1,778 results on '"Vaillant"'
Search Results
2. Gait in Patients with Axial Spondyloarthritis: A Systematic Review of the Literature
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Jacques Vaillant, Julie Soulard, and Nicolas Vuillerme
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Ankylosing spondylitis ,medicine.medical_specialty ,Clinical tests ,business.industry ,Impaired gait ,medicine.disease ,Chronic inflammatory disease ,Physical medicine and rehabilitation ,Gait (human) ,Rheumatology ,Walk test ,Spondylarthritis ,Humans ,Medicine ,Spondylitis, Ankylosing ,In patient ,Axial spondyloarthritis ,business ,Gait ,human activities ,Axial Spondyloarthritis - Abstract
Axial spondyloarthritis (axSpA) is a chronic inflammatory disease predominantly affecting the axial skeleton. axSpA includes radiographic (i.e., ankylosing spondylitis (AS)) and non-radiographic forms (nr-axSpA). Although recent studies have reported that patients with AS have impaired gait, axSpA’s consequences on gait remain unknown. The present review’s objectives were to identify: 1) how gait is assessed in patients with axSpA, and 2) what the gait characteristics are of patients with axSpA. This systematic review’s protocol was registered in the Prospero database (CRD42020128509). Three databases were systematically searched using keywords related to axSpA and gait. Two independent reviewers selected the articles and extracted the data. The search revealed two hundred titles and abstracts, and two articles were finally included in this review, comprising a total of 132 patients with axSpA. One of the included studies used the 6 m maximum gait velocity test (axSpA: 2.2 ± 0.5 m/s), and the other used the six-minute walk test (axSpA: 414 ± 106 m). Neither study involved a control group to compare gait. Only two published studies assessed the gait performance of patients with axSpA using clinical tests. Furthermore, neither of them compared gait performance to healthy controls or differentiated gait between the AS and nr-axSpA forms of axSPA. The present literature review highlights the need for future research to learn more about how gait is impaired in different types of patients with axSpA.
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- 2022
3. French guidelines for the management of oral lichen planus (excluding pharmacological therapy)
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J. Rochefort, F. Le Pelletier, Vincent Sibaud, A.-S. Zlowodzki, S. Millot, Romain Lan, Mahtab Samimi, Céline Girard, Marie-Helene Tessier, Fabrice Campana, C. Leroux-Villet, Jean-Christophe Fricain, S. Mares, and Loïc Vaillant
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medicine.medical_specialty ,Pharmacological therapy ,medicine.diagnostic_test ,business.industry ,Dermatology ,Disease ,Hepatitis C ,medicine.disease ,Chronic inflammatory disease ,stomatognathic diseases ,Gingivitis ,Biopsy ,Oral and maxillofacial pathology ,Medicine ,Oral lichen planus ,medicine.symptom ,business - Abstract
Summary Introduction Oral lichen is a chronic inflammatory disease for which diagnostic management and follow-up are heterogeneous given the absence of specific guidelines in France. Our objective was to develop French multidisciplinary guidelines for the management of oral lichen. Materials and methods Working groups from the Groupe d’Etude de la Muqueuse Buccale (GEMUB) formulated a list of research questions and the corresponding recommendations according to the “formal consensus” method for developing practice guidelines. These recommendations were submitted to a group of experts and the degree of agreement for each recommendation was assessed by a scoring group. Results Twenty-two research questions, divided into 3 themes (nosological classification and initial assessment, induced oral lichenoid lesions, and follow-up) resulted in 22 recommendations. Initial biopsy for histology is recommended in the absence of reticulated lesions. Biopsy for direct immunofluorescence is recommended for ulcerated, erosive, bullous types and for diffuse erythematous gingivitis. Management should include a periodontal and dental check-up, and investigation for extra-oral lesions. Hepatitis C testing is recommended only if risk factors are present. Definitions, triggering factors and the management of “induced oral lichenoid lesions” were clarified. Oral lichen must be monitored by a practitioner familiar with the disease at least once a year, using objective tools. Conclusion This formalised consensus of multidisciplinary experts provides clinical practice guidelines on the management and monitoring of oral lichen.
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- 2022
4. Liver transplantation for iatrogenic bile duct injury during cholecystectomy: a French retrospective multicenter study
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Bertrand Suc, Laurence Chiche, Bruno Heyd, Philippe Bachellier, Stéphanie Truant, Jean-Philippe Adam, Olivier Soubrane, Christophe Laurent, Ephrem Salamé, René Adam, Maxime Guieu, Karim Boudjema, Jean-Christophe Vaillant, Francis Navarro, CHU Bordeaux [Bordeaux], CHU Strasbourg, CHU Toulouse [Toulouse], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), We declare we received no funding for this manuscript., Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
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medicine.medical_specialty ,Cirrhosis ,[SDV]Life Sciences [q-bio] ,medicine.medical_treatment ,Biliary cirrhosis ,Iatrogenic Disease ,030230 surgery ,Liver transplantation ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Medicine ,Cholecystectomy ,Retrospective Studies ,Hepatology ,business.industry ,Bile duct ,Mortality rate ,Gastroenterology ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Retrospective cohort study ,medicine.disease ,Liver Transplantation ,3. Good health ,Surgery ,Transplantation ,medicine.anatomical_structure ,Cholecystectomy, Laparoscopic ,030220 oncology & carcinogenesis ,Bile Ducts ,business - Abstract
The results of this study were presented during the 13th Congress of the E-AHPBA on June 3th 2019, in Amsterdam.; International audience; BACKGROUND: Major bile duct injuries (BDI) following cholecystectomy require complex reconstructive surgery. The aim was to collect the liver transplantations (LT) performed in France for major BDI following cholecystectomy, to analyze the risk factors and to report the results. METHODS: National multicenter observational retrospective study. All the patients who underwent a LT in France between 1994 and 2017, for BDI following cholecystectomy, were included. RESULTS: 30 patients were included. 25 BDI occurred in non hepato-biliary expert centers, 20 were initially treated in these centers. Median time between injury and LT was 3 years in case of an associated vascular injury (11 injuries), versus 11.7 years without vascular injury (p = 0.006). Post-transplant morbidity rate was 86.7%, mortality 23.5% at 5 years. CONCLUSION: Iatrogenic BDI remains a real concern with severe cases, associated with vascular damages or leading to cirrhosis, with no solution but LT. It is associated with high morbidity and not optimal results. This enlights the necessity of early referral of all major BDI in expert centers to prevent dramatic outcome. Decision to perform transplantation should be taken before dismal infectious situations or biliary cirrhosis and access to graft should be facilitated by Organ Sharing Organizations.
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- 2022
5. ESPEN guideline on hospital nutrition
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Stephan C. Bischoff, Elisabet Rothenberg, M. Vaillant, Ulla Siljamäki-Ojansuu, Elina Ioannou, Karen Ottens-Oussoren, Osman Abbasoglu, Laila Meija, Ronan Thibault, Diana Rubin, Claude Pichard, CHU Pontchaillou [Rennes], Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service d'endocrinologie diabétologie et nutrition [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Hôpital Anne-de-Bretagne, Faculty of Medicine [Hacettepe University], Hacettepe University = Hacettepe Üniversitesi, Limassol General Hospital, Riga Stradins University (RSU), VU University Medical Center [Amsterdam], Hôpitaux Universitaires de Genève (HUG), Kristianstad University College - HKR (SWEDEN), Tampere University Hospital, CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, University of Hohenheim, This guideline was solely financed by ESPEN, the European Society for Clinical Nutrition and Metabolism., Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Université de Rennes (UR)-CHU Pontchaillou [Rennes]-Hôpital Anne-de-Bretagne
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medicine.medical_specialty ,Monitoring ,[SDV]Life Sciences [q-bio] ,Acute care ,Clinical nutrition ,Critical Care and Intensive Care Medicine ,03 medical and health sciences ,Patient safety ,0302 clinical medicine ,Intolerances ,Food intake ,medicine ,030212 general & internal medicine ,Medical prescription ,ddc:616 ,2. Zero hunger ,Nutrition and Dietetics ,business.industry ,Malnutrition ,Guideline ,Diets ,medicine.disease ,Obesity ,3. Good health ,Family medicine ,030211 gastroenterology & hepatology ,business ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition - Abstract
International audience; In hospitals through Europe and worldwide, the practices regarding hospital diets are very heterogeneous. Hospital diets are rarely prescribed by physicians, and sometimes the choices of diets are based on arbitrary reasons. Often prescriptions are made independently from the evaluation of nutritional status, and without taking into account the nutritional status. Therapeutic diets (low salt, gluten-free, texture and consistency modified, …) are associated with decreased energy delivery (i.e. underfeeding) and increased risk of malnutrition. The European Society for Clinical Nutrition and Metabolism (ESPEN) proposes here evidence-based recommendations regarding the organization of food catering, the prescriptions and indications of diets, as well as monitoring of food intake at hospital, rehabilitation center, and nursing home, all of these by taking into account the patient perspectives. We propose a systematic approach to adapt the hospital food to the nutritional status and potential food allergy or intolerances. Particular conditions such as patients with dysphagia, older patients, gastrointestinal diseases, abdominal surgery, diabetes, and obesity, are discussed to guide the practitioner toward the best evidence based therapy. The terminology of the different useful diets is defined. The general objectives are to increase the awareness of physicians, dietitians, nurses, kitchen managers, and stakeholders towards the pivotal role of hospital food in hospital care, to contribute to patient safety within nutritional care, to improve coverage of nutritional needs by hospital food, and reduce the risk of malnutrition and its related complications.
