or probable AH were recruited by 85 tertiary centers in 11 countries and across 3 continents. Baseline demographic and laboratory variables were obtained. The primary outcome was all-cause mortality at 28 and 90 days.RESULTS:In total, 3,101 patients were eligible for inclusion. After exclusions (n = 520), 2,581 patients were enrolled (74.4% male, median age 48 years, interquartile range 40.9-55.0 years). The median MELD score was 23.5 (interquartile range 20.5-27.8). Mortality at 28 and 90 days was 20% and 30.9%, respectively. The area under the receiver operating characteristic curve for 28-day mortality ranged from 0.776 for MELD-sodium to 0.701 for mDF, and for 90-day mortality, it ranged from 0.773 for MELD to 0.709 for mDF. The area under the receiver operating characteristic curve for mDF to predict death was significantly lower than all other scores. Age added to MELD obtained only a small improvement of AUC.DISCUSSION:These results suggest that the mDF score should no longer be used to assess AH's prognosis. The MELD score has the best performance in predicting short-term mortality. © 2021 by The American College of Gastroenterology.
Published: 2022

13. 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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14. 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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15. 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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16. 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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17. Pupillary Pain Index Changes After a Standardized Bolus of Alfentanil Under Sevoflurane Anesthesia

Author: Nada Sabourdin, Coumba Diarra, Nicolas Louvet, Isabelle Constant, Véronique Piat, and Risa Wolk
Subjects: Male, Schmidt sting pain index, Adolescent, Pilot Projects, Anesthesia, General, Sevoflurane, 03 medical and health sciences, 0302 clinical medicine, Bolus (medicine), 030202 anesthesiology, medicine, Pupillary response, Humans, Prospective Studies, Alfentanil, Child, Pain Measurement, business.industry, Pupil, Analgesics, Opioid, Anesthesiology and Pain Medicine, Child, Preschool, Anesthesia, Anesthetics, Inhalation, Injections, Intravenous, Female, Analgesia, business, 030217 neurology & neurosurgery, medicine.drug, Sevoflurane anesthesia
Abstract: The pupillary pain index (PPI) is a novel pupillometric index, designed to assess intraoperative analgesia. It is based on the evaluation of the pupillary response to electrical stimuli of increasing intensity. It ranges from 1 (low level of pupillary reactivity, high level of analgesia) to 10 (high level of pupillary reactivity, low level of analgesia). In this first evaluation of the PPI, our objective was to investigate the PPI changes after a bolus of 10 µg·kg(-1) of alfentanil in children under sevoflurane general anesthesia.After ethics committee approval and informed consent, 20 healthy children (9 ± 5 years) undergoing elective surgery under general anesthesia were included in this prospective, open, registered pilot study (NCT02646592). Anesthetic induction was standardized with sevoflurane 6% and propofol 1 mg·kg(-1). After tracheal intubation, sevoflurane concentration was maintained at 2% for 10 minutes. A first PPI measurement was performed (PPI-1), and a bolus of 10 µg·kg(-1) was administered. Two minutes after this bolus, a second PPI measurement was performed (PPI-2). Heart rate, blood pressure, and bispectral index were recorded before and after each PPI measurement. Resting pupillary diameter was recorded before each PPI measurement. PPI scores before and after the bolus of alfentanil were compared using a Wilcoxon signed rank test.PPI scores decreased after administration of a bolus of alfentanil (median difference: -3 [95% confidence interval, -4 to -2]). The median (quartiles) of PPI-1 (baseline, before alfentanil) was 6 (4, 7), and the median (quartiles) of PPI-2 (after alfentanil) was 2 (2, 3) (P.001). No difference was found in resting pupillary diameter before PPI-1 and PPI-2 (2.2 ± 0.2 and 2.2 ± 0.3 mm, respectively; P = .86). There were no significant changes in heart rate or blood pressure after PPI measurements (P = .46 and .49, respectively). Bispectral index was slightly increased after PPI measurements (P = .01; mean bispectral index increase5%). No withdrawal movements occurred during PPI measurements.There was a significant decrease in PPI after alfentanil administration. The results of this pilot study suggest that PPI score decreases when the level of analgesia increases. PPI measurement was not associated with a clinical or hemodynamic nociceptive response. This new index might provide useful information to individually adapt opioid administration before nociceptive stimuli under general anesthesia.
Published: 2019
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18. Dendritic Cells Require TMEM176A/B Ion Channels for Optimal MHC Class II Antigen Presentation to Naive CD4 + T Cells

Author: Saeed Abdu Rahiman, Melanie Lancien, Amandine Even, Séverine Remy, Maria-Cristina Cuturi, Veronica De Simone, Lucile Gueno, Elise Chiffoleau, Sonia Salle, Aurélie Moreau, Geraldine Bienvenu, Steven M. Kerfoot, Alice Molle, Gaelle Beriou, Flora Coulon, Régis Josien, Magalie Feyeux, Franck Perez, Susan Chan, Cynthia Fourgeux, Emmanuel Merieau, Gianluca Matteoli, Peggy Kirstetter, Laurence Bouchet-Delbos, Jeremie Poschmann, Cédric Louvet, Gaelle Boncompain, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), Structure fédérative de recherche François Bonamy (SFR François Bonamy), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN), University of Western Ontario (UWO), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Biologie Cellulaire et Cancer, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Boncompain, Gaelle
Subjects: CD4-Positive T-Lymphocytes, Male, [SDV.IMM] Life Sciences [q-bio]/Immunology, T cell, [SDV]Life Sciences [q-bio], Genes, MHC Class II, Immunology, Golgi Apparatus, Priming (immunology), Tretinoin, Endosomes, Ion Channels, MHC class II antigen, Mice, 03 medical and health sciences, 0302 clinical medicine, Intestinal mucosa, medicine, Animals, Immunology and Allergy, Lymphocytes, Intestinal Mucosa, Ion channel, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Mice, Knockout, Orphan receptor, Antigen Presentation, 0303 health sciences, MHC class II, biology, Chemistry, Innate lymphoid cell, Histocompatibility Antigens Class II, Membrane Proteins, Dendritic Cells, Immunity, Innate, Cell biology, Mice, Inbred C57BL, medicine.anatomical_structure, 030220 oncology & carcinogenesis, biology.protein, Th17 Cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Lysosomes
Abstract: Intracellular ion fluxes emerge as critical actors of immunoregulation but still remain poorly explored. In this study, we investigated the role of the redundant cation channels TMEM176A and TMEM176B (TMEM176A/B) in retinoic acid–related orphan receptor γt+ cells and conventional dendritic cells (DCs) using germline and conditional double knockout mice. Although Tmem176a/b appeared surprisingly dispensable for the protective function of Th17 and group 3 innate lymphoid cells in the intestinal mucosa, we found that they were required in conventional DCs for optimal Ag processing and presentation to CD4+ T cells. Using a real-time imaging method, we show that TMEM176A/B accumulate in dynamic post-Golgi vesicles preferentially linked to the late endolysosomal system and strongly colocalize with HLA-DM. Taken together, our results suggest that TMEM176A/B ion channels play a direct role in the MHC class II compartment of DCs for the fine regulation of Ag presentation and naive CD4+ T cell priming.
Published: 2021
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19. 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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20. 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

21. Prognostic Value and Relation with Adjuvant Treatment Duration of ctDNA in Stage III Colon Cancer: a

Author: Julien, Taieb, Valérie, Taly, Julie, Henriques, Camille, Bourreau, Laurent, Mineur, Jaafar, Bennouna, Jérôme, Desrame, Christophe, Louvet, Céline, Lepere, May, Mabro, Joëlle, Egreteau, Olivier, Bouche, Claire, Mulot, Katia, Hormigos, Kariman, Chaba, Thibault, Mazard, Aimery, de Gramont, Dewi, Vernerey, Thierry, André, and Pierre, Laurent-Puig
Subjects: Male, Duration of Therapy, Chemotherapy, Adjuvant, Colonic Neoplasms, Humans, Female, Prospective Studies, Prognosis, Disease-Free Survival, Article, Aged, Circulating Tumor DNA, Neoplasm Staging
Abstract: 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.ctDNA was tested forOf 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 (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.
Published: 2021

