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1. Assessment of anal sphincter distensibility following the STARR procedure: a pilot study

Author

Valérie Bridoux, Jean-Jacques Tuech, Chloé Melchior, Anne-Marie Leroi, Charlotte Desprez, Guillaume Gourcerol, Estelle Houivet, Service de physiologie digestive, urinaire, respiratoire et de l'exercice [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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Service d'Hépato-Gastroentérologie [CHU Rouen], Service de chirurgie digestive [CHU Rouen], CHU Rouen, Unité de biostatistiques [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), and Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, medicine.medical_specialty, Anal Canal, Pilot Projects, 03 medical and health sciences, 0302 clinical medicine, Refractory, Surgical Stapling, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Medicine, Fecal incontinence, Rectal resection, Defecation, ComputingMilieux_MISCELLANEOUS, Medical treatment, business.industry, Rectocele, Recovery of Function, General Medicine, Middle Aged, Surgical correction, Dilatation, 3. Good health, Surgery, Treatment Outcome, Anal dilatation, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, medicine.symptom, business, Anal sphincter
Abstract

Aim: The STARR (Stapled Trans-Anal Rectal Resection) procedure consists of a surgical correction of symptomatic rectocele refractory to medical treatment, involving anal dilatation. The aim of the ...

Published
2019

2. Is abnormal 25 g fructose breath test a predictor of symptomatic response to a low fructose diet in irritable bowel syndrome?

Author

Mathilde Maccarone, Estelle Houivet, Charlotte Desprez, Laura Armengol Debeir, Laura Bril, Philippe Ducrotté, Chloé Melchior, Emilie Grout, Guillaume Gourcerol, Anne-Marie Leroi, 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), Normandie Université (NU), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Service de physiologie digestive, urinaire, respiratoire et de l'exercice [CHU Rouen], Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de biostatistiques [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Hôpital Charles Nicolle [Rouen], CHU Rouen, and CCSD, Accord Elsevier

Subjects
0301 basic medicine, Male, Fructose malabsorption, Critical Care and Intensive Care Medicine, Gastroenterology, Severity of Illness Index, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Irritable bowel syndrome, Nutrition and Dietetics, medicine.diagnostic_test, digestive, oral, and skin physiology, Low fructose diet, Middle Aged, 3. Good health, Fructose breath test, Breath Tests, Positive test result, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, France, Adult, medicine.medical_specialty, Adolescent, 030209 endocrinology & metabolism, Fructose, 03 medical and health sciences, Young Adult, Predictive Value of Tests, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Aged, Breath test, 030109 nutrition & dietetics, business.industry, Rome iii, medicine.disease, Diet, Clinical trial, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, chemistry, Irritable bowel syndrome-symptom severity score, business, Predictive factor, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Summary Background Fructose malabsorption may trigger gastrointestinal symptoms in irritable bowel syndrome patients and a low fructose diet seems to improve digestive symptoms. Aim The aim of our study was to determine whether fructose malabsorption detected by a 25g fructose breath test could be a predictor of the efficacy of a low fructose diet. Methods 88 patients (73 women, median age, 45.5 years, range 18–69) with irritable bowel syndrome according to Rome III criteria were included in this prospective, controlled study. All 88 patients had a 25 g fructose breath test; 37 had a positive test result defining fructose malabsorption. All 88 patients followed a low fructose diet for 2 weeks, blinded to their test results. Patients filled self validated-questionnaires before and at the end of the dietary period. The main outcome measurement was the Irritable Bowel Syndrome-Symptom Severity Score. Results Irritable Bowel Syndrome-Symptom Severity Score significantly decreased in fructose absorbers and fructose malabsorbers after a low fructose diet (−68.0 [−137; 0] versus −73.5 [−173; −11.5]) with no difference according to fructose breath test result (adjusted P = 0.984). Conclusion A positive 25 g fructose breath test is not a predictor of the efficacy of a low fructose diet in irritable bowel syndrome. Registered clinical trial www.clinicaltrials.gov ( NCT02188680 ).

Published
2020

3. Is there a timing for sensitivity to acute cerebral ischemia in migraine patients?

Author

Benjamin Hebant, Aude Triquenot-Bagan, Ozlem Ozkul-Wermester, Estelle Houivet, Lou Grangeon, Isabelle Francillard, David Maltête, Emmanuel Gerardin, Agathe Cornillot, Evelyne Guegan-Massardier, Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Radiologie [CHU Rouen], Normandie Université (NU)-Normandie Université (NU), Unité de biostatistiques [CHU Rouen], Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-CHU Rouen

Subjects
Male, medicine.medical_specialty, Time Factors, Aura, Migraine Disorders, [SDV]Life Sciences [q-bio], Ischemia, Perfusion scanning, Brain Ischemia, Time-to-Treatment, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, Stroke, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Middle Aged, medicine.disease, 3. Good health, Neurology, Migraine, Case-Control Studies, Cortical spreading depression, Cohort, Infarct volume, Cardiology, Female, Neurology (clinical), Tomography, X-Ray Computed, business, 030217 neurology & neurosurgery
Abstract

Migraine may be a factor of increased cerebral sensitivity to ischemia. Previous studies were conducted within 6 to 72 after stroke onset. We aimed to determine if an accelerated infarct growth exists in migraine patients within the first 4.5 h.A retrospective case-control study was conducted where all patients admitted for acute stroke started4.5 h before and who underwent perfusion CT were assessed. The hypoperfusion and necrosis volumes on initial CT perfusion were analyzed, as well as the final infarct volume on MRI performed within 72 h after admission. A no-mismatch pattern was defined as a ratio necrosis/hypoperfusion volume 83%.24 patients with personal history of migraine were identified, 8 of them with aura. The control cohort included 51 patients. No difference was found between groups in terms of demographics, initial severity or outcome or presumed cause of stroke. Mean time to CT scan was 125 min in migraine patients and 127 min in the control group. A no-mismatch pattern was equally found in migraine patients and controls, even after adjustment for age, sex and presence of proximal occlusion (p = .22). The final infarct volume was also similar in both groups.Migraine patients did not display more no-mismatch pattern than controls within the 4.5 h of stroke onset. This deviates from previous studies and may be due to our earlier time from stroke onset to CT scan. A history of migraine may lead to malignant progression of ischemia but occurring only after several hours.

Published
2020

4. Caffeine use during pregnancy: prevalence of use and newborn consequences in a cohort of French pregnant women

Author

Estelle Houivet, S. Lamy, Stéphane Marret, Florence Thibaut, Jacques Benichou, Martinez Rico, Clara, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Unité de biostatistiques [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Endothélium microcirculatoire cérébral et lésions du système nerveux central au cours du développement (Néovasc), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Psychiatrie-Addictologie [CHU Cochin - APHP] (Site Tarnier), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité)-Site Tarnier (hôpital Cochin) - APHP, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)-Site Tarnier (hôpital Cochin) - APHP

Subjects
[SDV]Life Sciences [q-bio], Birth characteristics, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Coffee, Cohort Studies, chemistry.chemical_compound, [SCCO]Cognitive science, 0302 clinical medicine, Pregnancy, Prevalence, Pharmacology (medical), [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Obstetrics, Confounding, General Medicine, 3. Good health, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, Prenatal Exposure Delayed Effects, Cohort, Female, France, Caffeine, Tea, medicine.medical_specialty, Energy drink, Cola (plant), 03 medical and health sciences, medicine, Humans, Adverse effect, Biological Psychiatry, Caffeine use, Fetus, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Infant, Newborn, [SCCO] Cognitive science, biology.organism_classification, medicine.disease, Newborn, 030227 psychiatry, chemistry, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Cola, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Many pregnant women, in the world, drink caffeine-containing beverages. Maternal caffeine consumption during pregnancy may have adverse effects on foetus but results are conflicting. Our goals were to estimate the prevalence of caffeine use in a cohort of French pregnant women using maternal self-reports and to evaluate the association between caffeine consumption during pregnancy and delivery and newborn characteristics. All pregnant women who gave birth in a large French urban area during a limited period of time were included (in total 724 mothers were included). Coffee, tea or cola consumption as well as pregnancy and neonate characteristics were analysed. The mean consumption of caffeine per day slightly decreased from the first to the third trimester of pregnancy: 587 caffeine users, with a consumption of caffeine of 59.2 ± 61.5 mg/day during the first trimester as compared to 577 consumers (54.3 ± 55.4 mg/day) during the third trimester, respectively. A significant decrease of neonates' birth length was observed when mothers were using at least 100 mg/day (or two cups) of caffeine during the second and third trimesters but this difference was no longer significant after adjustment on potential confounding factors such as tobacco use. The potential existence of other confounders (e.g. poorer dietary habits or other lifestyle variables) that might also be associated with reduced birth length, may not be excluded. Caffeine use during pregnancy was associated with reduced birth length but this effect was no longer significant after adjustment on potential confounding variables.