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- 2021
6. Risk stratification in heart failure decompensation in the community: HEFESTOS score
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Jose-Maria Verdu-Rotellar, Radost Assenova, Liam G. Glynn, Heidrun Lingner, Miguel Angel Muñoz, Rosa Abellana, Peter Torsza, Djurdjica Lazic, Hans Thulesius, Helene Vaillant-Roussel, Jacopo Demurtas, and Lea Gril Jevsek
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Male ,medicine.medical_specialty ,Heart failure ,Insuficiència cardíaca ,Decompensation ,Logistic regression ,Risk Assessment ,Severity of Illness Index ,Ventricular Function, Left ,Health risk assessment ,Residence Characteristics ,Internal medicine ,medicine ,Diseases of the circulatory (Cardiovascular) system ,Humans ,Derivation ,Risk stratification ,Avaluació del risc per la salut ,Aged ,Aged, 80 and over ,Heart Failure ,Ejection fraction ,business.industry ,Incidence (epidemiology) ,Models, Cardiovascular ,Stroke Volume ,Odds ratio ,Original Articles ,medicine.disease ,Primary care ,Prognosis ,Europe ,Hospitalization ,RC666-701 ,Cohort ,Original Article ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Aims Because evidence regarding risk stratification predicting prognosis of patients with heart failure (HF) decompensation attended in primary care is lacking, we developed and externally validated a model to forecast death/hospitalization during the first 30 days after an episode of decompensation. The predictive model is based on variables easily obtained in primary care settings. Methods and results HEFESTOS is a multinational study consisting of a derivation cohort of HF patients recruited in 14 primary healthcare centres in Barcelona and a validation cohort from primary healthcare in 9 other European countries. The derivation and validation cohorts included 561 and 250 patients, respectively. Percentages of women in the derivation and validation cohorts were 56.3% and 47.6% (P = 0.026), respectively. Mean age was 82.2 years (SD 8.03) in the derivation cohort, and 79.3 years (SD 10.3) in the validation one (P = 0.001). HF with preserved ejection fraction represented 72.1% in the derivation cohort and 58.8% in the validation one (P = 0.004). Mortality/hospitalization during the first 30 days after a decompensation episode was 30.5% and 26% (P = 0.225) for the derivation and validation cohorts, respectively. Multivariable logistic regression models were performed to develop a score of risk. The identified predictors were worsening of dyspnoea [odds ratio (OR): 2.5; P = 0.001], orthopnoea (OR: 2.16; P = 0.01), paroxysmal nocturnal dyspnoea (OR: 2.25; P = 0.01), crackles (OR: 2.35; P = 0.01), New York Heart Association functional class III/IV (OR: 2.11; P = 0.001), oxygen saturation ≤ 90% (OR: 4.98; P 100 b.p.m. (OR: 2.72; P = 0.002), and previous hospitalization due to HF (OR: 2.45; P 20%. Outcome incidence was 2.7% for the low‐risk group, 12.8% for medium risk, and 46.2% for high risk in the derivation cohort, and 9.1%, 12.9%, and 39.6% in the validation one. Conclusions The HEFESTOS score, based on variables easily accessible in a community setting and validated in an external European cohort, properly predicted the risk of death/hospitalization during the first 30 days after an HF decompensation episode.
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- 2021
7. Recommandations du groupe d’étude de la muqueuse buccale pour la prise en charge du lichen oral
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F. Le Pelletier, Mahtab Samimi, C. Leroux-Villet, Marie-Helene Tessier, S. Mares, Romain Lan, Vincent Sibaud, Céline Girard, Fabrice Campana, A.-S. Zlowodzki, Loïc Vaillant, S. Millot, Jean-Christophe Fricain, and J. Rochefort
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business.industry ,Medicine ,Ocean Engineering ,Safety, Risk, Reliability and Quality ,business - Published
- 2021
8. Effet de la thérapie par bercement sur les troubles du comportement de la démence
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Olivier Guérin, Malek Zaafrane, Eléa Gaillard, Anne-Julie Vaillant-Ciszewicz, and Cyprien Arlaud
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medicine.medical_specialty ,business.industry ,Psychological intervention ,Nice ,Medicine ,General Medicine ,Behavioural disorders ,University hospital ,business ,Psychiatry ,computer ,Neurocognitive ,computer.programming_language - Abstract
Non-medicinal interventions (NMI) are recommended as a first-line treatment in gerontology in response to a behavioural disorder. The Thera Berce pilot study at the Nice University Hospital aims to determine whether the NMI corresponding to rocking in a comfort chair allows a reduction in disruptive behavioural disorders in people with neurocognitive disorders. Benefits and limitations.
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- 2021
9. Quality of evidence of the efficacy of therapeutic interventions on patient-important outcomes in Cochrane's systematic reviews’ abstracts: A survey
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Nemat Jaafari, Hélène Vaillant-Roussel, Benoit Tudrej, Denis Pouchain, Elodie Tawil, Caroline Huas, Rémy Boussageon, Christine Maynié-François, Florian Naudet, Collège Universitaire de Médecine Générale [Lyon] (CUMG), Université de Lyon, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Département de Médecine Générale, Université de Poitiers (DMG), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers-Université de Poitiers, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Fondation santé des Etudiants de France, Fondation Santé des Etudiants de France, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Tours (UT), AutomédiCation aCcompagnement Pluriprofessionnel PatienT (ACCePPT), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre de Recherches sur la Cognition et l'Apprentissage (CeRCA), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours, and Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Université de Poitiers
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Evidence-based medicine ,medicine.medical_specialty ,030309 nutrition & dietetics ,education ,Psychological intervention ,Placebo ,03 medical and health sciences ,0302 clinical medicine ,Intervention (counseling) ,parasitic diseases ,Clinical endpoint ,Medicine ,Pharmacology (medical) ,GRADE approach ,Intensive care medicine ,0303 health sciences ,Cochrane collaboration ,business.industry ,[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences ,030205 complementary & alternative medicine ,3. Good health ,Quality of evidence ,Patient-important outcome ,Systematic review ,business - Abstract
International audience; OBJECTIVE: The objective of this study was to evaluate the proportion of therapeutics that have proven their efficacy on patient-important outcomes with a high quality of evidence among Cochrane systematic reviews (SRs). METHODS: We surveyed a random sample of 400 SRs’ abstracts published between September 2012 and December 2015, which compared therapeutic interventions with at least a placebo or no intervention control. The primary endpoint was the proportion of SRs with a statistically significant efficacy on a patient-important outcome and with a high quality of evidence. RESULTS: Among the 400 abstracts surveyed, 32 (8%) found efficacy on a patient-important outcome with a high quality of evidence. Half of the 400 SRs (50.2%) evaluated a pharmacological intervention and 12% of these found efficacy of the intervention on a patient-important outcome with a reported high quality of evidence. CONCLUSION: Based on an analysis of 400 abstracts of SRs from the Cochrane Collaboration, we found that there is a low number of therapeutic interventions which have proven their efficacy on patient-important outcomes with a high quality of evidence.
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- 2021
10. Extended Spectrum Beta-Lactamase (ESBL) Produced by Gram-Negative Bacteria in Trinidad and Tobago
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Angel A. Justiz Vaillant, Patrick Eberechi Akpaka, Padman Jayaratne, and Clyde Wilson
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Microbiology (medical) ,medicine.medical_specialty ,Gram-negative bacteria ,biology ,business.industry ,Klebsiella pneumoniae ,medicine.medical_treatment ,Public health ,Review Article ,biology.organism_classification ,Microbiology ,QR1-502 ,High morbidity ,Antibiotic resistance ,Health care ,Global health ,Beta-lactamase ,medicine ,business - Abstract
Gram-negative bacterial infections are a global health problem. The production of beta-lactamase is still the most vital factor leading to beta-lactam resistance. In Trinidad and Tobago, extended spectrum beta-lactamase (ESBL) production has been detected and reported mainly in the isolates of Klebsiella pneumoniae and Escherichia coli and constitutes a public health emergency that causes high morbidity and mortality in some patients. In this literature review, the authors cover vast information on ESBL frequency and laboratory detection using both conventional and molecular methods from clinical data. The aim is to make the reader reflect on how the actual knowledge can be used for rapid detection and understanding of the spread of antimicrobial resistance problems stemming from ESBL production among common Gram-negative organisms in the health care system.
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- 2021
11. Response to systemic therapies in granulomatous cheilitis: Retrospective multicenter series of 61 patients
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Stéphane Nahon, Selma Azib-Meftah, Saskia Ingen-Housz-Oro, Frédéric Jaouen, Marie-Helene Tessier, Jean-Christophe Fricain, Didier Bessis, Vincent Sibaud, Marie Masson-Regnault, Nathalie Beneton, Amina Kaddour, Céline Girard, Loïc Vaillant, Laurent Misery, Emmanuel Delaporte, Mahtab Samimi, Université Francois Rabelais [Tours], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier]-Université de Montpellier (UM)
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Series (stratigraphy) ,medicine.medical_specialty ,business.industry ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,MEDLINE ,Medicine ,Dermatology ,business ,[SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology - Abstract
International audience
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- 2022
12. Pleural Effusion Occurring During Lung Cancer Immunotherapy: A Challenge for the Clinician
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Aurélien Brindel, Lucile Roussel, Gauthier Treffel, Yves Billon, Angelica Tiotiu, Celsio Pouget, and Pierre Vaillant
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Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Pleural effusion ,medicine.medical_treatment ,MEDLINE ,Immunotherapy ,medicine.disease ,Text mining ,Internal medicine ,Medicine ,business ,Lung cancer - Published
- 2022
13. Narrative Literature Review on Risk Factors Involved in Lung Cancers, Breast Cancers, Brain Cancers, Gastrointestinal Cancers, Gynecologic Cancers, and Urogenital Cancers
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Sehlule Vuma, Mark Seegobin, Makeisha Simon, Luke Ramsingh, Maryam Mohammed, Luke Maharaj, Angel A. Justiz Vaillant, Masud Niles, Matthew Surajbally, and Lyvan Gardiner
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Oncology ,medicine.medical_specialty ,Lung ,medicine.anatomical_structure ,business.industry ,Internal medicine ,General Engineering ,Urogenital Cancers ,Medicine ,business ,Malignancy ,medicine.disease ,Brain cancer - Abstract
In this study, we described the most critical risk factors for different malignancies including breast, prostate, lung, and colorectal carcinoma among others, with an emphasis on modifiable risk factors. We revised the literature review about risk factors involved in the genesis of cancer in various databases, including articles indexed in PUBMED, SCOPUS, PMC, and Google Scholar. Awareness of risk factors enables conscious decisions to be made in an effort to combat malignancies. Knowing risk factors is a mode of fighting malignancy. Diet, lifestyle, practises, and laboratory/clinical interventions were among risk factors of diverse malignancy. Diet, lifestyle, laboratory/clinical interventions all contribute to the genesis and prognosis in a variety of malignancies. We concluded that abstaining from risk factors can prevent the development of many malignancies in a century where this conundrum is raising disproportionately. By informing the public about modifiable risk factors cancer mortality rates can be reduced. It is treated here is to make the public aware of the modifiable risks of cancers.