22. Integrated Multiomics Reveals Glucose Use Reprogramming and Identifies a Novel Hexokinase in Alcoholic Hepatitis

Author: Natasha T. Snider, Jelena Mann, Alexandre Louvet, Veronica Massey, Rajanikanth Vadigepalli, Pau Sancho-Bru, José Altamirano, Sheng Cao, Vijay H. Shah, Joan J. Guinovart, Juan Caballería, Càndid Villanueva, Zhaoli Sun, Aline Mello, Oriol Morales-Ibanez, Dalia Morales-Arraez, Carlos Prieto Martinez, Anna Adrover, Gemma Odena, Silvia Affò, Montserrat Moreno, Edilmar Alvarado-Tapias, Laurent Dubuquoy, Ramon Bataller, Andrew M. Cameron, Austin Parrish, Mar García-Rocha, Cristina Millán, P. Mathurin, Timothy R. Morgan, and Josepmaria Argemi
Subjects: 0301 basic medicine, Enzymologic, Male, Alcoholic liver disease, Alcoholic Liver Disease, Metabolite, Wistar, Hepatitis, chemistry.chemical_compound, Alcohol Use and Health, Substance Misuse, 0302 clinical medicine, Hexokinase, 2.1 Biological and endogenous factors, Glycolysis, Aetiology, Glycogen, Liver Disease, Gastroenterology, Hep G2 Cells, Middle Aged, Acute Kidney Injury, Alcoholic, HKDC1, Adaptation, Physiological, Europe, Alcoholism, Biochemistry, Liver, Metabolome, 030211 gastroenterology & hepatology, Female, Physiological, Chronic Liver Disease and Cirrhosis, Clinical Sciences, Glucose-6-Phosphate, Carbohydrate metabolism, Article, Gene Expression Regulation, Enzymologic, Paediatrics and Reproductive Medicine, 03 medical and health sciences, medicine, Genetics, Animals, Humans, Metabolomics, Rats, Wistar, Adaptation, Nutrition, Hepatology, Gastroenterology & Hepatology, Hepatitis, Alcoholic, Gene Expression Profiling, Neurosciences, Cell Dedifferentiation, medicine.disease, United States, Rats, 030104 developmental biology, Glucose, Good Health and Well Being, chemistry, Glucose 6-phosphate, Gene Expression Regulation, Hepatocytes, Energy Metabolism, Transcriptome, Digestive Diseases, Therapeutic Targets
Abstract: Background & Aims We recently showed that alcoholic hepatitis (AH) is characterized by dedifferentiation of hepatocytes and loss of mature functions. Glucose metabolism is tightly regulated in healthy hepatocytes. We hypothesize that AH may lead to metabolic reprogramming of the liver, including dysregulation of glucose metabolism. Methods We performed integrated metabolomic and transcriptomic analyses of liver tissue from patients with AH or alcoholic cirrhosis or normal liver tissue from hepatic resection. Focused analyses of chromatin immunoprecipitation coupled to DNA sequencing was performed. Functional in vitro studies were performed in primary rat and human hepatocytes and HepG2 cells. Results Patients with AH exhibited specific changes in the levels of intermediates of glycolysis/gluconeogenesis, the tricarboxylic acid cycle, and monosaccharide and disaccharide metabolism. Integrated analysis of the transcriptome and metabolome showed the used of alternate energetic pathways, metabolite sinks and bottlenecks, and dysregulated glucose storage in patients with AH. Among genes involved in glucose metabolism, hexokinase domain containing 1 (HKDC1) was identified as the most up-regulated kinase in patients with AH. Histone active promoter and enhancer markers were increased in the HKDC1 genomic region. High HKDC1 levels were associated with the development of acute kidney injury and decreased survival. Increased HKDC1 activity contributed to the accumulation of glucose-6-P and glycogen in primary rat hepatocytes. Conclusions Altered metabolite levels and messenger RNA expression of metabolic enzymes suggest the existence of extensive reprogramming of glucose metabolism in AH. Increased HKDC1 expression may contribute to dysregulated glucose metabolism and represents a novel biomarker and therapeutic target for AH.
Published: 2021

23. 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

24. 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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25. 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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26. 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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27. 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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28. 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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29. Regulatory T Cells Expressing Tumor Necrosis Factor Receptor Type 2 Play a Major Role in CD4+ T-Cell Impairment During Sepsis

Author: Tanguy Chaumette, Jeremie Poschmann, Fanny Coulpier, Sophie Lemoine, Antoine Asquier, Jocelyne Caillon, Emilie Ronin, Benoît L. Salomon, Benjamin Gaborit, Virginie Le Mabecque, David Boutoille, Marie Chauveau, Cédric Jacqueline, Mickael Vourc'h, Alexandre Bourdiol, Karim Asehnoune, Antoine Roquilly, Benoit Tessoulin, Abderrahmane Sadek, Marion Davieau, Alexis Broquet, Cédric Louvet, Thérapeutiques cliniques et expérimentales des infections (EA 3826) (EA 3826), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Hôpital Hôtel-Dieu de Nantes - Centre Hospitalier Universitaire de Nantes (Hôpital Hôtel-Dieu de Nantes - CHU de Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique, Institut de Biologie de l’Ecole Normale Superieure, Paris, France
Subjects: CD4-Positive T-Lymphocytes, Male, 0301 basic medicine, Staphylococcus aureus, Secondary infection, medicine.medical_treatment, [SDV]Life Sciences [q-bio], chemical and pharmacologic phenomena, medicine.disease_cause, T-Lymphocytes, Regulatory, Sepsis, Mice, 03 medical and health sciences, 0302 clinical medicine, In vivo, medicine, Animals, Humans, Receptors, Tumor Necrosis Factor, Type II, Immunology and Allergy, Cells, Cultured, Immunosuppression Therapy, Mice, Knockout, Effector, business.industry, Immunosuppression, hemic and immune systems, medicine.disease, In vitro, 3. Good health, Mice, Inbred C57BL, 030104 developmental biology, Infectious Diseases, 030220 oncology & carcinogenesis, CD4 Antigens, Immunology, Female, Tumor necrosis factor receptor 2, business
Abstract: Sepsis causes inflammation-induced immunosuppression with lymphopenia and alterations of CD4+ T-cell functions that renders the host prone to secondary infections. Whether and how regulatory T cells (Treg) are involved in this postseptic immunosuppression is unknown. We observed in vivo that early activation of Treg during Staphylococcus aureus sepsis induces CD4+ T-cell impairment and increases susceptibility to secondary pneumonia. The tumor necrosis factor receptor 2 positive (TNFR2pos) Treg subset endorsed the majority of effector immunosuppressive functions, and TNRF2 was particularly associated with activation of genes involved in cell cycle and replication in Treg, probably explaining their maintenance. Blocking or deleting TNFR2 during sepsis decreased the susceptibility to secondary infection. In humans, our data paralleled those in mice; the expression of CTLA-4 was dramatically increased in TNFR2pos Treg after culture in vitro with S. aureus. Our findings describe in vivo mechanisms underlying sepsis-induced immunosuppression and identify TNFR2pos Treg as targets for therapeutic intervention.
Published: 2020
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30. 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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31. 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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32. 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

33. 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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34. 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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35. Consequences of TIPSS placement on the body composition of patients with cirrhosis and severe portal hypertension: a large retrospective CT-based surveillance

Author: Florent, Artru, Xavier, Miquet, Mustapha, Azahaf, Julien, Labreuche, Line Carolle, Ntandja Wandji, Géraldine, Sergent, Amélie, Nobécourt, Pierre, Toumelin, Guillaume, Lassailly, Sébastien, Dharancy, Olivier, Ernst, Philippe, Mathurin, and Alexandre, Louvet
Subjects: Liver Cirrhosis, Male, Sarcopenia, Hypertension, Portal, Body Composition, Humans, Female, Middle Aged, Portasystemic Shunt, Transjugular Intrahepatic, Tomography, X-Ray Computed, Retrospective Studies
Abstract: Body composition may be modified after improvement of portal hypertension (PHT) by transjugular intrahepatic portosystemic shunt (TIPSS) insertion.To evaluate changes in body composition following TIPSS placement, their relationship with radiological TIPSS patency and function, and the predictive value of these parameters METHODS: We retrospectively included 179 patients with cirrhosis who underwent TIPSS placement in our centre for severe PHT from 2011 to 2017. CT scan-based surveillance was performed at baseline, 1-3 (M1-M3) and 6 months (M6).The median model for end-stage liver disease (MELD) score was 11.4 (8.8-15.1) and Child-Pugh score 8 (7-9). Only the MELD score (HR 1.14, 95% CI 1.08-1.20) and sarcopenia assessed by transversal right psoas muscle thickness at the umbilical level/height (TPMPT/height) (HR 0.86, 95% CI 0.79-0.96) were independently associated with 6-month mortality on multivariate analysis. After TIPSS insertion, TPMT/height increased from 19 mm/m (baseline) to 19.6 mm/m (M1-M3, P = 0.004) and 21.1 mm/m (M6, P0.0001). The improvement and its extent were dependent on the radiological patency and dysfunction of TIPSS. Subcutaneous fat surface (SCFS) increased from 183.4 to 193 cmSarcopenia is independently associated with 6-month outcome and improves after TIPSS placement, together with an inverse evolution of subcutaneous and visceral fat. TIPSS not only treats PHT but also improves body composition.
Published: 2020