Published
2020

5. Autologous Myoblasts for the Treatment of Fecal Incontinence

Author

Olivier Boyer, Stéphanie Le Corre, Anne-Marie Leroi, Aurélie Bisson, Edith Koning, Jérémie Martinet, Francis Michot, Camille Giverne, Estelle Houivet, Jean-Jacques Tuech, Justine Déhayes, Valérie Bridoux, Jacques Benichou, Pascal Chambon, Serge Jacquot, and Dominique Bastit

Subjects
Adult, medicine.medical_specialty, Urology, Placebo-controlled study, Placebo, Injections, law.invention, Myoblasts, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, stem cells, law, medicine, Clinical endpoint, Humans, Fecal incontinence, Prospective Studies, Prospective cohort study, business.industry, Middle Aged, Randomized Controlled Trials, 3. Good health, Surgery, Clinical trial, fecal incontinence, Treatment Outcome, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Sphincter, Female, 030211 gastroenterology & hepatology, cell therapy, medicine.symptom, business, autologous myoblasts
Abstract

Objective: The aim of this study was to evaluate the efficacy of intrasphincteric injections of autologous myoblasts (AMs) in fecal incontinence (FI) in a controlled study. Summary of Background Data: Adult stem cell therapy is expected to definitively cure FI by regenerating damaged sphincter. Preclinical data and results of open-label trials suggest that myoblast therapy may represent a noninvasive treatment option. Methods: We conducted a phase 2 randomized, double-blind, placebo-controlled study of intrasphincteric injections of AM in 24 patients. The study compared outcome after AM (n = 12) or placebo (n = 12) injection using Cleveland Clinic Incontinence (CCI), score at 6 and 12 months. Patients in the placebo group were eligible to receive frozen AM after 1 year. Results: At 6 months, the median CCI score significantly decreased from baseline in both the AM (9 vs 15, P = 0.02) and placebo (10 vs 15, P = 0.01) groups. Hence, no significant difference was found between the 2 groups (primary endpoint) at 6 months. At 12 months, the median CCI score continued to ameliorate in the AM group (6.5 vs 15, P = 0.006), while effect was lost in the placebo group (14 vs 15, P = 0.35). Consequently, there was a higher response rate at 12 months in the treated than the placebo arm (58% vs 8%, P = 0.03). After delayed frozen AM injection in the placebo group, the response rate was 60% (6/10) at 12 months. Conclusions: Intrasphincteric AM injections in FI patients have shown tolerance, safety, and clinical benefit at 12 months despite a transient placebo effect at 6 months.

Published
2018

6. Hartmann's Procedure or Primary Anastomosis for Generalized Peritonitis due to Perforated Diverticulitis: A Prospective Multicenter Randomized Trial (DIVERTI)

Author

Lilian Schwarz, Estelle Houivet, Jean-Marc Regimbeau, Muriel Mathonnet, Igor Sielezneff, Charles Sabbagh, Jean-Jacques Tuech, François Mauvais, Mehdi Ouaissi, V. Bridoux, Diane Mege, Service de chirurgie digestive [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), CHU Amiens-Picardie, Hôpital de la Timone [CHU - APHM] (TIMONE), Homéostasie Cellulaire et Pathologies (HCP), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-CHU Limoges, Service de chirurgie digestive (Centre Hospitalier de Beauvais), Centre Hospitalier de Beauvais, Unité de biostatistiques [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Physiopathologie de l'Endothelium, Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Chirurgie digestive [CHU Amiens], Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Peritonitis, 030230 surgery, Anastomosis, law.invention, Stoma, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Colon, Sigmoid, law, Colostomy, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Medicine, Prospective Studies, Prospective cohort study, Diverticulitis, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Rupture, Spontaneous, business.industry, Mortality rate, Anastomosis, Surgical, Rectum, Surgical Stomas, Middle Aged, medicine.disease, 3. Good health, Surgery, 030220 oncology & carcinogenesis, Female, business
Abstract

Background About 25% of patients with acute diverticulitis require emergency intervention. Currently, most patients with diverticular peritonitis undergo a Hartmann's procedure. Our objective was to assess whether primary anastomosis (PA) with a diverting stoma results in lower mortality rates than Hartmann's procedure (HP) in patients with diverticular peritonitis. Study Design We conducted a multicenter randomized controlled trial conducted between June 2008 and May 2012: the DIVERTI (Primary vs Secondary Anastomosis for Hinchey Stage III-IV Diverticulitis) trial. Follow-up duration was up to 18 months. A random sample of 102 eligible participants with purulent or fecal diverticular peritonitis from tertiary care referral centers and associated centers in France were equally randomized to either a PA arm or to an HP arm. Data were analyzed on an intention-to-treat basis. The primary end point was mortality rate at 18 months. Secondary outcomes were postoperative complications, operative time, length of hospital stay, rate of definitive stoma, and morbidity. Results All 102 patients enrolled were comparable for age (p = 0.4453), sex (p = 0.2347), Hinchey stage III vs IV (p = 0.2347), and Mannheim Peritonitis Index (p = 0.0606). Overall mortality did not differ significantly between HP (7.7%) and PA (4%) (p = 0.4233). Morbidity for both resection and stoma reversal operations were comparable (39% in the HP arm vs 44% in the PA arm; p = 0.4233). At 18 months, 96% of PA patients and 65% of HP patients had a stoma reversal (p = 0.0001). Conclusions Although mortality was similar in both arms, the rate of stoma reversal was significantly higher in the PA arm. This trial provides additional evidence in favor of PA with diverting ileostomy over HP in patients with diverticular peritonitis. ClinicalTrials.gov Identifier: NCT 00692393.

Published
2017

7. Soluble vascular endothelial (VE) cadherin and autoantibodies to VE-cadherin in rheumatoid arthritis patients treated with etanercept or adalimumab

Author

Xavier Le-Loët, Christopher Banse, Estelle Houivet, Christian Marcelli, Barry Stidder, Helena Polena, Isabelle Vilgrain, Olivier Vittecoq, Peggy Philippe, Patrice Fardellone, Thierry Lequerré, Abir Khalil-Mgharbel, CHU Rouen, Normandie Université (NU), Laboratoire de développement et vieillissement de l'endothélium, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institute for Research and Innovation in Biomedicine (IRIB), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de rhumatologie [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Service de rhumatologie, CHU Amiens-Picardie, Service de Rhumatologie [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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF), and Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, 0301 basic medicine, Systemic disease, Soluble VE cadherin, Severity of Illness Index, Gastroenterology, Etanercept, Arthritis, Rheumatoid, Cohort Studies, 0302 clinical medicine, Longitudinal Studies, Prospective Studies, skin and connective tissue diseases, Middle Aged, Cadherins, Treatment Outcome, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Rheumatoid arthritis, Biomarker (medicine), Female, France, medicine.drug, Adult, musculoskeletal diseases, medicine.medical_specialty, Anti-vascular endothelial-cadherin antibody, Risk Assessment, 03 medical and health sciences, Rheumatology, Antigens, CD, Internal medicine, medicine, Adalimumab, Humans, Rheumatoid factor, Aged, Autoantibodies, 030203 arthritis & rheumatology, business.industry, Autoantibody, medicine.disease, 030104 developmental biology, Solubility, Immunology, Methotrexate, business, Biomarkers, Follow-Up Studies
Abstract