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- 2021
14. Helicobacter pylori infection has a detrimental impact on the efficacy of cancer immunotherapies
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Erika Riva, Emeric Limagne, Marine M Leblond, Meriem Messaoudene, Brynn McMillan, Laurie Vaillant, Dominique Velin, Caroline Truntzer, Elisavet Machremi, Bertrand Routy, François Ghiringhelli, Gregory Verdeil, Paul Oster, Corentin Richard, and Christina Begka
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0301 basic medicine ,biology ,business.industry ,medicine.medical_treatment ,T cell ,Melanoma ,Gastroenterology ,Cancer ,Immunotherapy ,Helicobacter pylori ,medicine.disease ,biology.organism_classification ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Cancer immunotherapy ,030220 oncology & carcinogenesis ,Immunology ,medicine ,Lung cancer ,business ,CD8 - Abstract
ObjectiveIn this study, we determined whether Helicobacter pylori (H. pylori) infection dampens the efficacy of cancer immunotherapies.DesignUsing mouse models, we evaluated whether immune checkpoint inhibitors or vaccine-based immunotherapies are effective in reducing tumour volumes of H. pylori-infected mice. In humans, we evaluated the correlation between H. pylori seropositivity and the efficacy of the programmed cell death protein 1 (PD-1) blockade therapy in patients with non-small-cell lung cancer (NSCLC).ResultsIn mice engrafted with MC38 colon adenocarcinoma or B16-OVA melanoma cells, the tumour volumes of non-infected mice undergoing anticytotoxic T-lymphocyte-associated protein 4 and/or programmed death ligand 1 or anti-cancer vaccine treatments were significantly smaller than those of infected mice. We observed a decreased number and activation status of tumour-specific CD8+ T cells in the tumours of infected mice treated with cancer immunotherapies independent of the gut microbiome composition. Additionally, by performing an in vitro co-culture assay, we observed that dendritic cells of infected mice promote lower tumour-specific CD8+ T cell proliferation. We performed retrospective human clinical studies in two independent cohorts. In the Dijon cohort, H. pylori seropositivity was found to be associated with a decreased NSCLC patient survival on anti-PD-1 therapy. The survival median for H. pylori seropositive patients was 6.7 months compared with 15.4 months for seronegative patients (p=0.001). Additionally, in the Montreal cohort, H. pylori seropositivity was found to be associated with an apparent decrease of NSCLC patient progression-free survival on anti-PD-1 therapy.ConclusionOur study unveils for the first time that the stomach microbiota affects the response to cancer immunotherapies and that H. pylori serology would be a powerful tool to personalize cancer immunotherapy treatment.
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- 2021
15. Analysis of HBsAg Immunocomplexes and cccDNA Activity During and Persisting After NAP‐Based Therapy
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Michel Bazinet, Pavlina Jimbei, Valentina Smeşnoi, Liviu Iarovoi, Mark S. Anderson, Gavin Cloherty, Andrew Vaillant, Ulf Dittmer, Tatina Musteata, Iurie Moscalu, Jeff Gersch, Valentin Cebotarescu, Victor Pântea, Vera Holzmayer, Alina Jucov, Lilia Cojuhari, Mary C. Kuhns, and Gheorghe Plăcintă
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Adult ,Male ,Hepatitis B virus ,HBsAg ,Polymers ,Medizin ,RC799-869 ,Antiviral Agents ,Virus ,Hepatitis B, Chronic ,Antigen ,Pegylated interferon ,Nucleic Acids ,Humans ,Medicine ,Seroconversion ,Tenofovir ,Cross-Over Studies ,Hepatitis B Surface Antigens ,Hepatology ,business.industry ,virus diseases ,Alanine Transaminase ,Original Articles ,cccDNA ,Diseases of the digestive system. Gastroenterology ,Hepatitis B ,medicine.disease ,Hepatitis B Core Antigens ,Virology ,digestive system diseases ,Nap ,Treatment Outcome ,RNA, Viral ,Virus Inactivation ,Drug Therapy, Combination ,Female ,Original Article ,Interferons ,DNA, Circular ,business ,medicine.drug - Abstract
CA Extern Therapy with nucleic acid polymers (NAPs), tenofovir disoproxil fumarate (TDF), and pegylated interferon (pegIFN) achieve high rates of HBsAg loss/seroconversion and functional cure in chronic hepatitis B virus (HBV) infection. The role of hepatitis B surface antigen (HBsAg) seroconversion and inactivation of covalently closed circular DNA (cccDNA) in establishing functional cure were examined. Archived serum from the REP 401 study was analyzed using the Abbott ARCHITECT HBsAg NEXT assay (Chicago, IL), Abbott research use–only assays for HBsAg immune complexes (HBsAg ICs), circulating HBV RNA, and the Fujirebio assay for hepatitis B core-related antigen (HBcrAg; Malvern, PA). HBsAg became < 0.005 IU/mL in 23 participants during NAP exposure, which persisted in all participants with functional cure. HBsAg IC declined during lead-in TDF monotherapy and correlated with minor declines in HBsAg. Following the addition of NAPs and pegIFN, minor HBsAg IC increases (n = 13) or flares (n = 2) during therapy were not correlated with HBsAg decline, hepatitis B surface antibody (anti-HBs) titers, or alanine aminotransferase. HBsAg IC universally declined during follow-up in participants with virologic control or functional cure. Universal declines in HBV RNA and HBcrAg during TDF monotherapy continued with NAP + pegIFN regardless of therapeutic outcome. At the end of therapy, HBV RNA was undetectable in only 5 of 14 participants with functional cure but became undetectable after removal of therapy in all participants with functional cure. Undetectable HBV RNA at the end of therapy in 5 participants was followed by relapse to virologic control or viral rebound. Conclusion: Anti-HBs-independent mechanisms contribute to HBsAg clearance during NAP therapy. Inactivation of cccDNA does not predict functional cure following NAP-based therapy; however, functional cure is accompanied by persistent inactivation of cccDNA. Persistent HBsAg loss with functional cure may also reflect reduction/clearance of integrated HBV DNA. Clinicaltrials.org number NCT02565719.
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- 2021
16. What Role, if any, Should Economic Evaluation Play in Market Access Decisions of Pharmaceutical Treatments for Cancer Patients with Short Life Expectancy?
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Angel Justiz-Vaillant
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Expectancy theory ,Economic growth ,Economic evaluation ,medicine ,Market access ,Cancer ,Business ,medicine.disease ,Short life ,West indies - Abstract
Short Commentary By Angel Justiz-Vaillant, Department of Para-Clinical Sciences. University of the West Indies. St. Augustine Campus. Trinidad and Tobago
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- 2021
17. Gastric eosinophils are detrimental for Helicobacter pylori vaccine efficacy
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Brynn McMillan, Dominique Velin, Paul Oster, and Laurie Vaillant
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medicine.medical_treatment ,030231 tropical medicine ,Helicobacter Infections ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Gastric mucosa ,Animals ,Medicine ,030212 general & internal medicine ,Helicobacter pylori ,General Veterinary ,General Immunology and Microbiology ,biology ,business.industry ,Stomach ,Public Health, Environmental and Occupational Health ,Eosinophil ,Vaccine efficacy ,biology.organism_classification ,Eosinophils ,Vaccination ,Infectious Diseases ,medicine.anatomical_structure ,Gastric Mucosa ,Immunology ,biology.protein ,Molecular Medicine ,Antibody ,business ,Adjuvant - Abstract
Helicobacter pylori (Hp) colonizes the human gastric mucosa with a high worldwide prevalence. Currently, Hp can be eradicated by the use of antibiotics. Due to the increase of antibiotic resistance, new therapeutic strategies need to be devised: one such approach being prophylactic vaccination. Pre-clinical and clinical data showed that a urease-based vaccine is efficient in decreasing Hp infection through the mobilization of T helper (Th)-dependent immune effectors, including eosinophils. Preliminary data have shown that upon vaccination and subsequent Hp infection, eosinophils accumulate in the gastric mucosa, suggesting a possible implication of this granulocyte subset in the vaccine-induced reduction of Hp infection. In our study, we confirm that activated eosinophils, expressing CD63, CD40, MHCII and PD-L1 at their cell surface, infiltrate the gastric mucosa during vaccine-induced reduction of Hp infection. Strikingly, we provide evidence that bone marrow derived eosinophils efficiently kill Hp in vitro, suggesting that eosinophils may participate to the vaccine-induced reduction of Hp infection. However, conversely to our expectations, the absence of eosinophils does not decrease the efficacy of this Hp vaccine in vivo. Indeed, vaccinated mice that have been genetically ablated of the eosinophil lineage or that have received anti-Sialic acid-binding immunoglobulin-like lectin F eosinophil-depleting antibodies, display a lower Hp colonization when compared to their eosinophil sufficient counterparts. Although the vaccine induces similar urease-specific humoral and Th responses in both eosinophil sufficient and deficient mice, a decreased production of anti-inflammatory cytokines, such as IL-10, TGFβ, and calgranulin B, was specifically observed in eosinophil depleted mice. Taken together, our results suggest that gastric eosinophils maintain an anti-inflammatory environment, thus sustaining chronic Hp infection. Because eosinophils are one of the main immune effectors mobilized by Th2 responses, our study strongly suggests that the formulation of an Hp vaccine needs to include an adjuvant that preferentially primes Hp-specific Th1/Th17 responses.
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- 2021
18. Prévenir le VIH par la PrEP : enjeux et perspectives
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O. Guyonvarch, E. Rouveix, Virginie Supervie, Thierry Blanchon, T. Hanslik, and L. Vaillant
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medicine.medical_specialty ,030505 public health ,business.industry ,Gastroenterology ,Human immunodeficiency virus (HIV) ,Drug resistance ,medicine.disease_cause ,Clinical trial ,03 medical and health sciences ,Pre-exposure prophylaxis ,0302 clinical medicine ,Internal Medicine ,Medicine ,030212 general & internal medicine ,Hiv acquisition ,0305 other medical science ,business ,Intensive care medicine ,Sexual risk - Abstract
Pre-exposure prophlaxis (PrEP) is the use of antiretroviral drugs by uninfected people to prevent human immunodeficiency virus (HIV) infection. PrEP is used by people who are at substantial risk of being exposed to HIV. Numerous clinical trials have confirmed its effectiveness in reducing HIV acquisition and PrEP has been approved and allowed in several countries including France. However, PrEP uptake remains low as concerns about increase in sexual risk behaviour with PrEP use in the wake of a growing epidemic of sexually transmitted infections, and fear of drug resistance have been expressed. As a result, the difference between the proportion of people on PrEP and the proportion of people who would be very likely to use PrEP if they could access it -otherwise known as the PrEP gap- remains high. Nowadays, studies continue to explore long-term effects of PrEP as well as expand the array of available technologies and regimens.