36. Recurrence patterns after laparoscopic resection of colorectal liver metastases

Author: Brice Gayet, Gianfranco Donatelli, Nicolas Tabchouri, Mostefa Bennamoun, Christophe Louvet, Shinya Okumura, Marc Beaussier, and David Fuks
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, 030230 surgery, Gastroenterology, Resection, Metastasis, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Hepatectomy, Humans, Laparoscopic resection, Aged, Retrospective Studies, Chemotherapy, business.industry, Liver Neoplasms, Middle Aged, Hepatology, Prognosis, medicine.disease, Primary tumor, Outcome and Process Assessment, Health Care, 030220 oncology & carcinogenesis, Female, Laparoscopy, Surgery, France, Neoplasm Recurrence, Local, Colorectal Neoplasms, business, Abdominal surgery
Abstract: The major issue after liver resection for colorectal liver metastases (CRLM) is the high incidence of recurrence. Unlike open liver resection (OLR), recurrence following laparoscopic liver resection (LLR) is not well documented. The aim of this study was to analyze recurrence patterns and treatment following LLR for CRLM. All patients who underwent LLR for CRLM from 2000 to 2016 were reviewed. Patients who presented with recurrence were compared to those who did not. Recurrence-free survival (RFS), overall survival (OS), and risk of recurrence and survival prognostic factors were analyzed. Overall, 273 patients were included, of which 157 (57.5%) were treated for one liver metastasis (LM). Median follow-up was 41 (12–187) months and associated extrahepatic disease was present in 27% of patients (mainly pulmonary, 65%). After a median of 16 (3–151) months, 197 (72%) patients presented with recurrence. Recurrences were early (
Published: 2018
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37. Post-operative complications in elderly onset inflammatory bowel disease: a population-based study

Author: Alexandre Louvet, Corinne Gower, Frederic Gottrand, Vincent Hautefeuille, Guillaume Savoye, David Seguy, Dominique Turck, Benjamin Pariente, Maria Nachury, Pierre DESREUMAUX, Laurent Peyrin-biroulet, Sebastien DHARANCY, Laurent Michaud, Registre EPIMAD, CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Amiens-Picardie-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Normandie Université (NU), 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), Service d'Epidémiologie et de Santé Publique [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Maison Régionale de la Recherche Clinique [Lille], CHU Amiens-Picardie, Hôpital privé Arras les Bonnettes, Hôpital Claude Huriez [Lille], CHU Lille, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), This work is issued from the Epimad Registry. EPIMAD is supported by the Institut National de la Santé et de la Recherche Médicale (INSERM) and the Agence, Santé Publique, France and also received financial support from the François Aupetit Association. This study was funded in part by a grant from the Prgogramme Hospitalier de Recherche Clinique 2010., and The authors wish to thank the interviewing practitioners who collected the data: N. Guillon, I. Rousseau, A. Pétillon, B. Turck, P. Fosse, S. Auzou, M. Leconte, C. Le Gallo and D. Rime. The authors thank all adult and paediatric gastroenterologists who participated in this study. We also thank for its logistic help the European DigestScience Charity Foundation.
Subjects: Male, MESH: Inflammatory Bowel Diseases/surgery, MESH: Crohn Disease/surgery, MESH: Postoperative Complications/epidemiology, Inflammatory bowel disease, Cohort Studies, Postoperative Complications, 0302 clinical medicine, Crohn Disease, Risk Factors, MESH: Risk Factors, Pharmacology (medical), MESH: Incidence, MESH: Cohort Studies, Digestive System Surgical Procedures, MESH: Aged, MESH: Middle Aged, Incidence, Mortality rate, MESH: Colitis, Ulcerative/surgery, Gastroenterology, Middle Aged, Ulcerative colitis, 3. Good health, MESH: Crohn Disease/epidemiology, 030220 oncology & carcinogenesis, Cohort, Female, 030211 gastroenterology & hepatology, Cohort study, medicine.medical_specialty, MESH: Digestive System Surgical Procedures/methods, MESH: Colitis, Ulcerative/epidemiology, 03 medical and health sciences, Internal medicine, medicine, Humans, Adverse effect, Aged, Retrospective Studies, MESH: Humans, Hepatology, business.industry, MESH: Inflammatory Bowel Diseases/epidemiology, MESH: Retrospective Studies, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Retrospective cohort study, Inflammatory Bowel Diseases, medicine.disease, MESH: Male, Colitis, Ulcerative, Complication, business, MESH: Female
Abstract: Comment in :Editorial: post-operative complications in elderly onset inflammatory bowel disease-what is surgery, what is disease, and what is delay of surgery? [Aliment Pharmacol Ther. 2018]Editorial: post-operative complications in elderly onset inflammatory bowel disease-what is surgery, what is disease, and what is delay of surgery? Authors' reply. [Aliment Pharmacol Ther. 2018]; International audience; BACKGROUND: IBD diagnosed after the age of 60 is increasing. Data on post-operative complications in elderly onset IBD are scarce.AIM: To describe the incidence of and factors associated with post-operative complications in elderly onset IBD, diagnosed after the age of 60.METHODS: Using EPIMAD Cohort (1988-2006), among 841 incident IBD patients, 139 (17%) underwent intestinal surgery, including 100 Crohn's disease (CD) and 39 ulcerative colitis (UC).RESULTS: After a median post-operative follow-up of 6 years (2-10), 50 (36%) patients experienced at least 1 complication with a total of 69. During the first 30 post-operative days, the mortality rate was 4%. Thirty-two early complications (grade 2) without significant difference between CD and UC (P = 0.28). Thirty-seven long-term adverse effects of surgical therapy (≥30 days) were observed in 33 patients (24%). Multivariate analysis found (1) acute severe colitis (OR = 7.84 [2.15-28.52]) and emergency surgery (OR = 4.46 [1.75-11.36]) were associated with early post-operative complications, and (2) Female gender (HR = 2.10 [1.01-4.37]) and delay before surgery >3 months (HR = 2.09 [1.01-4.31]) with long-term adverse effects of surgical therapy.CONCLUSIONS: One-third of elderly IBD patients experienced at least 1 post-operative complication. Half of the early complications were severe, and infectious. Emergency surgery was the key driver for post-operative complication.
Published: 2018
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38. Dramatic Increase in Incidence of Ulcerative Colitis and Crohn's Disease (1988–2011): A Population-Based Study of French Adolescents