Objectives The aim of this study was to investigate the clinical value of sVE and anti-vascular endothelial-cadherin antibodies (AAVE) in RA treated with etanercept or adalimumab combined with methotrexate. Methods This was an 18-month prospective multicenter study in which patients had active RA, requiring TNF antagonist. sVE rates and AAVE titers were measured respectively by dot blot and ELISA. The relationship of these biomarkers with parameters reflecting articular or systemic disease activity, progression of structural damage, and response or remission to treatment was analyzed. Results Forty-eight patients received TNF blocking agents. Variation of sVE rates were significantly correlated with that of C-reactive protein (CRP) levels at weeks 6, 12, 26 and 52. A significant decrease in sVE levels was observed in the group of patients exhibiting a decrease in CRP levels as compared to the patient group with unmodified CRP. AAVE at baseline were correlated with rheumatoid factor. Kinetics analysis of sVE levels and AAVE titers showed that their level were not associated with disease activity score and to methotrexate/adalimumab or etanercept response. Conclusions sVE is a biomarker associated with systemic RA activity under anti-TNF. AAVE are related to autoantibodies usually associated to RA.

Published
2017

8. Sacral nerve modulation for faecal incontinence influence of age on outcomes and complications. A multicentre study

Author

Paul-Antoine Lehur, Guillaume Meurette, Diane Mege, Estelle Houivet, Vincent Wyart, Isabelle Etienney, Valérie Bridoux, Anne-Marie Leroi, Elsa Lambrescak, Jean-Luc Faucheron, Charlène Brochard, Henri Damon, François Mion, Igor Sielezneff, Laurent Siproudhis, Assistance Publique - Hôpitaux de Marseille (APHM), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Groupe Hospitalier Diaconesses Croix Saint-Simon, Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de chirurgie digestive [CHU Rouen], CHU Rouen, Normandie Université (NU), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Service de physiologie digestive, urinaire, respiratoire et de l'exercice [CHU Rouen], Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, and Jonchère, Laurent

Subjects
Adult, Male, medicine.medical_specialty, complications, faecal incontinence, Population, Lumbosacral Plexus, Surgical Revision, Electric Stimulation Therapy, elderly, 03 medical and health sciences, 0302 clinical medicine, sacral nerve modulation, Age groups, Medicine, Humans, In patient, Revision rate, education, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Aged, 80 and over, education.field_of_study, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, business.industry, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Gastroenterology, Age Factors, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Middle Aged, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Surgery, Electrodes, Implanted, age, 030220 oncology & carcinogenesis, Sacral nerve, outcome, 030211 gastroenterology & hepatology, Female, Implant, France, business, explantation, Fecal Incontinence
Abstract

AIM Faecal incontinence is frequent in the elderly. Little is currently known about the efficacy of sacral nerve modulation (SNM) in the elderly. The present study aimed to assess the impact of age on the outcome of SNM and on the surgical revision and explantation rates by comparing the results of a large data set of patients. METHOD Prospectively collected data from patients who underwent an implant procedure between January 2010 and December 2015 in seven French centres were retrospectively evaluated. In total, 352 patients [321 women; median age (range): 63 (24-86) years] were included. Clinically favourable and unfavourable outcomes, and surgical revision and explantation rates, were compared according to the age of the patients. RESULTS A similar outcome was observed when comparing patients

Published
2019

9. Risk factors associated to tobacco and alcohol use in a large French cohort of pregnant women

Author

Jacques Benichou, Stéphane Marret, Estelle Houivet, S. Lamy, Héloïse Delavenne, Delphine Allorge, Benjamin Hennart, Florence Thibaut, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), Team 4 'NeoVasc' - INSERM U1245, 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)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Lille, Impact de l'environnement chimique sur la santé humaine (IMPECS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Unité de Psychiatrie CHU C Nicolle, Normandie Université (NU)-Normandie Université (NU), Impact de l'environnement chimique sur la santé humaine - ULR 4483 (IMPECS), Centre de Psychiatrie et Neurosciences (U894), and Team 4 NeoVasc - Region Team ERI 28 INSERM (Neovasc)

Subjects
Adult, Meconium, medicine.medical_specialty, Alcohol Drinking, Pregnancy Trimester, Third, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Glucuronates, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, Neonatal Screening, 0302 clinical medicine, Pregnancy, Risk Factors, Surveys and Questionnaires, Environmental health, medicine, Humans, Prospective Studies, Cotinine, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, 030219 obstetrics & reproductive medicine, business.industry, Public health, Smoking, Infant, Newborn, Obstetrics and Gynecology, medicine.disease, 3. Good health, 030227 psychiatry, Pregnancy Complications, Psychiatry and Mental health, chemistry, Cohort, Smoking cessation, Marital status, Female, France, Pregnant Women, business
Abstract

Tobacco and/or alcohol use during pregnancy is a major public health concern. The aim of our study was to identify risk factors associated to maternal alcohol and tobacco use assessed by maternal self-reports combined with biological measurements in meconium samples of cotinine and ethylglucuronide which reflect fetal exposure to tobacco and alcohol, respectively, during the 3rd trimester of pregnancy. We conducted a prospective study in three maternity hospitals in a large urban area during consecutive weeks (2010 and 2011). Maternal sociodemographic and clinical characteristics were assessed after delivery, using the French version of the Addiction Severity Index. Cotinine and ethylglucuronide were measured in meconium samples. Seven hundred and twenty-four women were included, and 645 meconium samples collected. Using multivariate analyses, we found that not being married or having a smoking partner predicts maternal tobacco use. In contrast, a decreased risk was associated with higher education level and wanted pregnancy. The risk for alcohol use increased when the mother had been in conflict with any relative or her partner for a long time throughout her life, as well as in case of previous treatment for any mental or emotional disorder. Using multivariate analyses and cotinine presence in meconium samples, the risks were similar except for marital status, which was not associated to cotinine presence. Community education and prevention programs should urgently be improved for all women of childbearing age with a special focus on those with past histories of mental or emotional disorders and addictive disorders. Smoking cessation should be recommended to both parents.

Published
2019

10. Factors Associated With Short-term Relapse in Patients With Pemphigus Who Receive Rituximab as First-line Therapy

Author

Maria Polina Konstantinou, Sé Bastien Calbo, Vivien Hébert, Martine Avenel-Audran, Catherine Prost-Squarcioni, Pierre Vabres, Christophe Bedane, Michel D'Incan, Laurent Misery, C. Mignard, Marie Beylot-Barry, Estelle Houivet, Sophie Duvert-Lehembre, Bruno Sassolas, Marina Alexandre, Guillaume Chaby, Jean-David Bouaziz, Emmanuel Delaporte, Maud Maho-Vaillant, Olivier Dereure, Philippe Bernard, Denis Jullien, Pierre Balayé, Frédéric Caux, Marie-Aleth Richard, Jacques Benichou, Gaëlle Quéreux, Catherine Picard-Dahan, Nathalie Beneton, Bruno Labeille, Pascal Joly, Laurent Machet, Saskia Ingen-Housz-Oro, Sébastien Debarbieux, Alain Dupuy, Nicolas Dupin, and Marie-Laure Golinski