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- 2021
19. A systematic review of the quality of conduct and reporting of survival analyses of tuberculosis outcomes in Africa
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Moses Ngari, Christopher Maronga, Michel Vaillant, Susanne Schmitz, and Lazarus K. Mramba
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Medicine (General) ,Tuberculosis ,Epidemiology ,030231 tropical medicine ,Health Informatics ,Context (language use) ,Kaplan-Meier Estimate ,03 medical and health sciences ,0302 clinical medicine ,R5-920 ,medicine ,Humans ,Time-to-event ,030212 general & internal medicine ,Survival analysis ,Estimation ,business.industry ,Regression analysis ,medicine.disease ,Report summary ,Survival function ,Sample size determination ,Sample Size ,Africa ,Systematic review ,business ,Research Article ,Demography - Abstract
Background Survival analyses methods (SAMs) are central to analysing time-to-event outcomes. Appropriate application and reporting of such methods are important to ensure correct interpretation of the data. In this study, we systematically review the application and reporting of SAMs in studies of tuberculosis (TB) patients in Africa. It is the first review to assess the application and reporting of SAMs in this context. Methods Systematic review of studies involving TB patients from Africa published between January 2010 and April 2020 in English language. Studies were eligible if they reported use of SAMs. Application and reporting of SAMs were evaluated based on seven author-defined criteria. Results Seventy-six studies were included with patient numbers ranging from 56 to 182,890. Forty-three (57%) studies involved a statistician/epidemiologist. The number of published papers per year applying SAMs increased from two in 2010 to 18 in 2019 (P = 0.004). Sample size estimation was not reported by 67 (88%) studies. A total of 22 (29%) studies did not report summary follow-up time. The survival function was commonly presented using Kaplan-Meier survival curves (n = 51, (67%) studies) and group comparisons were performed using log-rank tests (n = 44, (58%) studies). Sixty seven (91%), 3 (4.1%) and 4 (5.4%) studies reported Cox proportional hazard, competing risk and parametric survival regression models, respectively. A total of 37 (49%) studies had hierarchical clustering, of which 28 (76%) did not adjust for the clustering in the analysis. Reporting was adequate among 4.0, 1.3 and 6.6% studies for sample size estimation, plotting of survival curves and test of survival regression underlying assumptions, respectively. Forty-five (59%), 52 (68%) and 73 (96%) studies adequately reported comparison of survival curves, follow-up time and measures of effect, respectively. Conclusion The quality of reporting survival analyses remains inadequate despite its increasing application. Because similar reporting deficiencies may be common in other diseases in low- and middle-income countries, reporting guidelines, additional training, and more capacity building are needed along with more vigilance by reviewers and journal editors.
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- 2021
20. Progression of adenomyosis magnetic resonance imaging features under ulipristal acetate for symptomatic fibroids
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Antoine Netter, Pascale Siles, Julien Mancini, Anaïs Grob-Vaillant, Vincent Vidal, Aubert Agostini, Lisa Calderon, Hôpital de la Timone [CHU - APHM] (TIMONE), Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biostatistique et technologies de l'information et de la communication (BioSTIC) - [Hôpital de la Timone - APHM] (BiosTIC ), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), and GREFF, Stéphane
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Adult ,0301 basic medicine ,medicine.medical_specialty ,Norpregnadienes ,Pilot Projects ,Disease course ,03 medical and health sciences ,chemistry.chemical_compound ,Magnetic resonance imaging ,0302 clinical medicine ,Ulipristal acetate ,Contraceptive Agents, Female ,Humans ,Medicine ,Adenomyosis ,Prospective Studies ,Increased thickness ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,030219 obstetrics & reproductive medicine ,Pelvic MRI ,Leiomyoma ,medicine.diagnostic_test ,business.industry ,Obstetrics and Gynecology ,medicine.disease ,3. Good health ,030104 developmental biology ,Reproductive Medicine ,chemistry ,Disease Progression ,Female ,Thickening ,Radiology ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,After treatment ,MRI ,Developmental Biology - Abstract
International audience; Research question: What is the evolution of adenomyosis on magnetic resonance imaging (MRI) after a 3-month treatment course of daily 5 mg doses of ulipristal acetate (UPA) for symptomatic fibroids?Design: A monocentric prospective pilot study on patients who underwent a 3-month treatment course of UPA for symptomatic fibroids between January 2014 and December 2017. Patients underwent pelvic MRI shortly before (pre-MRI) and after treatment (post-MRI). The diagnosis of adenomyosis on MRI was defined by the observation of intramyometrial cysts and/or haemorrhagic foci within these cystic cavities and/or a thickening of the junctional zone >12 mm. The progression of adenomyosis was defined by the presence of at least one of the aforementioned criteria of adenomyosis on the pre-MRI and by at least one of the following on the post-MRI: (i) increased thickness of the junctional zone ≥20% and/or (ii) increased number of intramyometrial cysts. The appearance of adenomyosis was defined by the absence of the aforementioned criteria of adenomyosis on the pre-MRI and the presence of at least one of these criteria on the post-MRI.Results: Seventy-two patients were included. The MRI features of adenomyosis progressed for 12 of 15 patients (80.0%) for whom adenomyosis was identified on the pre-MRI. An appearance of adenomyosis was identified after treatment for 15 of 57 patients (26.3%) for whom adenomyosis was not identified on the pre-MRI.Conclusions: A 3-month treatment course of daily 5 mg doses of UPA could provoke a short-term progression or an emergence of typical adenomyosis intramyometrial cysts on MRI examinations.
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- 2021
21. Benefit of transaminase elevations in establishing functional cure of HBV infection during nap‐based combination therapy
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Liviu Iarovoi, Adalbert Krawczyk, Alina Jucov, Lilia Cojuhari, Ulf Dittmer, Valentin Cebotarescu, Iurie Moscalu, Victor Pântea, Pavlina Jimbei, Michel Bazinet, Andrew Vaillant, Valentina Smeşnoi, Gheorghe Plăcintă, and Tatiana Musteata
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Viral rebound ,Hepatitis B virus ,HBsAg ,medicine.medical_specialty ,Combination therapy ,Medizin ,Antiviral Agents ,Gastroenterology ,Transaminase ,03 medical and health sciences ,0302 clinical medicine ,Immunity ,Virology ,Internal medicine ,Humans ,Medicine ,030212 general & internal medicine ,Transaminases ,Retrospective Studies ,Hepatitis B Surface Antigens ,Hepatology ,business.industry ,virus diseases ,Alanine Transaminase ,digestive system diseases ,Nap ,Infectious Diseases ,DNA, Viral ,030211 gastroenterology & hepatology ,business - Abstract
Treatment of HBV infection with nucleic acid polymers and pegIFN is accompanied by transaminase elevations in 95% of participants. HBV viral rebound, partial cure (HBV DNA 2000 IU/mL, normal ALT) or functional cure (HBV DNA target not detected, HBsAgLLOQ, normal ALT) occurred in 27%, 38% and 35% of participants. Correlations between ALT, AST and GGT elevations, virologic baseline, response during therapy and HBV therapeutic outcome were investigated. A retrospective analysis of all 40 participants in the REP 401 study (NCT02565719) included maxima and area under the curve for ALT, AST and GGT, baseline virology, HBsAg and anti-HBs response and HBV therapeutic outcomes. ALT, AST and GGT elevations were asymptomatic, independent of baseline virologic status and anti-HBs response but correlated with HBsAg reduction ≥3 log
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- 2021
22. Adult human liver slice cultures: Modelling of liver fibrosis and evaluation of new anti-fibrotic drugs
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Olivier Scatton, Loriane Lair-Mehiri, Sylvie Lagaye, Jesintha Gaston, Jean-Christophe Vaillant, Vladimir A. Morozov, Pierre-Philippe Massault, Daria Kartasheva-Ebertz, Stanislas Pol, Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Robert Koch Institute [Berlin] (RKI), Immunobiologie des Cellules Dendritiques, The authors are deeply indebted to the patients for their essential contribution to the work. We would like to acknowledge the members of the Departments of Digestive Surgery (Groupe Hospitalier La Pitié Salpétrière and Groupe Hospitalier Cochin, Assistance Publique–Hôpitaux de Paris (AP-HP), Paris, France) and the Department of Hepatology (Groupe Hospitalier Cochin, AP-HP, Paris, France), Dr. Jérôme Guéchot (Hôpital Saint-Antoine, Pôle de Biologie Médicale et Pathologie, AP-HP, Paris, France), Dr. Phuong Nhi Bories (Groupe Hospitalier Cochin, Service de Biochimie, AP-HP, Paris, France), the staff of Genomic (GENOM’IC) and Histology (HISTIM) facilities (Cochin Institute, Paris, France) for valuable assistance. We are grateful to Dr. Matthew Albert for the critical reading of the manuscript. Dr. Daria M. Kartasheva-Ebertz received a Ph.D. fellowship from AP-HP, Paris, France., LAGAYE, SYLVIE, and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Nonalcoholic steatohepatitis ,Alcoholic liver disease ,Pathology ,medicine.medical_specialty ,Anti fibrotic ,Hepatitis C virus ,Liver fibrosis ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Medicine ,ComputingMilieux_MISCELLANEOUS ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Hepatology ,Human liver ,business.industry ,Drugs ,[SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy ,Human liver fibrosis ,Basic Study ,medicine.disease ,3. Good health ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,[SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy ,business ,Ex vivo model ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; BACKGROUNDLiver fibrosis can result in end-stage liver failure and death.AIMTo examine human liver fibrogenesis and anti-fibrotic therapies, we evaluated the three dimensional ex vivo liver slice (LS) model.METHODSFibrotic liver samples (F0 to F4 fibrosis stage according to the METAVIR score) were collected from patients after liver resection. Human liver slices (HLS) were cultivated for up to 21 days. Hepatitis C virus (HCV) infection, alcohol (ethanol stimulation) and steatosis (palmitate stimulation) were examined in fibrotic (F2 to F4) liver slices infected (or not) with HCV. F0-F1 HLS were used as controls. At day 0, either ursodeoxycholic acid (choleretic and hepatoprotective properties) and/or α-tocopherol (antioxidant properties) were added to standard of care on HLS and fibrotic liver slices, infected (or not) with HCV. Expression of the biomarkers of fibrosis and the triglyceride production were checked by quantitative reverse transcription polymerase chain reaction and/or enzyme-linked immunosorbent assay.RESULTSThe cultures were viable in vitro for 21 days allowing to study fibrosis inducers and to estimate the effect of anti-fibrotic drugs. Expression of the biomarkers of fibrosis and the progression to steatosis (estimated by triglycerides production) was increased with the addition of HCV and /or ethanol or palmitate. From day 15 of the follow-up studies, a significant decrease of both transforming growth factor β-1 and Procol1A1 expression and triglycerides production was observed when a combined anti-fibrotic treatment was applied on HCV infected F2-F4 LS cultures.CONCLUSIONThese results show that the human three dimensional ex vivo model effectively reflects the in vivo processes in damaged human liver (viral, alcoholic, nonalcoholic steatohepatitis liver diseases) and provides the proof of concept that the LS examined model permits a rapid evaluation of new anti-fibrotic therapies when used alone or in combination
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- 2021
23. Gastric Band Slippage: Beware of the Refeeding Syndrome After the Band Removal—Comment on 'Should We Introduce a Gastric Band Removal Schedule?'