Author: Silvia Ghione, Hélène Sarter, Mathurin Fumery, Laura Armengol-Debeir, Guillaume Savoye, Delphine Ley, Claire Spyckerelle, Benjamin Pariente, Laurent Peyrin-Biroulet, Dominique Turck, Corinne Gower-Rousseau, J M Andre, M Antonietti, A Aouakli, A Armand, I Aroichane, F Assi, J P Aubet, E Auxenfants, F Ayafi-Ramelot, D Bankovski, B Barbry, N Bardoux, P Baron, A Baudet, B Bazin, A Bebahani, J P Becqwort, V Benet, H Benali, C Benguigui, Ben E Soussan, A Bental, I Berkelmans, J Bernet, K Bernou, C Bernou-Dron, P Bertot, N Bertiaux-Vandaële, V Bertrand, E Billoud, N Biron, B Bismuth, M Bleuet, F Blondel, V Blondin, P Bohon, E Boniface, P Bonnière, E Bonvarlet, P Bonvarlet, A Boruchowicz, R Bostvironnois, M Boualit, B Bouche, C Boudaillez, C Bourgeaux, M Bourgeois, A Bourguet, A Bourienne, J Branche, G Bray, F Brazier, P Breban, H Brihier, V Brung-Lefebvre, P Bulois, P Burgiere, J Butel, J Y Canva, V Canva-Delcambre, J P Capron, F Cardot, P Carpentier, E Cartier, J F Cassar, M Cassagnou, J F Castex, P Catala, S Cattan, S Catteau, B Caujolle, G Cayron, C Chandelier, M Chantre, J Charles, T Charneau, M Chavance-Thelu, D Chirita, A Choteau, J F Claerbout, P Y Clergue, H Coevoet, G Cohen, R Collet, J F Colombel, S Coopman, J Corvisart, A Cortot, F Couttenier, J F Crinquette, V Crombe, I Dadamessi, V Dapvril, T Davion, S Dautreme, J Debas, N Degrave, F Dehont, C Delatre, R Delcenserie, O Delette, T Delgrange, L Delhoustal, J S Delmotte, S Demmane, G Deregnaucourt, P Descombes, J P Desechalliers, P Desmet, P Desreumaux, G Desseaux, P Desurmont, A Devienne, E Devouge, M Devred, A Devroux, A Dewailly, S Dharancy, A Di Fiore, D Djeddi, R Djedir, M L Dreher-Duwat, R Dubois, C Dubuque, P Ducatillon, J Duclay, B Ducrocq, F Ducrot, P Ducrotte, A Dufilho, C Duhamel, D Dujardin, C Dumant-Forest, J L Dupas, F Dupont, Y Duranton, A Duriez, K El Achkar, M El Farisi, C Elie, M C Elie-Legrand, A Elkhaki, M Eoche, D Evrard, J P Evrard, A Fatome, B Filoche, L Finet, M Flahaut, C Flamme, D Foissey, P Fournier, M C Foutrein-Comes, P Foutrein, D Fremond, T Frere, M Fumery, P Gallet, C Gamblin, P S Ganga-Zandzou, R Gérard, G Geslin, Y Gheyssens, N Ghossini, S Ghrib, T Gilbert, B Gillet, D Godard, P Godard, J M Godchaux, R Godchaux, G Goegebeur, O Goria, F Gottrand, P Gower, B Grandmaison, M Groux, C Guedon, J F Guillard, L Guillem, F Guillemot, D Guimber, B Haddouche, S Hakim, D Hanon, V Hautefeuille, P Heckestweiller, G Hecquet, J P Hedde, H Hellal, P E Henneresse, B Heyman, M Heraud, S Herve, P Hochain, L Houssin-Bailly, P Houcke, B Huguenin, S Iobagiu, A Ivanovic, I Iwanicki-Caron, E Janicki, M Jarry, J Jeu, J P Joly, C Jonas, F Katherin, A Kerleveo, A Khachfe, A Kiriakos, J Kiriakos, O Klein, M Kohut, R Kornhauser, D Koutsomanis, J E Laberenne, G Laffineur, M Lagarde, P Lannoy, J Lapchin, M Lapprand, D Laude, R Leblanc, P Lecieux, N Leclerc, C Le Couteulx, J Ledent, J Lefebvre, P Lefiliatre, C Legrand, A Le Grix, P Lelong, B Leluyer, C Lenaerts, L Lepileur, A Leplat, E Lepoutre-Dujardin, H Leroi, M Y Leroy, J P Lesage, X Lesage, J Lesage, I Lescanne-Darchis, J Lescut, D Lescut, B Leurent, P Levy, M Lhermie, A Lion, B Lisambert, F Loire, S Louf, A Louvet, M Luciani, D Lucidarme, J Lugand, O Macaigne, D Maetz, D Maillard, H Mancheron, O Manolache, A B Marks-Brunel, R Marti, F Martin, G Martin, E Marzloff, P Mathurin, J Mauillon, V Maunoury, J L Maupas, B Mesnard, P Metayer, L Methari, B Meurisse, F Meurisse, L Michaud, X Mirmaran, P Modaine, A Monthe, L Morel, P E Mortier, E Moulin, O Mouterde, J Mudry, M Nachury, N'Guyen E Khac, B Notteghem, V Ollevier, A Ostyn, A Ouraghi, D Ouvry, B Paillot, N Panien-Claudot, C Paoletti, A Papazian, B Parent, B Pariente, J C Paris, P Patrier, L Paupart, B Pauwels, M Pauwels, R Petit, M Piat, S Piotte, C Plane, B Plouvier, E Pollet, P Pommelet, D Pop, C Pordes, G Pouchain, P Prades, A Prevost, J C Prevost, B Quesnel, A M Queuniet, J F Quinton, A Rabache, P Rabelle, G Raclot, S Ratajczyk, D Rault, V Razemon, N Reix, M Revillon, C Richez, P Robinson, J Rodriguez, J Roger, J M Roux, A Rudelli, A Saber, G Savoye, P Schlosseberg, M Segrestin, D Seguy, M Serin, A Seryer, F Sevenet, N Shekh, J Silvie, V Simon, C Spyckerelle, N Talbodec, A Techy, J L Thelu, A Thevenin, H Thiebault, J Thomas, J M Thorel, G Tielman, M Tode, J Toisin, J Tonnel, J Y Touchais, Y Touze, J L Tranvouez, C Triplet, D Turck, S Uhlen, E Vaillant, C Valmage, D Vanco, H Vandamme, E Vanderbecq, Vander E Eecken, P Vandermolen, P Vandevenne, L Vandeville, A Vandewalle, C Vandewalle, P Vaneslander, J P Vanhoove, A Vanrenterghem, P Varlet, I Vasies, G Verbiese, G Vernier-Massouille, P Vermelle, C Verne, P Vezilier-Cocq, B Vigneron, M Vincendet, J Viot, Y M Voiment, A Wacrenier, L Waeghemaecker, J Y Wallez, M Wantiez, F Wartel, J Weber, J L Willocquet, N Wizla, E Wolschies, A Zalar, B Zaouri, A Zellweger, C Ziade, Hôpital Jeanne de Flandre [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), Service d'Epidémiologie et de Santé Publique [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Registre EPIMAD, CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Amiens-Picardie-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], CHU Amiens-Picardie, Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Unité Pédiatrique [Saint-Vincent de Paul Lille], Hôpital Saint-Vincent de Paul, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, and Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_specialty, Adolescent, Population, MEDLINE, Disease, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Internal medicine, medicine, Humans, Colitis, Child, education, ComputingMilieux_MISCELLANEOUS, Crohn's disease, education.field_of_study, Hepatology, business.industry, Incidence, Incidence (epidemiology), Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Inflammatory Bowel Diseases, medicine.disease, Ulcerative colitis, digestive system diseases, 3. Good health, Population based study, 030220 oncology & carcinogenesis, Colitis, Ulcerative, Female, 030211 gastroenterology & hepatology, France, business
Abstract: Few data are available to describe the changes in incidence of pediatric-onset inflammatory bowel disease (IBD). The aim of this study was to describe changes in incidence and phenotypic presentation of pediatric-onset IBD in northern France during a 24-year period.Pediatric-onset IBD (17 years) was issued from a population-based IBD study in France between 1988 and 2011. Age groups and digestive location were defined according to the Paris classification.1,350 incident cases were recorded (8.3% of all IBD) including 990 Crohn's disease (CD), 326 ulcerative colitis (UC) and 34 IBD unclassified (IBDU). Median age at diagnosis was similar in CD (14.4 years (Q1=11.8-Q3=16.0)) and UC (14.0 years (11.0-16.0)) and did not change over time. There were significantly more males with CD (females/males=0.82) than UC (females/males=1.25) (P=0.0042). Median time between onset of symptoms and IBD diagnosis was consistently 3 months (1-6). Mean incidence was 4.4/10In this population-based study, CD and UC incidences increased dramatically in adolescents across a 24-year span, suggesting that one or more strong environmental factors may predispose this population to IBD.
Published: 2018
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39. Evaluation of laboratory tests for cirrhosis and for alcohol use, in the context of alcoholic cirrhosis