Subjects
Adult, Male, medicine.medical_specialty, Time Factors, Enzyme-Linked Immunosorbent Assay, Dermatology, Severity of Illness Index, law.invention, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, Randomized controlled trial, Predictive Value of Tests, Recurrence, Prednisone, law, Internal medicine, Positive predicative value, Post-hoc analysis, medicine, Humans, Immunologic Factors, Original Investigation, Aged, Autoantibodies, Desmoglein 3, business.industry, Middle Aged, medicine.disease, 3. Good health, Regimen, Pemphigus, 030220 oncology & carcinogenesis, Female, Rituximab, business, medicine.drug
Abstract

Importance Rituximab and short-term corticosteroid therapy are the criterion standard treatments for patients with newly diagnosed moderate to severe pemphigus. Objective To examine factors associated with short-term relapse in patients with pemphigus treated with rituximab. Design, Setting, and Participants This post hoc analysis of a randomized clinical trial (Comparison Between Rituximab Treatment and Oral Corticosteroid Treatment in Patients With Pemphigus [RITUX 3]) conducted from January 1, 2010, to December 31, 2015, included patients from 20 dermatology departments of tertiary care centers in France from the RITUX 3 trial and 3 newly diagnosed patients treated according to the trial protocol. Data analysis was performed from February 1 to June 30, 2019. Exposure Patients randomly assigned to the rituximab group in the RITUX 3 trial and the 3 additional patients were treated with 1000 mg of intravenous rituximab on days 0 and 14 and 500 mg at months 12 and 18 combined with a short-term prednisone regimen. Main Outcomes and Measures Baseline (pretreatment) clinical and biological characteristics (Pemphigus Disease Area Index [PDAI] score, ranging from 0-250 points, with higher values indicating more severe disease) and changes in anti–desmoglein (DSG) 1 and anti-DSG3 values as measured by enzyme-linked immunosorbent assay during the 3 months after rituximab treatment were compared between patients with disease relapse and those who maintained clinical remission during the first 12 months after treatment. The positive and negative predictive values of these factors were calculated. Results Among 47 patients (mean [SD] age, 54.3 [17.0] years; 17 [36%] male and 30 [64%] female) included in the study, the mean (SD) baseline PDAI score for patients with relapsing disease was higher than that of the patients with nonrelapsing disease (54 [33] vs 28 [24];P = .03). At month 3, 7 of 11 patients with relapsing disease (64%) vs 7 of 36 patients with nonrelapsing disease (19%) had persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher (P = .01). A PDAI score of 45 or higher defining severe pemphigus and/or persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher at month 3 provided a positive predictive value of 50% (95% CI, 27%-73%) and a negative predictive value of 94% (95% CI, 73%-100%) for the occurrence of relapse after rituximab. Conclusions and Relevance The findings suggest that initial PDAI score and changes in anti-DSG antibody values after the initial cycle of rituximab might help differentiate a subgroup of patients with high risk of relapse who might benefit from maintenance rituximab infusion at month 6 from a subgroup of patients with low risk of relapse who do not need early maintenance therapy. Trial Registration NCT00784589

Published
2020

11. Association of Intraventricular Hemorrhage and Death With Tocolytic Exposure in Preterm Infants

Author

Estelle Houivet, Pierre-Yves Ancel, Elsa Lorthe, Loïc Sentilhes, Gaëlle Pinto Cardoso, Laetitia Marchand-Martin, Stéphane Marret, Gilles Kayem, Hôpital Charles Nicolle [Rouen], 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), Endothélium microcirculatoire cérébral et lésions du système nerveux central au cours du développement (Néovasc), Normandie Université (NU)-Normandie Université (NU)-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)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Maternité Port-Royal [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Gynécologie-Obstétrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Université de Bordeaux (UB), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Sorbonne Universités, CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], and Gestionnaire, Hal Sorbonne Université

Subjects
Adult, Male, Tocolytic agent, medicine.medical_specialty, Population, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Pediatrics, 03 medical and health sciences, Vasotocin, 0302 clinical medicine, Pregnancy, medicine, Humans, 030212 general & internal medicine, education, Original Investigation, Cerebral Intraventricular Hemorrhage, education.field_of_study, 030219 obstetrics & reproductive medicine, business.industry, Obstetrics, Research, Infant, Newborn, Gestational age, Atosiban, General Medicine, medicine.disease, 3. Good health, Death, Pregnancy Complications, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Online Only, Tocolytic Agents, Intraventricular hemorrhage, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Relative risk, Tocolytic, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Infant, Premature, medicine.drug
Abstract

Key Points Question Is tocolysis associated with lower rates of death and intraventricular hemorrhage in preterm infants owing to an effect on the fetal blood-brain barrier? Findings In this cohort study of 1127 mothers who experienced preterm labor and delivered at gestational weeks 24 through 31, the estimated prevalence of death and/or grades III to IV intraventricular hemorrhage was significantly lower in preterm infants with vs without tocolytic exposure (25.3% vs 32.5%). Differences between atosiban and nifedipine exposure for death and/or intraventricular hemorrhage (44.9% vs 51.2%) and for intraventricular hemorrhage (39.1% vs 45.3%) were not significant. Meaning Results for tocolytics are reassuring regarding death and/or intraventricular hemorrhage in preterm infants, but other studies appear to be necessary to compare the effects of atosiban vs nifedipine., This population-based cohort study assesses the risks associated with tocolysis as measured by death and intraventricular hemorrhage in preterm infants and compares the risks between calcium channel blockers and atosiban., Importance No trials to date have demonstrated the benefits of tocolysis on death and/or neonatal morbidity in preterm infants; tocolytics may affect the fetal blood-brain barrier. Objectives To assess the risks associated with tocolysis in women delivering prematurely as measured by death and/or intraventricular hemorrhage (IVH) in preterm infants and to compare the association of calcium channel blockers (CCBs) nifedipine and nicardipine hydrochloride vs atosiban used for tocolysis with death and/or IVH. Design, Settings, and Participants The French 2011 EPIPAGE-2 (Enquête Épidémiologique sur les Petits Âges Gestationnels) cohort was limited to mothers admitted for preterm labor without fever, who delivered from 24 to 31 weeks of gestation from April 1 through December 31, 2011. Groups of preterm infants with vs without tocolytic exposure and groups with atosiban vs CCB exposure were compared. Data analysis was performed from June 7, 2014, through September 3, 2017. Exposures Tocolytics. Main Outcomes and Measures The primary outcome was a composite of death and/or IVH in preterm infants. Secondary outcomes included death, IVH, and a composite of death and/or grades III to IV IVH. Results A total of 1127 mothers (mean [SD] age, 25.5 [6.0] years) experienced preterm labor and gave birth to 1343 preterm infants with a male to female ratio of 1.23 and mean (SD) gestational age of 27 (2.5) weeks. Of these, 789 mothers (70.0%) received tocolytics; 314 (39.8%) received only atosiban, and 118 (15.0%) received only a CCB. In the first analysis, the primary outcome (death and/or IVH) was not significantly different in preterm infants with vs without tocolytic exposure (183 of 363 [50.4%] vs 207 of 363 [57.0%]; relative risk [RR], 0.88; 95% CI, 0.77-1.01; P = .07). The secondary outcome (death and/or grades III-IV IVH) was significantly lower in preterm infants with vs without tocolytic exposure (92 of 363 [25.3%] vs 118 of 363 [32.5%]; RR, 0.78; 95% CI, 0.62-0.98; P = .03). Other outcomes did not differ significantly. In the secondary analysis, death and/or IVH was not significantly different in preterm infants with atosiban vs CCB exposure (96 of 214 [44.9%] vs 62 of 121 [51.2%]; RR, 0.88; 95% CI, 0.70-1.10; P = .26), nor was IVH (77 of 197 [39.1%] vs 48 of 106 [45.3%]; RR, 0.86; 95% CI, 0.66-1.13; P = .29). Conclusions and Relevance In this population-based study, findings suggest that tocolytics were associated with a reduction of death and severe IVH. Other studies are necessary to compare perinatal outcomes after use of atosiban vs CCBs.