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Margot Denis, Adriana Torcivia, Laurent Genser, Jean-Christophe Vaillant, Clemence Boutron, and Sylvie Breton
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medicine.medical_specialty ,Schedule ,Nutrition and Dietetics ,Gastroplasty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Bariatric Surgery ,Band removal ,Prostheses and Implants ,Refeeding syndrome ,medicine.disease ,Obesity, Morbid ,Surgery ,Gastric band ,medicine ,Humans ,Refeeding Syndrome ,Slippage ,business - Published
- 2021
24. Controlling healthcare-associated transmission of SARS-CoV-2 variant of concern 202012/01 in a large hospital network
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C. Duverger, V. Souyri, C. Monteil, S. Fournier, F. Espinasse, M.C. Gramer, M. Lepainteur, D. Seytre, J.R. Zahar, S. Nerome, C. Ciotti, I. Garrigues, M.L. Delaby, N. Fortineau, S. Ouzani, M. Kecharem, J.C. Lucet, S. Kernéis, S. Géra, G. Bendjelloul, L. Vaillant, M. Vanderbrugghe, V. Goldstein, C. Loison, S. Borde, V. Moulin, C. Leboydre, V. Derouin, A. Casetta, L. Meyer, A. Akpabie, N. Kassis-Chikhani, A. Maurand, M. Silvie, J.W. Decousser, F. Fourreau, B. Hacquin, A. Tackin, A. Lomont, N. Sabourin, R. Amarsy, S. Roulleau, Y. Boufflers, N. Idri, P. Frange, P. Baune, J. Robert, N. Osinski, C. Tamames, J. Auraix, N. Forest, E. Pierson, C. Lawrence, C. Flament, G. Rolland, P. Mariani, K. Belhacel, B. Salauze, F. Barbut, S. Jolivet, N. Audrain, I. Simon, L. Turpin, M. Rouveau, M.T. Le Cam, C. Eble, W. Zebiche, V. Simha, C. Grudzien, M. Denis, E. Le-Roux, S. Angerand, and C. Charpinet
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Microbiology (medical) ,Healthcare associated infections ,Hospital network ,cross-transmission ,2019-20 coronavirus outbreak ,SARS-CoV-2 ,Transmission (medicine) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,COVID-19 ,Outbreak ,General Medicine ,infection control ,Virology ,Hospitals ,Infectious Diseases ,healthcare-associated infections ,Healthcare associated ,outbreaks ,Humans ,Infection control ,Medicine ,business ,Letter to the Editor ,Delivery of Health Care - Published
- 2021
25. Feeding Eggs from Hens Immunized with Specific KLH-Conjugated HIV Peptide Candidate Vaccines to Chicks Induces Specific Anti-HIV gp120 and gp41 Antibodies that Neutralize the Original HIV Antigens
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Oliver Pérez, Fisher Smikle, Ferrer Cosme, and Justiz Vaillant
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chemistry.chemical_classification ,Anti hiv ,Reverse vaccinology ,Human immunodeficiency virus (HIV) ,Peptide ,Biology ,Conjugated system ,Gp41 ,medicine.disease_cause ,Virology ,HIV Antigens ,chemistry ,biology.protein ,medicine ,Antibody - Published
- 2020
26. International validation of the Bullous Pemphigoid Disease Area Index severity score and calculation of cut‐off values for defining mild, moderate and severe types of bullous pemphigoid*
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Pascal Joly, Catherine Prost-Squarcioni, Aikaterini Patsatsi, Dimitra Kiritsi, Snejina Vassileva, Patrice Plantin, L. Friedrichsen, Fabienne Jouen, W. Masmoudi, A. Zebrowska, S. Hofmann, V Ferranti, N. Litrowski, Gaëlle Quéreux, Vivien Hébert, D. Kottler, Sophie Duvert-Lehembre, M. Vaillant, C. Abasq, and C. Moltrasio
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Pemphigoid ,medicine.medical_specialty ,Percentile ,Dystonin ,Intraclass correlation ,Enzyme-Linked Immunosorbent Assay ,Dermatology ,Autoantigens ,Severity of Illness Index ,Gastroenterology ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Interquartile range ,Internal medicine ,Pemphigoid, Bullous ,Severity of illness ,medicine ,Humans ,Autoantibodies ,business.industry ,Reproducibility of Results ,Non-Fibrillar Collagens ,medicine.disease ,Europe ,Quartile ,Cut-off ,Bullous pemphigoid ,business - Abstract
BACKGROUND The Bullous Pemphigoid Disease Area Index (BPDAI) score has been proposed to provide an objective measure of bullous pemphigoid (BP) activity. OBJECTIVES The objective of this study was to calculate BPDAI cut-off values defining mild, moderate and severe BP. We also aimed to assess the interrater reliability and correlation with the number of daily new blisters, and anti-BP180 and anti-BP230 antibodies. METHODS Severity scores were recorded by two blinded investigators. Anti-BP180 and anti-BP230 antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Cut-off values defining mild, moderate and severe subgroups were calculated based on the 25th and 75th percentiles of the BPDAI score. RESULTS In total, 285 patients with BP were enrolled from 50 dermatology departments in Europe. Median BPDAI activity was 37·5 points (range 0-164). Cut-off values corresponding to the first and third quartiles of the BPDAI score were 20 and 57, respectively; thus, these values were used to define mild (≤ 19), moderate (≥ 20 and ≤ 56) and severe (≥ 57) BP. The median BPDAI score for patients with ≤ 10 daily new blisters was 26 [interquartile range (IQR) 17-45], and for patients with > 10 daily new blisters the median score was 55 (IQR 39-82). The BPDAI intraclass correlation coefficient measured at baseline was 0·97 and remained higher than 0·90 up to month 6. The improvement in the BPDAI score was correlated with the absolute decrease in anti-BP180 ELISA value (Spearman's rank r = 0·34, P
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- 2020
27. Overlap and Mutual Distinctions Between Clinical Recovery and Personal Recovery in People With Schizophrenia in a One-Year Study
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Dubreucq, Julien, Gabayet, Franck, Godin, Ophélia, Andre, Myrtille, Aouizerate, Bruno, Capdevielle, Delphine, Chereau, Isabelle, Clauss-Kobayashi, Julie, Coulon, Nathalie, D’amato, Thierry, Dorey, Jean-Michel, Dubertret, Caroline, Faraldo, Mégane, Laouamri, Hakim, Leigner, Sylvain, Lancon, Christophe, Leboyer, Marion, Llorca, Pierre-Michel, Mallet, Jasmina, Misdrahi, David, Passerieux, Christine, Rey, Romain, Pignon, Baptiste, Schorr, Benoit, Urbach, Mathieu, Schürhoff, Franck, Szoke, Andrei, Berna, Fabrice, Haffen, E, Barteau, V, Bensalem, S, Souryis, K, Petrucci, J, Wahiche, G, Bourguignon, E, Deloge, A, Vilà, E, Blanc, O, Denizot, H, Honciuc, R, Lacelle, D, Pires, S, Portalier, C, Leignier, S, Roman, C, Chesnoy-Servanin, G, Vehier, A, Faget, C, Metairie, E, Peri, P, Vaillant, F, Boyer, L, Fond, Guillaume, Vidailhet, P, Zinetti-Bertschy, A, Michel, T, Garbisson, A, Belmonte, C, Dubois, T, Esselin, S, Jarroir, M, Fondation FondaMental [Créteil], Centre Hospitalier Alpes Isère, IMRB - 'Biologie du système neuromusculaire' [Créteil] (U955 Inserm - UPEC), École nationale vétérinaire - Alfort (ENVA)-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Charles Perrens, Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Clermont Auvergne (UCA), Les Hôpitaux Universitaires de Strasbourg (HUS), Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie (NCPS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier le Vinatier [Bron], Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Pôle de psychiatrie et d'addictologie des Hôpitaux Universitaires Henri-Mondor [Créteil], Centre hospitalier universitaire Henri-Mondor [Créteil], Centre Hospitalier de Versailles André Mignot (CHV), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg-Université de Strasbourg (UNISTRA), Centre de recherche en neurosciences de Lyon (CRNL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre hospitalier Charles Perrens [Bordeaux], Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
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Adult ,Male ,medicine.medical_specialty ,[SDV]Life Sciences [q-bio] ,Meaningful life ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,Full recovery ,personal recovery ,Medicine ,Humans ,psychosocial treatment ,030212 general & internal medicine ,full recovery ,Depression (differential diagnoses) ,Analysis of Variance ,Chi-Square Distribution ,business.industry ,Perspective (graphical) ,Recovery of Function ,Mental illness ,medicine.disease ,clinical recovery ,030227 psychiatry ,schizophrenia ,Psychiatry and Mental health ,Schizophrenia ,Quality of Life ,Female ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,business ,Psychosocial ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Regular Articles - Abstract
Recovery is a multidimensional construct that can be defined either from a clinical perspective or from a consumer-focused one, as a self-broadening process aimed at living a meaningful life beyond mental illness. We aimed to longitudinally examine the overlap and mutual distinctions between clinical and personal recovery. Of 1239 people with schizophrenia consecutively recruited from the FondaMental Advanced Centers of Expertise for SZ network, the 507 present at one-year did not differ from those lost to follow-up. Clinical recovery was defined as the combination of clinical remission and functional remission. Personal recovery was defined as being in the rebuilding or in the growth stage of the Stages of Recovery Instrument (STORI). Full recovery was defined as the combination of clinical recovery and personal recovery. First, we examined the factors at baseline associated with each aspect of recovery. Then, we conducted multivariable models on the correlates of stable clinical recovery, stable personal recovery, and stable full recovery after one year. At baseline, clinical recovery and personal recovery were characterized by distinct patterns of outcome (i.e. better objective outcomes but no difference in subjective outcomes for clinical recovery, the opposite pattern for personal recovery, and better overall outcomes for full recovery). We found that clinical recovery and personal recovery predicted each other over time (baseline personal recovery for stable clinical recovery at one year; P = .026, OR = 4.94 [1.30–23.0]; baseline clinical recovery for stable personal recovery at one year; P = .016, OR = 3.64 [1.31–11.2]). In short, given the interaction but also the degree of difference between clinical recovery and personal recovery, psychosocial treatment should target, beyond clinical recovery, subjective aspects such as personal recovery and depression to reach full recovery.