Author: Whitfield, John B., Masson, Steven, Liangpunsakul, Suthat, Hyman, Jessica, Mueller, Sebastian, Aithal, Guruprasad, Eyer, Florian, Gleeson, Dermot, Thompson, Andrew, Stickel, Felix, Soyka, Michael, Daly, Ann K., Cordell, Heather J., Liang, Tiebing, Foroud, Tatiana, Lumeng, Lawrence, Pirmohamed, Munir, Nalpas, Bertrand, Bence, Camille, Jacquet, Jean-Marc, Louvet, Alexandre, Moirand, Romain, Nahon, Pierre, Naveau, Sylvie, Perney, Pascal, Podevin, Philippe, Haber, Paul S., Seitz, Helmut K., Day, Christopher P., Mathurin, Philippe, Morgan, Timothy M., Seth, Devanshi, Consortium, Genomalc, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Antoine Béclère, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Liver Cirrhosis, Male, Pathology, Alcoholic liver disease, Health (social science), Cirrhosis, [SDV]Life Sciences [q-bio], Toxicology, Biochemistry, Gastroenterology, Behavioral Neuroscience, Liver disease, 0302 clinical medicine, Liver Function Tests, Liver Cirrhosis, Alcoholic, Risk Factors, Ascites, Medicine, Abstinence, medicine.diagnostic_test, Alcohol Abstinence, gamma-Glutamyltransferase, General Medicine, Middle Aged, Alcoholic, 3. Good health, Europe, Neurology, Area Under Curve, Predictive value of tests, Female, 030211 gastroenterology & hepatology, medicine.symptom, Alcohol, Adult, medicine.medical_specialty, Alcohol Drinking, Context (language use), Aspartate aminotransferase, Article, 03 medical and health sciences, Sex Factors, Predictive Value of Tests, Internal medicine, Humans, Aspartate Aminotransferases, International Normalized Ratio, Gamma glutamyl transferase, business.industry, Reproducibility of Results, Bilirubin, Clinical Enzyme Tests, medicine.disease, United States, ROC Curve, Case-Control Studies, business, Liver function tests, Biomarkers, 030217 neurology & neurosurgery
Abstract: International audience; Laboratory tests can play an important role in assessment of alcoholic patients, including for evaluation of liver damage and as markers of alcohol intake. Evidence on test performance should lead to better selection of appropriate tests and improved interpretation of results. We compared laboratory test results from 1578 patients between cases (with alcoholic cirrhosis; 753 men, 243 women) and controls (with equivalent lifetime alcohol intake but no liver disease; 439 men, 143 women). Comparisons were also made between 631 cases who had reportedly been abstinent from alcohol for over 60 days and 364 who had not. ROC curve analysis was used to estimate and compare tests' ability to distinguish patients with and without cirrhosis, and abstinent and drinking cases. The best tests for presence of cirrhosis were INR and bilirubin, with areas under the ROC curve (AUCs) of 0.91~\textpm~0.01 and 0.88~\textpm~0.01, respectively. Confining analysis to patients with no current or previous ascites gave AUCs of 0.88~\textpm~0.01 for INR and 0.85~\textpm~0.01 for bilirubin. GGT and AST showed discrimination between abstinence and recent drinking in patients with cirrhosis, including those without ascites, when appropriate (and for GGT, sex-specific) limits were used. For AST, a cut-off limit of 85~units/L gave 90% specificity and 37% sensitivity. For GGT, cut-off limits of 288~units/L in men and 138~units/L in women gave 90% specificity for both and 40% sensitivity in men, 63% sensitivity in women. INR and bilirubin show the best separation between patients with alcoholic cirrhosis (with or without ascites) and control patients with similar lifetime alcohol exposure. Although AST and GGT are substantially increased by liver disease, they can give useful information on recent alcohol intake in patients with alcoholic cirrhosis when appropriate cut-off limits are used.
Published: 2018
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40. Teaching NeuroImages: Cytotoxic lesions of the corpus callosum in encephalopathic patients with COVID-19

Author: Robert-Yves Carlier, Caroline Diffre, Martin Louvet, Christophe Leveque, Djillali Annane, Myriam Edjlali, Morgan Matt, D. Orlikowski, Aurélie Le Gal, HAL UVSQ, Équipe, Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Raymond Poincaré [AP-HP], and Hôpital privé de Parly-2
Subjects: Male, Pathology, medicine.medical_specialty, Subarachnoid hemorrhage, Splenium, Corpus callosum, Corpus Callosum, law.invention, Lesion, 03 medical and health sciences, 0302 clinical medicine, law, Humans, Medicine, Cytotoxic T cell, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Brain Diseases, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, medicine.diagnostic_test, business.industry, COVID-19, Magnetic resonance imaging, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Intensive care unit, Hyperintensity, 3. Good health, Diffusion Magnetic Resonance Imaging, Neurology (clinical), medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract: Two men, aged 49 and 51 years, with acute encephalopathy and rapid clinical deterioration were transferred to the intensive care unit. Both were recently tested positive for coronavirus disease 2019 on nasopharyngeal swab. On brain MRI, a lesion of the splenium of the corpus callosum was found, with T2-FLAIR hyperintensity and restricted diffusion (figure). This pattern is characteristic of cytotoxic lesion of the corpus callosum, an entity described previously as secondary to an underlying cause such as infection, drug toxicity, subarachnoid hemorrhage, history of CNS malignancy, or metabolic disorders.1 These lesions are nonischemic lesions, usually transient and reversible on follow-up. The underlying mechanism relies on the vulnerability of the splenium of the corpus callosum to cytokinopathy.
Published: 2020
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41. A brief diversity training: Raising awareness of ingroup privilege to improve attitudes towards disadvantaged outgroups

Author: Franziska Ehrke, Aysan Ashoee, Eva Louvet, Melanie C. Steffens, Laboratoire de Psychologie des Cognitions (LPC), and Université de Strasbourg (UNISTRA)
Subjects: Adult, Male, Adolescent, media_common.quotation_subject, [SHS.PSY]Humanities and Social Sciences/Psychology, 050109 social psychology, Vulnerable Populations, 050105 experimental psychology, Young Adult, Diversity training, Arts and Humanities (miscellaneous), Humans, 0501 psychology and cognitive sciences, 10. No inequality, General Psychology, Prejudice (legal term), media_common, Oppression, Social Identification, 4. Education, 05 social sciences, General Medicine, Ingroups and outgroups, Disadvantaged, Attitude, Feeling, Outgroup, Female, Psychology, Social psychology, Privilege (social inequality)
Abstract: Diversity training is a popular strategy to reduce prejudice within educational settings. However, in practice, diversity training rarely relies on social-psychological theory, and research on its effectiveness in real-world settings is scarce. Previous research regarding diversity training has particularly neglected an important theoretical concept: privilege as the counterpart of discrimination. Therefore, we developed a diversity training aiming to increase awareness of ingroup privilege, using an intersectional approach to teach participants the complex interaction between privilege and oppression. We randomly allocated students of educational science (N = 112) to a repeated-measures (pre-test, post-test, follow-up) control-group design. Compared with the control group, training participants showed a significant increase in awareness of ingroup privilege 1 week after the training, whereas there was no change in awareness of discrimination. Furthermore, increased awareness of ingroup privilege 1 week after the training mediated improved outgroup attitudes (i.e., more positive outgroup feelings towards immigrants and refugees, reduced subtle prejudice towards immigrants and reduced homonegativity) 2 weeks after the training.
Published: 2020
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42. Characterization of Rat ILCs Reveals ILC2 as the Dominant Intestinal Subset

Author: Ahmed Abidi, Thomas Laurent, Gaëlle Bériou, Laurence Bouchet-Delbos, Cynthia Fourgeux, Cédric Louvet, Raja Triki-Marrakchi, Jeremie Poschmann, Régis Josien, Jérôme Martin, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université de Tunis - El Manar II, Université de Tunis El Manar (UTM), École Centrale de Nantes (ECN), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d’Immunologie, Centre d’Immunomonitorage Nantes Atlantique (CIMNA), Centre hospitalier universitaire de Nantes (CHU Nantes), This work was realized in the context of IHU-CESTI project that received French government financial support managed by the National Research Agency (ANR). This work was also supported by the Région Pays de la Loire. AA was supported by a FrenchTunisian PHU-UTIQUE grant from the 2015 Hubert Curien program (CMCU N◦15G0809)., ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010), Le Bihan, Sylvie, Instituts Hospitalo-Universitaires B - Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU) - - CESTI (TSI-IHU)2010 - ANR-10-IBHU-0005 - IBHU - VALID, and University of Tunis El Manar
Subjects: Male, 0301 basic medicine, lcsh:Immunologic diseases. Allergy, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Immunology, innate lymphoid cells, Cell Count, Biology, Flow cytometry, ILC2, Rats, Sprague-Dawley, Mice, 03 medical and health sciences, Th2 Cells, 0302 clinical medicine, Intestinal mucosa, medicine, Animals, Humans, Immunology and Allergy, Mesenteric lymph nodes, rat, Lymphocytes, Intestinal Mucosa, Receptor, skin and connective tissue diseases, intestine, Cells, Cultured, Original Research, medicine.diagnostic_test, Innate lymphoid cell, Flow Cytometry, Phenotype, Immunity, Innate, Lymphocyte Subsets, Rats, Cell biology, Peyer Patch, [SDV] Life Sciences [q-bio], body regions, 030104 developmental biology, medicine.anatomical_structure, Cytokine, secondary lymphoid organs, Cytokines, lcsh:RC581-607, 030215 immunology
Abstract: International audience; Innate lymphoid cells (ILCs) are tissue-resident lymphocytes that lack antigen-specific receptors and exhibit innate effector functions such as cytokine production that play an important role in immediate responses to pathogens especially at mucosal sites. Mouse and human ILC subsets have been extensively characterized in various tissues and in blood. In this study, we present the first characterization of ILCs and ILC subsets in rat gut and secondary lymphoid organs using flow cytometry and single cell RNA sequencing. Our results show that phenotype and function of rat ILC subsets are conserved as compared to human and mouse ILCs. However, and in contrast to human and mouse, our study unexpectedly revealed that ILC2 and not ILC3 was the dominant ILC subset in the rat intestinal lamina propria. ILC2 predominance in the gut was independent of rat strain, sex or housing facility. In contrast, ILC3 was the predominant ILC subset in mesenteric lymph nodes and Peyer patches. In conclusion, our study demonstrates that in spite of highly conserved phenotype and function between mice, rat and humans, the distribution of ILC subsets in the intestinal mucosa is dependent on the species likely in response to both genetic and environmental factors.
Published: 2020
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43. Prognostic Value of Tumor Deposits for Disease-Free Survival in Patients With Stage III Colon Cancer: A Post Hoc Analysis of the IDEA France Phase III Trial (PRODIGE-GERCOR)