Published
2018

12. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial

Author

Catherine Prost-Squarcioni, Pierre Vabres, Philippe Bernard, Maud Maho-Vaillant, Estelle Houivet, Laurent Misery, Saskia Ingen-Housz-Oro, Sébastien Debarbieux, Alain Dupuy, Marie-Laure Golinski, P. Musette, Jean-David Bouaziz, Sophie Duvert-Lehembre, Pascal Joly, Laurent Machet, Nicolas Dupin, Denis Jullien, Frédéric Caux, Marie Beylot-Barry, Sébastien Calbo, Vivien Hébert, Martine Avenel-Audran, Bruno Sassolas, Carle Paul, Olivier Dereure, Gaëlle Quéreux, Emmanuel Delaporte, Jacques Benichou, Catherine Picard-Dahan, Nathalie Beneton, Bruno Labeille, Marie-Aleth Richard, Michel D'Incan, Christophe Bedane, Frédérique Caillot, Thomas Vermeulin, Marina Alexandre, Service de Dermatologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre de référence sur les maladies bulleuses autoimmunes (Rouen), CHU Rouen, Service de dermatologie [Paris], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de biostatistiques [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), University Hospital of St-Etienne, Department of Dermatology, Service de Dermatologie, Hôpital Bichat, AP-HP, Service de dermatologie (CHU de Toulouse), CHU Toulouse [Toulouse], Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Service de Dermatologie [AP-HP Hôpital Saint Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Service de dermatologie (CHU de Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Henri Mondor, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Equipe GAD (LNC - U1231), 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, Service de dermatologie (CHRU de Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Dermatologie [Rennes] = Dermatology [Rennes], CHU Pontchaillou [Rennes], Service de Dermatologie, Centre Hospitalier Sud, Hospices Civils, Lyon, Département de Dermatologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de Dermatologie et Oncologie Cutanée [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Dermatologie [CHU Limoges], CHU Limoges, Service de dermatologie [CH Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Service de dermatologie (Dermato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Dermatologie, Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de dermatologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Service d'informatique biomédicale [Rouen], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Unité de biostatistiques [Rouen], Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-AP-HP Hôpital Saint-Louis, Service de Dermatologie [Rennes], Service de dermatologie et oncologie cutanée (CHU Clermont Ferrand), CHRU Clermont Ferrand, Service de dermatologie (CH Le Mans), Hôpital Trousseau (Tours), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Centre Hospitalier Universitaire de Toulouse - CHU Toulouse (FRANCE), Centre de Recherches en Oncologie biologique et Oncopharmacologie ( CRO2 ), Aix Marseille Université ( AMU ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Diderot - Paris 7 ( UPD7 ) -AP-HP Hôpital Saint-Louis, Centre Hospitalier Universitaire de Reims ( CHU Reims ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), 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 ) -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 ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Université de Nantes ( UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre Hospitalier Universitaire d'Angers, CH Le Mans, Service de dermatologie ( Dermato - BREST ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Département de Médecine Interne et Pneumologie [Brest] ( DMIP - Brest ), Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Dermatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Service Dermatologie [CHU Toulouse], Pôle Clinique des Voies respiratoires [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and CHU Henri Mondor [Créteil]

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, Prednisolone, Follow-Up, Vulgaris, law.invention, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Prednisone, law, Internal medicine, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, Corticosteroids, Disease, Prospective Studies, Prospective cohort study, Adjuvant, Aged, business.industry, Standard treatment, General Medicine, Middle Aged, Mycophenolate-Mofetil, medicine.disease, 3. Good health, Surgery, Pemphigus, Regimen, 030104 developmental biology, Treatment Outcome, Combination, Rituximab, Female, Therapy, business, Single-Cycle, Intensity Score Absis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract

IF 44.002; International audience; Background High doses of corticosteroids are considered the standard treatment for pemphigus. Because long-term corticosteroid treatment can cause severe and even life-threatening side-effects in patients with this disease, we assessed whether first-line use of rituximab as adjuvant therapy could improve the proportion of patients achieving complete remission off-therapy, compared with corticosteroid treatment alone, while decreasing treatment side-effects of corticosteroids.Methods We did a prospective, multicentre, parallel-group, open-label, randomised trial in 25 dermatology hospital departments in France (Ritux 3). Eligible participants were patients with newly diagnosed pemphigus aged 18-80 years being treated for the first time (not at the time of a relapse). We randomly assigned participants (1: 1) to receive either oral prednisone alone, 1.0 or 1.5 mg/kg per day tapered over 12 or 18 months (prednisone alone group), or 1000 mg of intravenous rituximab on days 0 and 14, and 500 mg at months 12 and 18, combined with a short-term prednisone regimen, 0.5 or 1.0 mg/kg per day tapered over 3 or 6 months (rituximab plus short-term prednisone group). Follow-up was for 3 years (study visits were scheduled weekly during the first month of the study, then monthly until month 24, then an additional visit at month 36). Treatment was assigned through central computer-generated randomisation, with stratification according to disease-severity (severe or moderate, based on Harman's criteria). The primary endpoint was the proportion of patients who achieved complete remission off-therapy at month 24 (intention-to-treat analysis). This study is registered with ClinicalTrials.gov, number NCT00784589.Findings Between May 10, 2010, and Dec 7, 2012, we enrolled 91 patients and randomly assigned 90 to treatment (90 were analysed; 1 patient withdrew consent before the random assignment). At month 24, 41 (89%) of 46 patients assigned to rituximab plus short-term prednisone were in complete remission off-therapy versus 15 (34%) of 44 assigned to prednisone alone (absolute difference 55 percentage points, 95% CI 38.4-71.7; p

Published
2017

13. Clinical relevance of 8q23, 15q13 and 18q21 SNP genotyping to evaluate colorectal cancer risk

Author

Delphine Bonnet, Rosine Guimbaud, Pascaline Berthet, Anne-Françoise Cailleux, Marie-Pierre Buisine, Jacques Mauillon, Paul Gesta, David Malka, Stéphanie Baert-Desurmont, Estelle Cauchin, Estelle Houivet, Marine Lebrun, Caroline Abadie, Salima El Chehadeh, Isabelle Coupier, Lorena Ippolito, Julie Tinat, Philippe Jonveaux, Qing Wang, Marie Agnès Collonge-Rame, Françoise Desseigne, Sylvie Manouvrier, Jean-Christophe Saurin, Marion Gauthier-Villars, Jean-Marc Rey, Catherine Dugast, Laurence Brugières, Christine Toulas, Brigitte Bressac-de Paillerets, Pierre Laurent-Puig, Pascal Pujol, Sophie Giraud, Fabienne Prieur, Florence Polycarpe-Osaer, Jean Chiesa, Jacques Benichou, Dominique Leroux, Bruno Buecher, Ludovic Mansuy, Marie-Emmanuelle Morin-Meschin, Joanna Sokolowska, Marion Bougeard, Sophie Lejeune, Myriam Bronner, Jacqueline Duffour, Agnès Hardouin, Hakim Sebaoui, Valérie Bonadona, Julien Blot, Chrystelle Colas, Aziz Zaanan, Olivier Caron, Françoise Charbonnier, François Duhoux, Thierry Frebourg, Laurence Faivre, Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Cancéropole Nord-Ouest, 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), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Eugène Marquis (CRLCC), Oncologie thoracique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), CRLC Val d'Aurelle-Paul Lamarque, CRLCC Val d'Aurelle - Paul Lamarque, Centre Léon Bérard [Lyon], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de génétique médicale [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Service de Génétique Médicale [Lille], Institut de génétique médicale-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de génétique, Institut Curie Paris, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Service de génétique médicale CHU Grenoble Hôpital Couple Enfant, CHU Grenoble, Centre Hospitalier Georges Renon [Niort] (CH Georges Renon Niort), Institut Claudius Regaud, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Service de Génétique [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), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Génétique Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Génétique Clinique [CHRU Nïmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Onco-génétique, Service de génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service de génétique médicale [Toulouse], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service de génétique [Cliniques Universitaires Saint-Luc, Bruxelles], Cliniques Universitaires Saint-Luc [Bruxelles], Génétique biologique histologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Département de biologie et pathologie médicales [Gustave Roussy], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Service Génétique Médicale [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'Hépatologie et de Gastroentérologie [Lyon], Unité de recherche clinique [CHU Rouen], Normandie Université (NU)-Normandie Université (NU), and UL, NGERE