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- 2022
28. The ANTENATAL multicentre study to predict postnatal renal outcome in fetuses with posterior urethral valves: objectives and design
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Buffin-Meyer, Bénédicte, Klein, Julie, van der Zanden, Loes F M, Levtchenko, Elena, Moulos, Panogiotis, Lounis, Nadia, Conte-Auriol, Françoise, Hindryckx, An, Wühl, Elke, Persico, Nicola, Oepkes, Dick, Schreuder, Michiel F, Tkaczyk, Marcin, Ariceta, Gema, Fossum, Magdalena, Parvex, Paloma, Feitz, Wout, Olsen, Henning, Montini, Giovanni, Decramer, Stéphane, Schanstra, Joost P, De Catte, Luc, Vayssieres, Christophe, Sartor, Agnès, Groussolles, Marion, Plard, Christelle, Guerby, Paul, Connan, Laure, Morin, Mathieu, Simon, Elizabeth, Breaud, Jean, Saliou, Anne-Hélène, De Parscau, Loic, Jay, Nadine, Germouty, Isabelle, Le Bouar, Gwenaelle, Ryckewaert, Amelie, Manca-Pellissier, Marie-Christine, Merrot, Thierry, Laurichesse, Helene, Gallot, Denis, Bessenay, Lucie, Bidat, Laurent, Boize, Philippe, Winer, Norbert, Allain-Launey, Emma, Le Vaillant, Claudine, Prieur, Fabienne, Lavocat, Marie-Pierre, Coatleven, Frederic, Debromez, Eric, Harembat, Jérôme, Llanas, Brigitte, Favre, Romain, Moog, Raphael, Zaloszyc, Ariane, Massardier, Jérôme, Demede, Delphine, Perrotin, Franck, Cloarec, Sylvie, Vequeau-Goua, Valérie, Descombes, Emmanuelle, Boulot, Pierre, Morin, Denis, Fuchs, Florent, Tenenbaum, Julie, Ville, Yves, Blanc, Thomas, Heidet, Laurence, Paris, Anne, Dobremez, Eric, Froute, Marie-Françoise, Gondry, Jean, Muszynski, Charles, Haraux, Elodie, Lobelle, Fabienne, Chevreau, Julien, Rosenblatt, Jonathan, Baudoin, Véronique, Deschenes, Georges, Guigue, Virginie, Amblard, Florence, Bourdat-Michel, Guylhène, Schaefer, Franz, Elsässer, Michael, Rossi, Federica, Manzoni, Gianantonio, De Marco, Erika A, Capone, Valentina, Caforio, Leonardo, Zaccara, Antonio, Innocenzi, Michele, Bagolan, Pietro, Capozza, Nicola, Castagnetti, Marco, Mancini, Mariangela, van Scheltema, Phebe Adama, Kortmann, Barbara, Schreuder, Michiel, Stańczyk, Małgorzata, Szaflik, Krzysztof, Wojtera, Justyna, Krzeszowski, Waldemar, Talar, Tomasz, Pawłowska, Barbara, Fortecka-Piestrzeniewicz, Katarzyna, Olejniczak, Dariusz, Arevalo, Silvia, Rodo, Carlota, Lindgren, Peter, Chehade, Hassib, ANTENATAL Consortium, Hindryckx, A., De Catte, L., Vayssieres, C., Sartor, A., Groussolles, M., Plard, C., Guerby, P., Connan, L., Morin, M., Simon, E., Breaud, J., Saliou, A.H., De Parscau, L., Jay, N., Germouty, I., Le Bouar, G., Ryckewaert, A., Manca-Pellissier, M.C., Merrot, T., Laurichesse, H., Gallot, D., Bessenay, L., Bidat, L., Boize, P., Winer, N., Allain-Launey, E., Le Vaillant, C., Prieur, F., Lavocat, M.P., Coatleven, F., Debromez, E., Harembat, J., Llanas, B., Favre, R., Moog, R., Zaloszyc, A., Massardier, J., Demede, D., Perrotin, F., Cloarec, S., Vequeau-Goua, V., Descombes, E., Boulot, P., Morin, D., Fuchs, F., Tenenbaum, J., Ville, Y., Blanc, T., Heidet, L., Paris, A., Dobremez, E., Froute, M.F., Gondry, J., Muszynski, C., Haraux, E., Lobelle, F., Chevreau, J., Rosenblatt, J., Baudoin, V., Deschenes, G., Guigue, V., Amblard, F., Bourdat-Michel, G., Wühl, E., Schaefer, F., Elsässer, M., Persico, N., Rossi, F., Manzoni, G., De Marco, E.A., Montini, G., Capone, V., Caforio, L., Zaccara, A., Innocenzi, M., Bagolan, P., Capozza, N., Castagnetti, M., Mancini, M., Oepkes, D., van Scheltema, P.A., Feitz, W., Kortmann, B., Schreuder, M., Tkaczyk, M., Stańczyk, M., Szaflik, K., Wojtera, J., Krzeszowski, W., Talar, T., Pawłowska, B., Fortecka-Piestrzeniewicz, K., Olejniczak, D., Ariceta, G., Arevalo, S., Rodo, C., Fossum, M., Lindgren, P., Parvex, P., Chehade, H., Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Radboud University Medical Center [Nijmegen], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), HybridStat Predictive Analytics [Athens, Greece], Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), University Hospitals Leuven [Leuven], Heidelberg University Hospital [Heidelberg], University of Milan, Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico [Milan, Italy], Leiden University Medical Center (LUMC), Radboud Institute for Molecular Life Sciences [Nijmegen, the Netherlands], Polish Mother’s Memorial Hospital Research Institute [Lodz] (ICZMP), Pediatric Nephrology [Barcelona, Spain] (Vall d’Hebron Hospital), Universitat Autònoma de Barcelona (UAB)-Vall d'Hebron University Hospital [Barcelona], Karolinska University Hospital [Stockholm], Karolinska Institutet [Stockholm], Geneva University Hospital (HUG), Aarhus University Hospital, Aarhus University [Aarhus], Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, ANTENATAL Consortium: An Hindryckx, Luc De Catte, Christophe Vayssieres, Agnès Sartor, Marion Groussolles, Christelle Plard, Paul Guerby, Laure Connan, Mathieu Morin, Elizabeth Simon, Jean Breaud, Anne-Hélène Saliou, Loic De Parscau, Nadine Jay, Isabelle Germouty, Gwenaelle Le Bouar, Amelie Ryckewaert, Marie-Christine Manca-Pellissier, Thierry Merrot, Helene Laurichesse, Denis Gallot, Lucie Bessenay, Laurent Bidat, Philippe Boize, Norbert Winer, Emma Allain-Launey, Claudine Le Vaillant, Fabienne Prieur, Marie-Pierre Lavocat, Frederic Coatleven, Eric Debromez, Jérôme Harembat, Brigitte Llanas, Romain Favre, Raphael Moog, Ariane Zaloszyc, Jérôme Massardier, Delphine Demede, Franck Perrotin, Sylvie Cloarec, Valérie Vequeau-Goua, Emmanuelle Descombes, Pierre Boulot, Denis Morin, Florent Fuchs, Julie Tenenbaum, Yves Ville, Thomas Blanc, Laurence Heidet, Anne Paris, Eric Dobremez, Marie-Françoise Froute, Jean Gondry, Charles Muszynski, Elodie Haraux, Fabienne Lobelle, Julien Chevreau, Jonathan Rosenblatt, Véronique Baudoin, Georges Deschenes, Virginie Guigue, Florence Amblard, Guylhène Bourdat-Michel, Elke Wühl, Franz Schaefer, Michael Elsässer, Nicola Persico, Federica Rossi, Gianantonio Manzoni, Erika A De Marco, Giovanni Montini, Valentina Capone, Leonardo Caforio, Antonio Zaccara, Michele Innocenzi, Pietro Bagolan, Nicola Capozza, Marco Castagnetti, Mariangela Mancini, Dick Oepkes, Phebe Adama van Scheltema, Wout Feitz, Barbara Kortmann, Michiel Schreuder, Marcin Tkaczyk, Małgorzata Stańczyk, Krzysztof Szaflik, Justyna Wojtera, Waldemar Krzeszowski, Tomasz Talar, Barbara Pawłowska, Katarzyna Fortecka-Piestrzeniewicz, Dariusz Olejniczak, Gema Ariceta, Silvia Arevalo, Carlota Rodo, Magdalena Fossum, Peter Lindgren, Paloma Parvex, Hassib Chehade., Schanstra, Joost, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Università degli Studi di Milano = University of Milan (UNIMI)
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Posterior urethral valve ,medicine.medical_specialty ,Urinary system ,[SDV]Life Sciences [q-bio] ,kidney disease ,prenatal biomarkers ,Renal function ,Prenatal care ,030204 cardiovascular system & hematology ,DIAGNOSIS ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,0302 clinical medicine ,Medicine ,obstructive uropathy ,Obstructive uropathy ,development ,030304 developmental biology ,RISK ,0303 health sciences ,Transplantation ,Kidney ,ddc:618 ,Science & Technology ,business.industry ,Obstetrics ,Original Articles ,prediction ,Urology & Nephrology ,Omics ,medicine.disease ,6. Clean water ,3. Good health ,[SDV] Life Sciences [q-bio] ,Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10] ,Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] ,medicine.anatomical_structure ,Nephrology ,embryonic structures ,Settore MED/20 ,URINARY-TRACT OBSTRUCTION ,Renal disorders Radboud Institute for Health Sciences [Radboudumc 11] ,business ,Life Sciences & Biomedicine ,Kidney disease - Abstract
Altres ajuts: The study is partially made possible by support of the 'Programme Hospitalier de Recherche Clinique and 'La Foundation de la Recherche Médicale (grant number DEQ20170336759, France). M.T. was supported by the Polish Mothers Memorial Hospital Research Institute (internal grant number 2016/IV/54-GW. LvdZ is supported by a Kolff grant from the Dutch Kidney Foundation (13OKJ36) and a ZonMW-VENI grant from the Netherlands Organisation for Scientific Research (91618036). This project has been supported by ERN ERKNet and ERN eUROGEN, which are partly co-funded by the European Union within the framework of the Third Health Programme 'ERN-2016-Framework Partnership Agreement 2017-2021'. Posterior urethral valves (PUV) account for 17% of paediatric end-stage renal disease. A major issue in the management of PUV is prenatal prediction of postnatal renal function. Fetal ultrasound and fetal urine biochemistry are currently employed for this prediction, but clearly lack precision. We previously developed a fetal urine peptide signature that predicted in utero with high precision postnatal renal function in fetuses with PUV. We describe here the objectives and design of the prospective international multicentre ANTENATAL (multicentre validation of a fetal urine peptidome-based classifier to predict postnatal renal function in posterior urethral valves) study, set up to validate this fetal urine peptide signature. Participants will be PUV pregnancies enrolled from 2017 to 2021 and followed up until 2023 in >30 European centres endorsed and supported by European reference networks for rare urological disorders (ERN eUROGEN) and rare kidney diseases (ERN ERKNet). The endpoint will be renal/patient survival at 2 years postnatally. Assuming α = 0.05, 1-β = 0.8 and a mean prevalence of severe renal outcome in PUV individuals of 0.35, 400 patients need to be enrolled to validate the previously reported sensitivity and specificity of the peptide signature. In this largest multicentre study of antenatally detected PUV, we anticipate bringing a novel tool to the clinic. Based on urinary peptides and potentially amended in the future with additional omics traits, this tool will be able to precisely quantify postnatal renal survival in PUV pregnancies. The main limitation of the employed approach is the need for specialized equipment. Accurate risk assessment in the prenatal period should strongly improve the management of fetuses with PUV.