Author: Jérôme Dauba, S. Fratte, Olivier Dupuis, Julien Taieb, Jean-François Emile, Frédéric Bibeau, Jean François Delattre, Yves Becouarn, Magali Svrcek, Romain Cohen, Dewi Vernerey, Benoist Chibaudel, Julie Henriques, Antoine Falcoz, Christophe Louvet, Thierry André, 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Hôpital Ambroise Paré [AP-HP], Hôpital Nord Franche-Comté [Hôpital de Trévenans] (HNFC), Service d'Oncologie Médicale [Institut Hospitalier Franco-Britannique], Division of Medical Oncology - Institut Hospitalier Franco-Britannique, CHU Mont de Marsan, Service d'Oncologie médicale [Clinique Victor Hugo], Clinique Victor Hugo, Institut Bergonié [Bordeaux], UNICANCER, Département de Pathologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), 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), Service d'Oncologie Médicale [Montsouris], Institut Mutualiste de Montsouris (IMM), and Service de Pathologie [CHU Saint-Antoine]
Subjects: Oncology, Male, Cancer Research, medicine.medical_specialty, Disease free survival, Colorectal cancer, [SDV]Life Sciences [q-bio], TNM staging system, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Post-hoc analysis, medicine, Humans, In patient, 030212 general & internal medicine, Aged, Neoplasm Staging, business.industry, Cancer, Middle Aged, medicine.disease, Prognosis, 3. Good health, Stage III Colon Cancer, 030220 oncology & carcinogenesis, Colonic Neoplasms, Female, business
Abstract: PURPOSE Tumor deposits (TDs) seem to affect the prognosis of patients with colon cancer (CC). In the seventh edition of the American Joint Committee on Cancer TNM staging system for CC, the presence of TDs is only considered in the absence of lymph node metastases (LNMs). In the era of personalized duration of histopathologic criteria-based adjuvant therapy, this could potentially lead to a decrease in the prognostic prediction accuracy. PATIENTS AND METHODS A post hoc analysis of all pathologic reports from patients with stage III CC included in the IDEA France phase III study (ClinicalTrials.gov identifier: NCT00958737 ) investigating the duration of adjuvant fluorouracil, leucovorin, and oxaliplatin or capecitabine and oxaliplatin therapy (3 v 6 months) was performed. The primary objective was to determine the prognostic impact of TD on disease-free survival (DFS). The effect of the addition of TD to LNM count on pN restaging was also evaluated. A multivariable analysis was performed to establish the association between TD and DFS. RESULTS Of 1,942 patients, 184 (9.5%) had TDs. The pN1a/b and pN1c populations showed similar DFS. TD-positive patients had worse prognosis compared with TD-negative patients, with 3-year DFS rates of 65.6% (95% CI, 58.0% to 72.1%) and 74.7% (95% CI, 72.6% to 76.7%; P = .0079), respectively. On multivariable analysis, TDs were associated with a higher risk of recurrence or death (hazard ratio [HR], 1.36; P = .0201). Other adverse factors included pT4 and/or pN2 disease (HR, 2.21; P < .001), the 3 months of adjuvant treatment (HR, 1.29; P = .0029), tumor obstruction (HR, 1.28; P = .0233), and male sex (HR, 1.24; P = .0151). Patients restaged as having pN2 disease (n = 35, 2.3%) had similar DFS as patients initially classified as pN2. CONCLUSION The presence of TDs is an independent prognostic factor for DFS in patients with stage III CC. The addition of TD to LNM may help to better define the duration of adjuvant therapy.
Published: 2020
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44. Erythrocyte-encapsulated asparaginase (eryaspase) combined with chemotherapy in second-line treatment of advanced pancreatic cancer: An open-label, randomized Phase IIb trial

Author: Olivier Bouché, Iman El Hariry, Thierry Lecomte, Thierry André, David Tougeron, Jérôme Cros, Adam Hamm, Jean-Baptiste Bachet, Jean-Philippe Metges, Christine Rebischung, Pascal Hammel, Laurent Mineur, Christophe Tournigand, Christophe Louvet, Farid El Hajbi, Portales Fabienne, Richard Kay, Rosine Guimbaud, Anu Gupta, Roger Faroux, Christelle De La Fouchardiere, Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Sainte Catherine [Avignon], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Centre Léon Bérard [Lyon], Service d'Oncologie Médicale [Montsouris], Institut Mutualiste de Montsouris (IMM), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Service de chirurgie digestive (CH de La Roche-sur-Yon), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service d'Oncologie médicale [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor [Créteil], 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), CHU Pitié-Salpêtrière [AP-HP], Université Lille Nord de France (COMUE)-UNICANCER, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Service de gastroentérologie et cancérologie digestive [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Saint-Antoine [APHP], CRLCC Oscar Lambret, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, Cancer Research, Organoplatinum Compounds, Survival, medicine.medical_treatment, Biopsy, Leucovorin, Kaplan-Meier Estimate, Gastroenterology, Deoxycytidine, chemistry.chemical_compound, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Aged, 80 and over, 0303 health sciences, Middle Aged, Progression-Free Survival, 3. Good health, Erythrocyte, Oncology, 030220 oncology & carcinogenesis, Adenocarcinoma, Female, Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor, Fluorouracil, medicine.drug, Adult, Asparaginase, medicine.medical_specialty, Neutropenia, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Pancreatic cancer, Internal medicine, medicine, Humans, Adverse effect, Pancreas, Response Evaluation Criteria in Solid Tumors, 030304 developmental biology, Aged, Neoplasm Staging, Chemotherapy, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Gemcitabine, PHASE IIB TRIAL, Pancreatic Neoplasms, chemistry, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business, Pancreatic adenocarcinoma, Follow-Up Studies, Asparagine synthetase
Abstract: International audience; PURPOSE: This Phase IIb (NCT02195180) open-label study evaluated erythrocyte-encapsulated asparaginase (eryaspase) in combination with chemotherapy in second-line advanced pancreatic adenocarcinoma.METHODS: Eligible patients were randomized 2:1 to either eryaspase in combination with gemcitabine or mFOLFOX6 (eryaspase arm), or to gemcitabine or mFOLFOX6 alone (control arm). Co-primary endpoints were overall survival (OS) and progression-free survival (PFS) in patients with low asparagine synthetase (ASNS) expression. Secondary endpoints included OS and PFS in the entire population.RESULTS: 141 patients were randomized (eryaspase arm, n = 95; control arm, n = 46). Median OS and PFS in patients with low ASNS expression were 6.2 months (95% CI, 5.1-8.8) in the eryaspase arm versus 4.9 months (3.1-7.1) in the control arm (HR, 0.63; 95% CI, 0.39-1.01; P = 0.056) and 2.0 months (95% CI, 1.8-3.4) in the eryaspase arm versus 1.8 months (1.4-3.8) in the control arm (HR, 0.67; 95% CI, 0.40-1.12; P = 0.127), respectively. In the entire population, median OS and PFS for the eryaspase arm versus control were 6.0 months versus 4.4 months (HR, 0.60; P = 0.008) and 2.0 months versus 1.6 months (HR, 0.56; 95% CI, 0.37-0.84; P = 0.005), respectively. The combination of eryaspase and chemotherapy was well tolerated. The most frequent Grade 3/4 adverse events in the eryaspase arm (n = 93) were gamma-glutamyltransferase increase (16 [17.2%]), neutropenia (12 [12.9%]), and physical health deterioration (12 [12.9%]).CONCLUSION: Eryaspase in combination with chemotherapy is associated with improvements in OS and PFS, irrespective of ASNS expression in second-line advanced pancreatic adenocarcinoma. A Phase III trial is underway.
Published: 2020
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45. Intestinal Fungal Dysbiosis and Systemic Immune Response to Fungi in Patients With Alcoholic Hepatitis