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Genotyping Techniques, [SDV]Life Sciences [q-bio], Single-nucleotide polymorphism, Bioinformatics, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Gene Frequency, Risk Factors, Internal medicine, Odds Ratio, Genetics, medicine, Humans, Genetic Predisposition to Disease, Prospective Studies, Prospective cohort study, Alleles, Genetics (clinical), Chromosomes, Human, Pair 15, business.industry, Case-control study, Odds ratio, Middle Aged, medicine.disease, Confidence interval, Lynch syndrome, 3. Good health, SNP genotyping, [SDV] Life Sciences [q-bio], 030104 developmental biology, Genetic Loci, Case-Control Studies, Female, Chromosomes, Human, Pair 18, Colorectal Neoplasms, business, Chromosomes, Human, Pair 8, Genome-Wide Association Study
Abstract

International audience; To determine if the at-risk single-nucleotide polymorphism (SNP) alleles for colorectal cancer (CRC) could contribute to clinical situations suggestive of an increased genetic risk for CRC, we performed a prospective national case-control study based on highly selected patients (CRC in two first-degree relatives, one before 61 years of age; or CRC diagnosed before 51 years of age; or multiple primary CRCs, the first before 61 years of age; exclusion of Lynch syndrome and polyposes) and controls without personal or familial history of CRC. SNPs were genotyped using SNaPshot, and statistical analyses were performed using Pearson's chi(2) test, Cochran-Armitage test of trend and logistic regression. We included 1029 patients and 350 controls. We confirmed the association of CRC risk with four SNPs, with odds ratio (OR) higher than previously reported: rs16892766 on 8q23.3 (OR: 1.88, 95% confidence interval (CI): 1.30-2.72; P=0.0007); rs4779584 on 15q13.3 (OR: 1.42, CI: 1.11-1.83; P=0.0061) and rs4939827 and rs58920878/Novel 1 on 18q21.1 (OR: 1.49, CI: 1.13-1.98; P=0.007 and OR: 1.49, CI: 1.14-1.95; P=0.0035). We found a significant (P

Published
2016

14. Evaluation of Lynch syndrome modifier genes in 748 MMR mutation carriers

Author

Olivier Caron, Estelle Houivet, Thierry Frebourg, Stéphanie Baert-Desurmont, Françoise Charbonnier, Jacques Benichou, Marie-Pierre Buisine, Solene Houlle, Julie Tinat, Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pharmacoepidemiologie et évaluation de l'impact des produits de santé sur les populations, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), LAboratoire de biologie moléculaire, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Peer, Hal, and Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie (UNIROUEN)

Subjects
Male, congenital, hereditary, and neonatal diseases and abnormalities, Letter, Population, Penetrance, Single-nucleotide polymorphism, Biology, DNA Mismatch Repair, 03 medical and health sciences, 0302 clinical medicine, Genetics, medicine, Humans, Genetic Predisposition to Disease, education, neoplasms, Genetics (clinical), MMR genes, 030304 developmental biology, 0303 health sciences, education.field_of_study, Genetic heterogeneity, Epistasis, Genetic, medicine.disease, Colorectal Neoplasms, Hereditary Nonpolyposis, digestive system diseases, Lynch syndrome, 3. Good health, MSH6, MSH2, 030220 oncology & carcinogenesis, Mutation, Modifier factors, Female, Allelic heterogeneity, France, Colorectal Neoplasms
Abstract

Several studies have reported that, in Lynch syndrome resulting from mutations of the mismatch repair (MMR) genes, a CA repeat ≤17 within the IGF1 promoter, SNPs within the xenobiotic metabolizing enzyme gene CYP1A1 and SNPs on 8q23.3 and 11q23.1 modify colorectal cancer (CRC) risk in MMR mutation carriers. We analysed the impact of these polymorphisms on CRC risk in 748 French MMR mutation carriers derived from 359 families. We also analysed the effect of the Novel 1 SNP (18q21), which has recently been shown to increase CRC risk in the general population. We observed a significant difference in the CRC-free survival time between males and females, between MSH2 and MSH6 mutation carriers and between MLH1 and MSH6, indicating that this series is representative of Lynch syndrome. In contrast, the univariate log-rank test, as well as multivariate Cox model analysis controlling for familial aggregation and mutated MMR gene, year of birth and gender showed that the polymorphic alleles tested were not associated with a significant CRC risk increase, neither on the entire sample nor among males and females. This discrepancy with previous reports might be explained both by the genetic heterogeneity between the different populations analysed and the allelic heterogeneity of the MMR mutations. We conclude that genotyping of these polymorphisms is not useful to evaluate CRC risk in MMR mutation carriers and to optimize their clinical follow-up.

Published
2011

15. Incidence and risk factors for striae gravidarum

Author

Jacques Benichou, D. Picard, Estelle Houivet, Bernard Thobois, Séverine Sellier, Pascal Joly, Patrick Fournet, Loïc Marpeau, Service de Dermatologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen], Unité de biostatistiques [CHU Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Service de Gynécologie-Obstétrique et Médecine de la Reproduction [CHU Caen], 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 dermatologie [Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)

Subjects
Adult, medicine.medical_specialty, Multivariate analysis, Esthetics, Cross-sectional study, [SDV]Life Sciences [q-bio], Dermatology, Weight Gain, Body Mass Index, Young Adult, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Risk Factors, Confidence Intervals, Odds Ratio, Prevalence, medicine, Humans, ComputingMilieux_MISCELLANEOUS, 030219 obstetrics & reproductive medicine, business.industry, Obstetrics, Incidence (epidemiology), Odds ratio, medicine.disease, Confidence interval, Cross-Sectional Studies, Logistic Models, Socioeconomic Factors, Multivariate Analysis, Female, France, medicine.symptom, Striae Distensae, business, Weight gain, Body mass index, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Maternal Age
Abstract

International audience

Published
2015

16. Increased prevalence of psoriasis in patients with coronary artery disease: results from a case-control study

Author

F. Dujardin, Estelle Houivet, R. Koning, C. Abasq, B. Veber, Damien Picard, Hélène Eltchaninoff, Cribier A, Jacques Benichou, C. Sin, and Pascal Joly

Subjects
Male, medicine.medical_specialty, Univariate analysis, business.industry, Incidence (epidemiology), Case-control study, Dermatology, Odds ratio, Coronary Artery Disease, medicine.disease, Surgery, Coronary artery disease, Risk Factors, Psoriasis, Internal medicine, Case-Control Studies, Medicine, Humans, Female, Prospective Studies, Risk factor, business, Prospective cohort study, Aged
Abstract

SummaryBackground The incidence of myocardial events has been reported to be increased in patients with psoriasis. Objectives To investigate whether psoriasis is an independent risk factor for coronary artery disease (CAD). Methods We compared the prevalence of psoriasis between case patients with a diagnosis of CAD based on coronary angiography findings and control patients with no CAD referred to the emergency surgery department for an acute noncardiovascular condition. Case and control patients were examined for the presence of psoriasis by two dermatologists. The prevalence of psoriasis was compared among patients with CAD according to CAD severity. Five-hundred cases and 500 age- and sex-matched controls were included. Results Using matched univariate analysis, the prevalence of psoriasis was about twofold higher in CAD case patients than in control patients [8·0% vs. 3·4%, odds ratio (OR) 2·64; 95% confidence interval (CI) 1·42–4·88]. Using unconditional multivariate analysis, the association of psoriasis with CAD appeared to be borderline significant (OR 1·84; 95% CI 0·99–3·40). Psoriasis in patients with CAD was significantly associated with three-vessel involvement relative to one-or two-vessel involvement (13·1% vs. 6·1%; OR 3·07; 95% CI 1·50–6·25). Conclusions The prevalence of psoriasis is twofold higher in patients with CAD than in control patients without CAD. It is associated with a more severe coronary artery involvement.