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- 2020
29. Cardiac rhabdomyoma with hydrops fetalis: Prenatal management by abdominal drainage
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Claudine Le Vaillant, Nadir Benbrik, Claire Beneteau, and Emeline Lefizelier
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medicine.medical_specialty ,Pregnancy ,Fetus ,Cardiac rhabdomyoma ,030219 obstetrics & reproductive medicine ,Obstetrics ,business.industry ,Obstetrics and Gynecology ,Peritoneal-amniotic shunting ,Hydrops ,Gynecology and obstetrics ,medicine.disease ,Asymptomatic ,Intracardiac injection ,Shunt (medical) ,Fetal ,03 medical and health sciences ,0302 clinical medicine ,Hydrops fetalis ,Ascites ,medicine ,RG1-991 ,Gestation ,medicine.symptom ,business - Abstract
Objective We described a case of fetal cardiac rhabdomyoma complicated by hydrops. And we discussed our approach during pregnancy. Case Report A 23-year-old woman primigravida was referred at 29 weeks of gestation (WG) to prenatal unit for a large hyperechogenic intracardiac mass associated with fetal hydrops. An intrauterine peritoneo-amniotic shunt was placed. Complete regression of ascites and pericardial effusions were observed after 34 WG with drain in good position. Conclusion Cardiac rhabdomyoma is the most common prenatal cardiac tumor. These tumors are benign, asymptomatic and spontaneously regress after birth. However, in some cases, these tumors may cause severe obstructions on the fetal heart and need specific treatment.
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- 2021
30. A multi-dimensional approach to the relationship between insight and aggressiveness in schizophrenia: Findings from the FACE-SZ cohort
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A. Schandrin, J. Norton, S. Raffard, B. Aouizerate, F. Berna, L. Brunel, I. Chereau-Boudet, T. D'Amato, H. Denizot, C. Dubertret, J. Dubreucq, C. Faget, G. Fond, F. Gabayet, P.M. Llorca, J. Mallet, D. Misdrahi, C. Passerieux, R. Rey, F. Schurhoff, M. Urbach, S. Bonnet, D. Capdevielle, M. Andrianarisoa, N. Bazin, O. Blanc, E. Bulzacka, G. Chesnoy-Servanin, J.M. Danion, A. Deloge, C. Delorme, J.M. Dorey, C. Fluttaz, S. Fonteneau, E. Giraud-Baro, D. Lacelle, C. Lançon, H. Laouamri, M. Leboyer, T. Le Gloahec, Y. Le Strat, E. Metairie, I. Offerlin-Meyer, P. Peri, S. Pires, C. Portalier, L. Ramet, L. Rey, C. Roman, F. Schürhoff, A. Tessier, A.M. Tronche, F. Vaillant, A. Vehier, P. Vidailhet, E. Vilà, H. Yazbek, A. Zinetti-Bertschy, Université Montpellier 1 (UM1), Fondation FondaMental [Créteil], Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institut Européen des membranes (IEM), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), Psychopathologie et pharmacologie de la cognition, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier le Vinatier [Bron], Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA), Mécanique des Fluides, Energies et Environnement (EDF R&D MFEE), EDF R&D (EDF R&D), EDF (EDF)-EDF (EDF), Aix Marseille Université (AMU), Assistance Publique-Hôpitaux de Marseille (AP-HM), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), 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), Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Universitaire [Grenoble] (CHU), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), CCSD, Accord Elsevier, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital de la Colombière, Centre hospitalier Charles Perrens [Bordeaux], Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie (NCPS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg, CHU Strasbourg, Pôle de psychiatrie et d'addictologie des Hôpitaux Universitaires Henri-Mondor [Créteil], Centre hospitalier universitaire Henri-Mondor [Créteil], CHU Clermont-Ferrand, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Référent de Réhabilitation Psychosociale [CH Alpes Isère], Centre Hospitalier Alpes Isère, Centre Hospitalier de Versailles André Mignot (CHV), Laboratoire de recherches cliniques et en santé publique sur les handicaps psychique, cognitif et moteur (HANDIReSP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Montpellier (UM), FACE-SZ (FondaMental Academic Centers of Expertise for Schizophrenia) group: M Andrianarisoa 16 , B Aouizerate 17 , N Bazin 18 , F Berna 19 , O Blanc 20 , L Brunel 16 , E Bulzacka 16 , D Capdevielle 21 , I Chereau-Boudet 20 , G Chesnoy-Servanin 22 , J M Danion 19 , T D'Amato 22 , A Deloge 23 , C Delorme 24 , H Denizot 20 , J M Dorey 22 , C Dubertret 25 , J Dubreucq 24 , C Faget 26 , C Fluttaz 24 , G Fond 27 , S Fonteneau 18 , F Gabayet 24 , E Giraud-Baro 24 , D Lacelle 20 , C Lançon 26 , H Laouamri 27 , M Leboyer 16 , T Le Gloahec 16 , Y Le Strat 25 , P M Llorca 20 , J Mallet 25 , E Metairie 26 , D Misdrahi 23 , I Offerlin-Meyer 19 , C Passerieux 18 , P Peri 26 , S Pires 20 , C Portalier 25 , L Ramet 18 , L Rey 22 , C Roman 24 , A Schandrin 28 , F Schürhoff 16 , A Tessier 23 , A M Tronche 20 , M Urbach 18 , F Vaillant 26 , A Vehier 22 , P Vidailhet 19 , E Vilà 23 , H Yazbek 21 , A Zinetti-Bertschy 19, Hôpital Charles Perrens, Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Université d'Auvergne - Clermont-Ferrand I (UdA)-CHU Clermont-Ferrand, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie de la Plasticité Neuronale (Neurocentre Magendie - U1215 Inserm), and Centre de Psychiatrie et Neurosciences (U894)
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Adult ,Male ,Adolescent ,media_common.quotation_subject ,[SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health ,Hostility ,Anger ,Cohort Studies ,Diagnostic Self Evaluation ,Young Adult ,03 medical and health sciences ,Aggressiveness ,0302 clinical medicine ,medicine ,Humans ,Spectrum disorder ,ComputingMilieux_MISCELLANEOUS ,Biological Psychiatry ,media_common ,Aggression ,Middle Aged ,Awareness ,030227 psychiatry ,3. Good health ,Psychiatry and Mental health ,Psychotic Disorders ,[SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health ,Cohort ,Schizophrenia ,Multi dimensional ,Female ,medicine.symptom ,Insight ,Psychology ,030217 neurology & neurosurgery ,Diagnosis of schizophrenia ,Clinical psychology - Abstract
International audience; Background: Aggressiveness is a stigma frequently associated with schizophrenia. The role of insight as a risk factor of aggressiveness remains contradictory; mainly because single measures of these states mask their complexity and heterogeneity.Methods: This study was conducted on 666 patients aged 15 and above with a DSM-IV-TR diagnosis of schizophrenia spectrum disorder, drawn from the French national network of schizophrenia expert center database. Collected data comprised socio-demographics and standardized psychiatric assessments. Aggressiveness was evaluated using the Buss-Perry Aggression Questionnaire and insight using the Scale to assess Unawareness of Mental Disorder (SUMD) and Birchwood Insight Scale (BIS).Results: Hostility was the aggressiveness dimension the most strongly associated with SUMD insight dimensions. Patients aware of their illness were nearly twice as likely to show hostility than those seriously unaware (OR = 1.95, 95% CI.: 1.08-3.5), but not when further adjusting for depression. Similarly, those aware of the consequences of their illness and of their symptoms were more hostile. Patients moderately aware of illness consequences had a higher risk of both anger and physical aggressiveness than those unaware (OR = 2.63, 95% CI.: 1.42-4.86, OR = 2.47, 95% CI.: 1.33-4.60, respectively), even when adjusting for depression for anger.Conclusion: Our study confirms that a multi-dimensional approach to insight and aggressiveness is essential to understand the types of links between these clinical states. Insight may trigger the expression of an underlying hostile tendency, maybe via depression and self-stigmatisation. This should be taken into account in therapeutic approaches to improve insight.