Author: Juan Caballería, Michael R. Lucey, Meritxell Ventura-Cots, Alexandre Louvet, Claire Kuelbs, Xin M. Tu, Jinyuan Liu, Sonja Lang, Francisco Bosques-Padilla, Derrick E. Fouts, Ramon Bataller, Debbie L. Shawcross, Elizabeth C. Verna, Peter Stärkel, Juan G. Abraldes, José Altamirano, Manolito Torralba, Robert S. Brown, Yi Duan, Victor Vargas, Guadalupe Garcia-Tsao, Bernd Schnabl, Samuel B. Ho, Philippe Mathurin, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, and UCL - (SLuc) Service de gastro-entérologie
Subjects: 0301 basic medicine, Adult, Male, Alcoholic liver disease, Mycobiota, medicine.medical_specialty, medicine.drug_class, Antibiotics, Alcoholic hepatitis, Alcohol use disorder, Saccharomyces cerevisiae, Gastroenterology, Article, Cohort Studies, 03 medical and health sciences, Liver disease, Immune System Phenomena, 0302 clinical medicine, Internal medicine, medicine, Humans, Antibodies, Fungal, Aged, Candida, Intestinal permeability, Hepatology, business.industry, Hepatitis, Alcoholic, Middle Aged, medicine.disease, Intestines, 030104 developmental biology, Dysbiosis, 030211 gastroenterology & hepatology, Female, business, Mycobiome
Abstract: Chronic alcohol consumption causes increased intestinal permeability and changes in the intestinal microbiota composition, which contribute to the development and progression of alcohol-related liver disease. In this setting, little is known about commensal fungi in the gut. We studied the intestinal mycobiota in a cohort of patients with alcoholic hepatitis, patients with alcohol use disorder, and nonalcoholic controls using fungal-specific internal transcribed spacer amplicon sequencing of fecal samples. We further measured serum anti-Saccharomyces cerevisiae antibodies (ASCA) as a systemic immune response to fungal products or fungi. Candida was the most abundant genus in the fecal mycobiota of the two alcohol groups, whereas genus Penicillium dominated the mycobiome of nonalcoholic controls. We observed a lower diversity in the alcohol groups compared with controls. Antibiotic or steroid treatment was not associated with a lower diversity. Patients with alcoholic hepatitis had significantly higher ASCA levels compared to patients with alcohol use disorder and to nonalcoholic controls. Within the alcoholic hepatitis cohort, patients with levels of at least 34 IU/mL had a significantly lower 90-day survival (59%) compared with those with ASCA levels less than 34 IU/mL (80%) with an adjusted hazard ratio of 3.13 (95% CI, 1.11-8.82; P = 0.031). Conclusion: Patients with alcohol-associated liver disease have a lower fungal diversity with an overgrowth of Candida compared with controls. Higher serum ASCA was associated with increased mortality in patients with alcoholic hepatitis. Intestinal fungi may serve as a therapeutic target to improve survival, and ASCA may be useful to predict the outcome in patients with alcoholic hepatitis.
Published: 2020

46. High IGF1R protein expression correlates with disease-free survival of patients with stage III colon cancer

Author: Christèle Desbois-Mouthon, Aziz Zaanan, Claire Calmel, Christophe Louvet, Françoise Praz, Hélène Blons, Julien Taieb, Brice Gayet, Pierre Validire, Yann Parc, Yves Le Bouc, Julie Henriques, Claire Goumard, Magali Svrcek, Fatiha Merabtene, Jean-François Fléjou, 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 chirurgie digestive, générale et cancérologique [CHU HEGP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), 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]), Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de biologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Unité Mixte de Service d'Imagerie et de Cytométrie [CHU Saint-Antoine] (UMS LUMIC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de chirurgie générale et digestive [CHU Saint-Antoine], Institut Mutualiste de Montsouris (IMM), Service de gastroenterologie [CHU HEGP], and Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, Cancer Research, Multivariate analysis, Colorectal cancer, Kaplan-Meier Estimate, Gastroenterology, Receptor, IGF Type 1, 0302 clinical medicine, IGF1R, Stage (cooking), Receptor, Aged, 80 and over, Reverse Transcriptase Polymerase Chain Reaction, General Medicine, Middle Aged, Immunohistochemistry, 3. Good health, Colon cancer, Gene Expression Regulation, Neoplastic, Oncology, 030220 oncology & carcinogenesis, Colonic Neoplasms, Molecular Medicine, Female, Adult, medicine.medical_specialty, IGF-II/IGF2, Disease-free survival, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, RNA, Messenger, MSI, Insulin-like growth factor 1 receptor, Aged, Neoplasm Staging, Retrospective Studies, Proportional hazards model, business.industry, Retrospective cohort study, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, KRAS/BRAF, body regions, 030104 developmental biology, business
Abstract: International audience; Purpose: The aim of this study was to investigate the association between expression of insulin-like growth factor-1 receptor (IGF1R) and its ligand, IGF-II, and disease-free survival (DFS) in patients with stage III colon cancer (CC).Methods: In this retrospective study we included consecutive patients who underwent curative surgery for stage III CC. IGF1R and IGF-II/IGF2 status were evaluated in tumour samples by immunohistochemistry and quantitative real-time PCR (qRT-PCR). Associations of markers with DFS were analysed using Cox proportional hazards models.Results: Hundred and fifty-one CC patients were included (median age, 66.6 years; female, 54.3%). Low levels of IGF1R and IGF-II protein expression were observed in 16.1% and 10.7% of the cases, respectively. No significant differences in clinicopathological characteristics between patients with tumours expressing low IGF1R or IGF-II protein levels and those with high levels were observed. A low IGF1R protein expression was found to be significantly associated with a shorter DFS (HR 3.32; 95% CI, 1.7-6.31; p = 0.0003), while no association was observed between IGF-II protein expression and DFS (HR 0.91; 95% CI, 0.28-2.96; p = 0.87). In a multivariate analysis, IGF1R protein status remained an independent prognostic factor for DFS (HR 2.73; 95% CI, 1.40-5.31; p = 0.003). Furthermore, we found that neither IGF1R nor IGF2 mRNA expression levels as measured by qRT-PCR correlated with the respective protein expression levels as assessed by immunohistochemistry. Neither of the mRNA expression levels was significantly associated with DFS.Conclusions: From our data we conclude that low IGF1R protein expression represents a poor prognostic biomarker in stage III colon cancer.
Published: 2020
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47. Intestinal Virome in Patients With Alcoholic Hepatitis

Author: Meritxell Ventura-Cots, Derrick E. Fouts, Elizabeth C. Verna, David T. Pride, Tatiana Kisseleva, Michael R. Lucey, Robert S. Brown, Jessica Chopyk, Samuel B. Ho, Alexandre Louvet, Bernd Schnabl, Bei Gao, Juan Caballería, Francisco Bosques-Padilla, Ramon Bataller, Guadalupe Garcia-Tsao, Xin M. Tu, Philippe Mathurin, Leila K. Schwanemann, Xinlian Zhang, David A. Brenner, Victor Vargas, Debbie L. Shawcross, Juan G. Abraldes, Lu Jiang, Peter Stärkel, José Altamirano, Sonja Lang, Yi Duan, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, and UCL - (SLuc) Service de gastro-entérologie
Subjects: 0301 basic medicine, Liver Cirrhosis, Male, Antibiotics, Medical Biochemistry and Metabolomics, medicine.disease_cause, Gastroenterology, Severity of Illness Index, Oral and gastrointestinal, Parvoviridae, Hepatitis, Liver disease, Alcohol Use and Health, Substance Misuse, Feces, 0302 clinical medicine, Medicine, Bacteriophages, Viral, Intestinal Mucosa, Herpesviridae, Virome, Liver Disease, Middle Aged, Alcoholic, Survival Rate, Alcoholism, Liver, RNA, Viral, 030211 gastroenterology & hepatology, Female, Infection, Adult, medicine.medical_specialty, medicine.drug_class, Chronic Liver Disease and Cirrhosis, Clinical Sciences, Immunology, Alcoholic hepatitis, Article, End Stage Liver Disease, 03 medical and health sciences, Clinical Research, Internal medicine, Animals, Humans, Human virome, Microbiome, Aged, Hepatology, Gastroenterology & Hepatology, business.industry, Hepatitis, Alcoholic, Case-control study, DNA, medicine.disease, 030104 developmental biology, Good Health and Well Being, Case-Control Studies, DNA, Viral, RNA, Metagenomics, business, Digestive Diseases
Abstract: Alcoholic hepatitis is a severe manifestation of alcohol-associated liver disease with high mortality. Although gut bacteria and fungi modulate disease severity, little is known about the effects of the viral microbiome (virome) in patients with alcohol-associated liver disease. We extracted virus-like particles from 89 patients with alcoholic hepatitis who were enrolled in a multicenter observational study, 36 with alcohol use disorder, and 17 individuals without alcohol use disorder (controls). Virus-like particles from fecal samples were fractionated using differential filtration techniques and metagenomic sequencing was performed to characterize intestinal viromes. We observed an increased viral diversity in fecal samples from patients with alcohol-associated liver disease, with the most significant changes in samples from patients with alcoholic hepatitis. Escherichia-, Enterobacteria-, and Enterococcus phages were overrepresented in fecal samples from patients with alcoholic hepatitis, along with significant increases in mammalian viruses such as Parvoviridae and Herpesviridae. Antibiotic treatment was associated with higher viral diversity. Specific viral taxa, such as Staphylococcus phages and Herpesviridae, were associated with increased disease severity, indicated by a higher median model for end-stage liver disease (MELD) score, and associated with increased 90-day mortality. In conclusion, intestinal viral taxa are altered in fecal samples from patients with alcoholic hepatitis and associated with disease severity and mortality. Our study, for the first time, described an intestinal virome signature associated with alcoholic hepatitis.
Published: 2020