Published
2014

17. School-age outcomes following a randomized controlled trial of magnesium sulfate for neuroprotection of preterm infants

Author

Loïc Marpeau, Delphine Provost, Jacques Benichou, Estelle Houivet, Maya Enser, Stéphane Marret, and Clément Chollat

Subjects
Male, Pediatrics, medicine.medical_specialty, Adolescent, Infant, Premature, Diseases, Neuroprotection, Cerebral palsy, law.invention, Magnesium Sulfate, Randomized controlled trial, law, Pregnancy, Surveys and Questionnaires, medicine, Very Preterm Birth, Humans, Child, School age child, business.industry, Cerebral Palsy, fungi, Infant, Newborn, Cognition, Strengths and Difficulties Questionnaire, medicine.disease, Neuroprotective Agents, Treatment Outcome, Prenatal Exposure Delayed Effects, Pediatrics, Perinatology and Child Health, Female, business, Infant, Premature, Psychomotor Performance, Follow-Up Studies
Abstract

In a French randomized trial, children at school-age demonstrated no evidence of harm from fetal exposure to MgSO4 before very preterm birth. Motor dysfunction/death, qualitative behavioral disorders, cognitive difficulties, school grade repetition, and education services were decreased in the children exposed to MgSO4, although the differences were not significant.

Published
2013

18. Prognostic factors of paraneoplastic pemphigus

Author

Luc Thomas, Saskia Ingen-Housz-Oro, Sandy Léger, Gilles Chaumentin, Caroline Robert, Pierre-Jean Weiller, Philippe Courville, Fabienne Léonard, Pascal Joly, Laurent Machet, Stéphane Debarbieux, Estelle Houivet, M. Dandurand, Francis Carsuzaa, Jacqueline Chevrant-Breton, Jean-Philippe Arnault, François Aubin, Denis Jullien, Michel D'Incan, Gérard Guillet, Olivier Chosidow, Catherine Lok, Jean-Philippe Lacour, Vincent Ferranti, Danièle Gilbert, Damien Picard, Marie-Sylvie Doutre, I. Kupfer, Olivier Dereure, Jacques Benichou, Carle Paul, Béatrice Crickx, Emmanuel Delaporte, Jean-Michel Pignon, Ludovic Martin, Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Littoral, Environnement, Télédétection, Géomatique (LETG-Angers), Littoral, Environnement, Télédétection, Géomatique UMR 6554 (LETG), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université d'Angers (UA)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Brest (UBO)-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Géographie et d'Aménagement Régional de l'Université de Nantes (IGARUN), Université de Nantes (UN)-Université de Nantes (UN)-Université de Caen Normandie (UNICAEN), Université de Nantes (UN)-Université de Nantes (UN), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), 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), Service de Dermatologie, Hôtel-Dieu, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Department of Dermatology, Université d'Angers (UA), Service de dermatologie, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de Dermatologie, Centre Hospitalier Sud, Hospices Civils, Lyon, Protéines de défense des réponses immune et inflammatoire : identification, régulation et rôles physiopathologiques, Unité de biostatistiques [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire d'Etudes Environnementales des Systèmes Anthropisés, Université d'Angers ( UA ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Hospices Civils de Lyon ( HCL ), Institut Gustave Roussy ( IGR ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Unité de biostatistiques [Rouen], and CHU Rouen-Université de Rouen Normandie ( UNIROUEN )

Subjects
Male, Erythema, Paraneoplastic Syndromes, Kaplan-Meier Estimate, Severity of Illness Index, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 030207 dermatology & venereal diseases, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, Adrenal Cortex Hormones, Neoplasms, Erythema multiforme, Aged, 80 and over, Univariate analysis, integumentary system, Mortality rate, Castleman disease, Hazard ratio, General Medicine, Middle Aged, Prognosis, 3. Good health, 030220 oncology & carcinogenesis, Female, medicine.symptom, Rituximab, Immunosuppressive Agents, Adult, medicine.medical_specialty, Dystonin, [SDV.CAN]Life Sciences [q-bio]/Cancer, Nerve Tissue Proteins, Dermatology, 03 medical and health sciences, medicine, Humans, Immunologic Factors, Protein Precursors, Aged, Autoantibodies, Proportional Hazards Models, Retrospective Studies, Erythema Multiforme, Mucous Membrane, Proportional hazards model, business.industry, Plakins, Membrane Proteins, medicine.disease, Cytoskeletal Proteins, Paraneoplastic pemphigus, Desmoplakins, Multivariate Analysis, business, Carrier Proteins, Pemphigus
Abstract

International audience; OBJECTIVE To identify the prognostic factors of overall survival in a series of patients with paraneoplastic pemphigus (PNP). DESIGN Multicenter retrospective cohort study. SETTING Twenty-seven dermatology departments in France. PATIENTS A total of 53 patients (31 men and 22 women; median age, 59 years; age range, 30-88 years) were diagnosed as having PNP between 1992 and 2010. MAIN OUTCOME MEASURES Overall Kaplan-Meier survival rates were estimated, and features associated with survival were assessed using univariate (log-rank test) and multivariate (Cox regression) analyses. RESULTS The study included 53 patients with PNP. Thirty-six patients (68%) died during the study. The 1-, 3-, and 5-year overall survival rates were 49%, 41%, and 38%, respectively. The main causes of death were infections (n = 21) and evolution of neoplasia (n = 6). In univariate analysis, the main detrimental prognostic factors identified were erythema multiforme-like skin lesions (P = .05) and histologic keratinocyte necrosis (P = .03). None of the 5 patients with Castleman disease died during the study. After adjustment for age and sex in multivariate analysis, erythema multiforme-like skin lesions remained predictive of fatal outcome, with a 2-fold increase in death rate (hazard ratio [HR], 2.3; 95% CI, 1.05-5.03; P = .04). The prognosis of patients with PNP was even poorer when erythema multiforme-like skin lesions were associated with severe skin or mucosal involvement at presentation (HR of death, 3.0; 95% CI, 1.01-8.92; P = .049). CONCLUSION Patients with PNP with erythema multiforme-like skin lesions and histologic keratinocyte necrosis, especially when associated with extensive lesions at presentation, are likely to have a more severe and rapid fatal outcome and should be managed very carefully.

Published
2012

19. Decreased activity of soluble thrombomodulin and plasma procoagulant phospholipids in childhood bone marrow transplantation with severe complications

Author

Patrick Van Dreden, Aude Marie-Cardine, Jean-Pierre Vannier, Aurélie Rousseau, Marc Vasse, Pascale Schneider, and Estelle Houivet

Subjects
Blood Platelets, Male, Bone marrow transplantation, Endothelium, Adolescent, Thrombomodulin, Proinflammatory cytokine, medicine, Humans, Secretion, Favorable outcome, Child, Phospholipids, Bone Marrow Transplantation, business.industry, Hematology, Soluble thrombomodulin, Blood Coagulation Factors, medicine.anatomical_structure, Child, Preschool, Immunology, Allogeneic BMT, Female, business, Biomarkers
Abstract

Complications of bone marrow transplantation (BMT) are usually considered to be related to the secretion of inflammatory cytokines, which generate membrane microparticles rich in procoagulant phospholipids (PPL) from different cellular origins and release of endothelial proteins such as thrombomodulin (TM). The use of soluble TM quantified by ELISA (TM:Ag) as a marker of endothelial injury is complex in children since it is age-dependent.Using a functional assay which quantifies the activity of sTM activity (TMa), we performed a pilot study to analyze the ratio TMa/TM:Ag in a control group of 25 healthy children, 8 children with autologous and 16 children with allogeneic BMT. In this last group, 8 experienced BMT complications. In addition, we used a functional assay which quantifies PPL.In healthy children the ratio TMa/TM:Ag was independent of age and stable in children with a favorable outcome but significantly (p0.05) reduced by the use of antithymocyte globulin during the conditioning regimen, and regularly decreased in children with BMT complications. Surprisingly, low plasma PPL levels were associated with a poor outcome.The ratio TMa/TM:Ag could constitute a marker of endothelium injury, and its follow-up could be of interest for an early discrimination of children with high risk of complications during allogeneic BMT. The decrease of PPL could be also another marker of a poor evolution and deserves further investigations.

Published
2010

20. Enzyme-Linked Immunosorbent Assay for the Combination of Bullous Pemphigoid Antigens 1 and 2 in the Diagnosis of Bullous Pemphigoid

Author

Kossara Drenovska, Zely Arivelo Randriamanantany, Estelle Houivet, Jacques Benichou, Pascal Joly, A. Roussel, François Tron, and Danièle Gilbert

Subjects
Male, Epidermolysis bullosa acquisita, Pemphigoid, Dystonin, Enzyme-Linked Immunosorbent Assay, Nerve Tissue Proteins, Dermatology, Autoantigens, Sensitivity and Specificity, Antigen, Immunopathology, Pemphigoid, Bullous, medicine, Humans, Cicatricial pemphigoid, Fluorescent Antibody Technique, Indirect, Aged, Retrospective Studies, Aged, 80 and over, biology, business.industry, IIf, General Medicine, Non-Fibrillar Collagens, medicine.disease, Cytoskeletal Proteins, Immunology, biology.protein, Female, Bullous pemphigoid, Antibody, Carrier Proteins, business
Abstract

To assess the usefulness of enzyme-linked immunosorbent assay (ELISA) assessment of the combination of bullous pemphigoid antigen 1 (BPAG1) and BPAG2 in the diagnosis of bullous pemphigoid (BP).Retrospective study of serum samples from patients with BP.Tertiary care center.A total of 190 patients with newly diagnosed BP and 78 controls with other autoimmune bullous diseases.Serum samples were tested using commercialized BPAG1 and BPAG2 ELISA and indirect immunofluorescence (IIF).The sensitivity and specificity of ELISA for the combination of BPAG1 and BPAG2 in the diagnosis of BP were contrasted with ELISA for each of the antigens alone and with IIF.The sensitivity and specificity of ELISA for the combination of BPAG1 and BPAG2 were 87% and 88%, respectively, compared with 79% and 90% for BPAG2 ELISA, 61% and 96% for BPAG1 ELISA, and 81% and 63% for IIF. The combination of BPAG1 ELISA and BPAG2 ELISA permitted 8% and 16% gains in sensitivity compared with each of BPAG2 ELISA and BPAG1 ELISA alone, respectively. Anti-BPAG1 antibodies were detected in 15 of 40 BP serum samples with no anti-BPAG2 antibodies (38%) and in 8 of 13 serum samples from patients with BP and mucosal involvement (62%) compared with 2 of 22 samples of cicatricial pemphigoid (P = .002) and 0 of 16 epidermolysis bullosa acquisita serum samples (P.001). The BPAG2 ELISA values were more closely correlated with initial extent of BP lesions (r = 0.44, P.001) than BPAG1 ELISA values (r = 0.16, P = .03).Since the combination of BPAG1 and BPAG2 ELISA only slightly increases the sensitivity of BP diagnosis over BPAG2 ELISA alone, BPAG1 ELISA could be adequately proposed in a minority of BP cases with mucosal involvement and in those with no circulating anti-BPAG2 antibodies.

Published
2011

21. Meningococcal carriage during a clonal meningococcal B outbreak in France

Author

Gilles Berthelot, Muhamed-Kheir Taha, Ludovic Lemée, François Caron, Valérie Delbos, Jacques Benichou, Martin, Marie, CHU Rouen, Normandie Université (NU), Université de Rouen Normandie (UNIROUEN), Service des maladies infectieuses et tropicales [Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier de Dieppe, Institut Pasteur [Paris] (IP), The study was funded by the French Ministry of Health ('Programme Hospitalier de Recherche Clinique')., On behalf of the B14 STOP study group. Additional members of the B14 STOP study group: Steering committee: Jean-Michel Alonso (Institut Pasteur), Isabelle Parent du Châtelet (Institut de Veille Sanitaire), Martin Révillion (Cellule Interrégionale d’Epidémiologie de Haute-Normandie), Jean-Philippe Leroy (Centre Hospitalier Universitaire de Rouen), Jean-Philippe Rigaud (Centre Hospitalier Général de Dieppe). Coordination of the investigation center: Vincent Ferranti, Marion Duval-Affagard, and Michel Décreau (Centre Hospitalier Universitaire de Rouen). Microbiological analysis: Nathalie Gence, Christine Godey, and Danièle Verson (Centre Hospitalier Universitaire de Rouen), Ala-Eddine Deghmane, Eva Hong, and Corinne Ruckly (Institut Pasteur). Antibiotic consumption data collection: Marie-Noëlle Damon (Direction Régionale du Service Médical de Normandie). Statistical analysis: Estelle Houivet and Vanessa Grassi (Centre Hospitalier Universitaire de Rouen)., and Institut Pasteur [Paris]

Subjects
Male, MESH: Pharynx, Neisseria meningitidis, Serogroup B, medicine.disease_cause, MESH: Meningococcal Infections, Disease Outbreaks, 0302 clinical medicine, Medical microbiology, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, MESH: Child, Prevalence, 030212 general & internal medicine, MESH: Disease Outbreaks, Child, 0303 health sciences, education.field_of_study, Neisseria meningitidis, General Medicine, MESH: Infant, 3. Good health, Vaccination, Infectious Diseases, MESH: Young Adult, Child, Preschool, Chemoprophylaxis, Carrier State, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, Standardized rate, France, MESH: Carrier State, Microbiology (medical), Adult, medicine.medical_specialty, Adolescent, Population, 03 medical and health sciences, Young Adult, MESH: Cross-Sectional Studies, Internal medicine, MESH: Neisseria meningitidis, Serogroup B, medicine, Humans, education, MESH: Prevalence, MESH: Adolescent, MESH: Humans, 030306 microbiology, business.industry, MESH: Child, Preschool, Outbreak, Infant, MESH: Adult, Virology, MESH: Male, MESH: France, Meningococcal Infections, Carriage, Cross-Sectional Studies, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Pharynx, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female
Abstract

International audience; The aim of this study performed in Normandy, France, was to analyze the pharyngeal meningococcal carriage at the peak of a clonal meningococcal B outbreak, which was subsequently controlled using an outer membrane vesicle vaccination. This cross-sectional study included randomly selected subjects aged 1-25 years. Carriers and non carriers were compared using unconditional logistic regression. Among the 3,522 volunteers, there were 196 (standardized rate: 6.46 %) Neisseria meningitidis carriers, of which there were only five with the outbreak strain (B:14:P1.7,16/ST-32; standardized rate: 0.18 %). From the multivariate analysis, older age, smoking, higher degree of socialization, and social deprivation appear to favor the carriage of all the strains included. Prior antibiotic treatment up to 12 months before swabbing, even with β-lactam, was protective against carriage. Our data indicate a low overall meningococcal carriage rate with a surprising protective effect of prior antibiotic exposure. The observed low carriage rate of the epidemic strain (B:14:P1.7,16/ST-32) contrasts with the high incidence of invasive meningococcal diseases (IMD) due to this strain. Hence, our data underline the high virulence of the strain and suggest a low level of natural immunity of the population against this strain. Although highly resource-consuming, carriage studies are helpful in guiding the implementation of control measures of IMD, such as mass vaccination or chemoprophylaxis.

Published
2013

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