48. Sudden onset of immune-mediated type 1 diabetes mellitus in a 93-year-old woman: a case report

Author: A. Louvet, Philippe Oriot, Ilse Weets, G. Debugne, Pathology/molecular and cellular medicine, Diabetes Pathology & Therapy, and Clinical Biology
Subjects: Adult, Male, Anti GAD, Pediatrics, medicine.medical_specialty, Diabetic ketoacidosis, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Human leukocyte antigen, 030204 cardiovascular system & hematology, Diabetic Ketoacidosis, Anti IA2, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Immune system, Diabetes mellitus, Internal Medicine, Humans, Medicine, Sudden onset type 1 diabetes mellitus, Autoantibodies, Aged, 80 and over, Type 1 diabetes, business.industry, General Medicine, medicine.disease, HLA, Anti gad antibodies, Diabetes Mellitus, Type 1, Type 1 diabetes in elderly, Female, business, Sudden onset
Published: 2018
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49. RECIST and CHOI criteria in the evaluation of tumor response in patients with metastatic colorectal cancer treated with regorafenib, a prospective multicenter study

Author: Olivier Lucidarme, Benoist Chibaudel, Stefano Kim, Benoit Rousseau, Julie Henriques, Mathilde Wagner, Thierry André, Aurélien Gobert, Jean-Baptiste Bachet, Romain Cohen, Marie-Line Garcia-Larnicol, Paul Gillard, Christophe Louvet, Thibault Mazard, Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CIC Pitié BT, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Cooperator Multidisciplinary Oncology Group (GERCOR), CHU Henri Mondor, Institut du Cancer de Montpellier (ICM), Service d'Oncologie Médicale [Montsouris], Institut Mutualiste de Montsouris (IMM), Service d'Oncologie Médicale [Institut Hospitalier Franco-Britannique], Division of Medical Oncology - Institut Hospitalier Franco-Britannique, CHU Saint-Antoine [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 [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: Male, Oncology, Pyridines, Colorectal cancer, Tumor response, 030218 nuclear medicine & medical imaging, chemistry.chemical_compound, 0302 clinical medicine, Choi Criteria, Clinical endpoint, Prospective Studies, Neoplasm Metastasis, Computed tomography, education.field_of_study, Radiological and Ultrasound Technology, General Medicine, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, 030220 oncology & carcinogenesis, Female, Colorectal Neoplasms, Research Article, Adult, lcsh:Medical physics. Medical radiology. Nuclear medicine, medicine.medical_specialty, lcsh:R895-920, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, 03 medical and health sciences, Internal medicine, Regorafenib, medicine, Humans, Radiology, Nuclear Medicine and imaging, In patient, education, Response Evaluation Criteria in Solid Tumors, Aged, business.industry, Phenylurea Compounds, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Multicenter study, chemistry, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Tomography, X-Ray Computed, business
Abstract: Background To evaluate the objective response rate (ORR) at 2 months of treatment with regorafenib according to RECIST 1.1, Choi, and modified Choi (mChoi) criteria in patients with metastatic colorectal cancer (mCRC). Methods Baseline and 2-month contrast-enhanced computed-tomography (CECT) scans of 55 patients with mCRC, prospectively enrolled in phase II TEXCAN trial, were centrally assessed. The primary endpoint was 2-month ORR by RECIST 1.1, Choi, and mChoi criteria. Final outcome was overall survival (OS). Results Of 55 patients included in this study (Intention-to-treat [ITT1] population), 35 had CECT at 2 months (ITT2 population). According to RECIST 1.1 criteria, 20 (57%) patients were SD and 15 were PD (43%) in the ITT2 population. According to Choi criteria, 18 (51%) patients were responders and 17 (48%) were non-responders. Median OS was 5.3 months (95% CI 3.7–8.6) in the ITT1 population and 8.9 months (95% CI 5.1–12.6) in the ITT2 population. In the ITT2 population, median OS was 16 months (95% CI 6.6–17.5) in SD patients (n = 20) and 4.6 months (95% CI 3.3–5.8) in PD patients (n = 15), according to RECIST 1.1 criteria (HR = 6.48). Median OS was 7.9 months (95% CI 4.2–17.5) in responders (n = 18) and 9.9 months (95% CI 3.7-NA) in non-responders (n = 17) according to Choi criteria (HR = 1.06). All patients except one were classified as non-responders with mChoi criteria. Conclusion At 2 months, unlike RECIST 1.1, Choi and mChoi criteria could not identify mCRC patients with regorafenib survival benefit. Trial registration ClinicalTrials.gov Identifier: NCT02699073.Registered March 4, 2016, Retrospectively registered.
Published: 2019
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50. Does the difficulty grade of laparoscopic liver resection for colorectal liver metastases correlate with long-term outcomes?

Author: Wacław Hołówko, Mostefa Bennamoun, Brice Gayet, Ioannis Triantafyllidis, Marc Beaussier, David Fuks, Christophe Louvet, Nicolas Tabchouri, Anthony Sarran, Marine Lefevre, and Maud Neuberg
Subjects: Adult, Male, medicine.medical_specialty, R1 resection, Group ii, 030230 surgery, Disease-Free Survival, Resection, 03 medical and health sciences, 0302 clinical medicine, Overall survival, Long term outcomes, Medicine, Hepatectomy, Humans, In patient, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Liver Neoplasms, Metastasectomy, Margins of Excision, General Medicine, Middle Aged, Margin status, Prognosis, Neoadjuvant Therapy, Surgery, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Female, Laparoscopy, business, Colorectal Neoplasms
Abstract: Introduction Prognosis of patients with colorectal liver metastases (CRLM) is strongly correlated with the oncological outcome after liver resection. The aim of this study was to analyze the impact of laparoscopic liver resection (LLR) difficulty score (IMM difficulty score) on the oncological results in patients treated for CRLM. Methods All patients who underwent LLRs for CRLM from 2000 to 2016 in our department, were retrospectively reviewed. Data regarding difficulty classification, -according to the Institute Mutualiste Montsouris score (IMM)-, recurrence rate, recurrence-free survival (RFS), overall survival (OS) and data regarding margin status were analyzed. Results A total of 520 patients were included. Patients were allocated into 3 groups based on IMM difficulty score of the LLR they underwent: there were 227 (43,6%), 84 (16,2%) and 209 (40,2%) patients in groups I, II and III, respectively. The R1 resection rate in group I, II and III were 8,8% (20/227), 11,9% (10/84) and 12,4% (26/209) respectively (p = 0.841). Three- and 5-year RFS rates were 77% and 73% in group I, 58% and 51% in group II, 61% and 53% in group III, respectively (p = 0.038). Three and 5-year OS rates were 87% and 80% for group I, 77% and 66% for group II, 80% and 69% for group III respectively (p = 0.022). Conclusion The higher LLR difficulty score correlates with significant morbidity and worse RFS and OS, although the more technically demanding and difficult cases are not associated with increased rates of positive resection margins and recurrence.
Published: 2019

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