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- 2019
31. The Clinical Non-Motor Connectome in Early Parkinson’s Disease
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Michel Vaillant, Nico J. Diederich, Vannina Pieri, Nicolas Sauvageot, and Geraldine Hipp
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Research Report ,Male ,Sleep Wake Disorders ,medicine.medical_specialty ,Parkinson's disease ,Disease ,compensation ,Correlation ,Olfaction Disorders ,Cellular and Molecular Neuroscience ,Internal medicine ,medicine ,Humans ,Cognitive Dysfunction ,Stage (cooking) ,Prospective cohort study ,Aged ,Models, Statistical ,Mood Disorders ,business.industry ,connectome ,Parkinson Disease ,Cognition ,Middle Aged ,bacterial infections and mycoses ,medicine.disease ,non-motor symptoms ,Mood ,Autonomic Nervous System Diseases ,Parkinson’s disease ,Disease Progression ,Connectome ,Female ,Neurology (clinical) ,business ,Follow-Up Studies - Abstract
Background: Non-motor symptoms (NMS) of various anatomical origins are seen in early stage idiopathic Parkinson’s disease (IPD). Objective: To analyse when and how NMS are linked together at this stage of the disease. Methods: Prospective study recruiting 64 IPD patients with ≤3 years of disease duration and 71 age-matched healthy controls (HC). NMS were clustered in 7 non-motor domains (NMD): general cognition, executive function, visuospatial function, autonomic function, olfaction, mood, and sleep. Correlation coefficients ≥|0.3| were considered as significant. Bootstrapped correlation coefficients between the scores were generated in both groups. Fourteen IPD patients and 19 HC were available for a follow-up study two years later. Results: The mean age of both groups was similar. 58% of IPD patients and 37% of HC were male (p = 0.01). At baseline IPD patients performed less well than HC on all NMD (p value between 0.0001 and 0.02). Out of 91 possible correlations between NMD, 21 were significant in IPD patients and 14 in HC at the level of ≥|0.3|. The mean correlation level was higher in IPD patients than in HC, as evidenced by the higher box plot of correlation coefficients. Visuospatial scores at baseline were predictive of the motor deterioration at the follow-up exam. Conclusion: At early IPD stage various NMS are linked together, although not connected by anatomical networks. Such a clinical NMD connectome suggests almost synchronous disease initiation at different sites as also supported by fMRI findings. Alternatively, there may be compensation-driven interconnectivity of NMD.
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- 2020
32. Pathogenic variants in actionable MODY genes are associated with type 2 diabetes
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Elizabeth T. Cirulli, Nicole L. Washington, Mickaël Canouil, Guillaume Charpentier, Emmanuelle Durand, Jean-Michel Borys, Alexandre Bolze, Franck De Graeve, Aurélie Dechaume, David Le Guilcher, Beverley Balkau, Sylvia Franc, Frédéric Allegaert, Ronan Roussel, Emmanuel Vaillant, Philippe Froguel, Gai Elhanan, Stefan Gaget, Joseph J. Grzymski, Loic Yengo, Véronique Dhennin, Amélie Bonnefond, James T. Lu, M Vaxillaire, Mathilde Boissel, Michel Marre, Bénédicte Toussaint, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, and ANR-18-IBHU-0001,PreciDIAB,PreciDIAB Institute, the holistic approach of personal diabets care(2018)
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Male ,Heterozygote ,MESH: Mutation ,endocrine system diseases ,[SDV]Life Sciences [q-bio] ,Endocrinology, Diabetes and Metabolism ,Type 2 diabetes ,ABCC8 ,Germinal Center Kinases ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,MESH: Genetic Variation ,Gene ,030304 developmental biology ,Monogenic Diabetes ,Genetic association ,Genetics ,0303 health sciences ,MESH: Humans ,biology ,business.industry ,Computational Biology ,Genetic Variation ,nutritional and metabolic diseases ,Cell Biology ,Middle Aged ,medicine.disease ,Precision medicine ,HNF1B ,3. Good health ,Diabetes Mellitus, Type 2 ,Mutation ,MESH: Genome-Wide Association Study ,biology.protein ,Female ,business ,030217 neurology & neurosurgery ,Genome-Wide Association Study ,MESH: Computational Biology ,MESH: Diabetes Mellitus, Type 2 - Abstract
International audience; Genome-wide association studies have identified 240 independent loci associated with type 2 diabetes (T2D) risk, but this knowledge has not advanced precision medicine. In contrast, the genetic diagnosis of monogenic forms of diabetes (including maturity-onset diabetes of the young (MODY)) are textbook cases of genomic medicine. Recent studies trying to bridge the gap between monogenic diabetes and T2D have been inconclusive. Here, we show a significant burden of pathogenic variants in genes linked with monogenic diabetes among people with common T2D, particularly in actionable MODY genes, thus implying that there should be a substantial change in care for carriers with T2D. We show that, among 74,629 individuals, this burden is probably driven by the pathogenic variants found in GCK, and to a lesser extent in HNF4A, KCNJ11, HNF1B and ABCC8. The carriers with T2D are leaner, which evidences a functional metabolic effect of these mutations. Pathogenic variants in actionable MODY genes are more frequent than was previously expected in common T2D. These results open avenues for future interventions assessing the clinical interest of these pathogenic mutations in precision medicine.
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- 2020
33. A CPAP data–based algorithm for automatic early prediction of therapy adherence
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Marc Le Vaillant, N. Meslier, Frédéric Gagnadoux, Laurene Leclair-Visonneau, François Goupil, Marie-Pierre Humeau, Philippe Masson, AbdelKebir Sabil, Christy J. Stitt, Thierry Pigeanne, and Acya Bizieux-Thaminy
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medicine.medical_specialty ,Univariate analysis ,Multivariate analysis ,business.industry ,medicine.medical_treatment ,Retrospective cohort study ,medicine.disease ,respiratory tract diseases ,Discontinuation ,Obstructive sleep apnea ,03 medical and health sciences ,0302 clinical medicine ,030228 respiratory system ,Otorhinolaryngology ,Cohort ,medicine ,Neurology (clinical) ,Continuous positive airway pressure ,business ,Algorithm ,030217 neurology & neurosurgery - Abstract
Adherence is a critical issue in the treatment of obstructive sleep apnea with continuous positive airway pressure (CPAP). Approximately 40% of patients treated with CPAP are at risk of discontinuation or insufficient use (< 4 h/night). Assuming that the first few days on CPAP are critical for continued treatment, we tested the predictive value at day 14 (D14) of the Philips Adherence Profiler™ (AP) algorithm for adherence at 3 months (D90). The AP™ algorithm uses CPAP machine data hosted in the database of EncoreAnywhere™. This retrospective study involved 457 patients (66% men, 60.0 ± 11.9 years; BMI = 31.2 ± 5.9 kg/m2; AHI = 37.8 ± 19.2; Epworth score = 10.0 ± 4.8) from the Pays de la Loire Sleep Cohort. At D90, 88% of the patients were adherent as defined by a mean daily CPAP use of ≥ 4 h. In a univariate analysis, the factors significantly associated with CPAP adherence at D90 were older age, lower BMI, CPAP adherence (≥ 4 h/night) at D14, and AP™ prediction at D14. In a multivariate analysis, only older age (OR 2.10 [1.29–3.41], p = 0.003) and the AP™ prediction at D14 (OR 16.99 [7.26–39.75], p < 0.0001) were significant predictors. CPAP adherence at D90 was not associated with device-derived residual events, nor with the levels of pressure or leakage except in the case of very significant leakage when it persisted for 90 days. Automatic telemonitoring algorithms are relevant tools for early prediction of CPAP therapy adherence and may make it possible to focus therapeutic follow-up efforts on patients who are at risk of non-adherence.
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- 2020
34. Factors associated with spoken language comprehension in children with cerebral palsy: a systematic review
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R. Jeroen Vermeulen, A.I. Buizer, Emma Vaillant, Kim J. Oostrom, Elise P. Jansma, and Johanna Geytenbeek
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PRESCHOOL-CHILDREN ,YOUNG-CHILDREN ,Adolescent ,school ,speech ,icf-cy ,Psychological intervention ,Developmental cognitive neuroscience ,Reviews ,Context (language use) ,PsycINFO ,Cochrane Library ,MANUAL ABILITY ,Cerebral palsy ,Developmental psychology ,aged children ,03 medical and health sciences ,0302 clinical medicine ,Borderline intellectual functioning ,Developmental Neuroscience ,International Classification of Functioning, Disability and Health ,030225 pediatrics ,medicine ,Humans ,Child ,Language ,communication ,GROSS MOTOR FUNCTION ,Cerebral Palsy ,Infant ,non-speaking children ,medicine.disease ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Speech Perception ,Neurology (clinical) ,Systematic Review ,Psychology ,Comprehension ,030217 neurology & neurosurgery - Abstract
AIM: To identify factors that are relevant for spoken language comprehension in children with cerebral palsy (CP), following the International Classification of Functioning, Disability and Health - Children and Youth (ICF-CY) framework.METHOD: A systematic literature search was conducted using the electronic literature databases PubMed, Embase, PsycInfo, and Cochrane Library, from January 1967 to December 2019. Included studies involved children with CP, results regarding spoken language comprehension, and analysis of at least one associated factor. Factors were classified within ICF-CY domains.RESULTS: Twenty-one studies met inclusion criteria. Factors in the ICF-CY domains of body functions and structure were most frequently reported. White brain matter abnormalities, motor type, functional mobility, and intellectual functioning appear to be relevant factors in spoken language comprehension in CP. Factors in the domain of activities and participation, as well as contextual factors, have rarely been studied in the context of spoken language comprehension in CP.INTERPRETATION: Most factors known to be important for spoken language comprehension in typically developing children and/or known to be susceptible to change by interventions are understudied in CP.
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- 2020
35. Social support as protective factor of the effects of part-time work on psychological health: a moderated mediation model
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Damien Vaillant, N. Mellor, Maria Karanika-Murray, George Michaelides, and Laurence Saunder
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Value (ethics) ,Public Health, Environmental and Occupational Health ,Protective factor ,Context (language use) ,030210 environmental & occupational health ,Structural equation modeling ,Developmental psychology ,03 medical and health sciences ,Social support ,0302 clinical medicine ,Moderated mediation ,Psychological well-being ,medicine ,Business, Management and Accounting (miscellaneous) ,Anxiety ,030212 general & internal medicine ,medicine.symptom ,Psychology - Abstract
PurposeThe purpose of this study is to examine the protective effect of social support on psychological health and how it differs by gender in the context of part-time employment.Design/methodology/approachThe sample consisted of 22,786 employees from four service sector organisations. Structural equation modelling was used to test a moderated mediation model assessing the relationship between employment status (part-time vs full-time) and psychological health mediated by social support (from management and colleagues) and moderated by gender.FindingsSocial support from management and colleagues was associated with fewer symptoms of stress, anxiety and depression. Notably, management support had a stronger association than that of colleagues’ support on each of the three health-related variables. Social support was also found to be a mediator of part-time working on health such that lower social support led to increased health symptoms. Moreover, we found moderating gender effects between social support and psychological health such that colleague support had a stronger effect on reduced depression and stress among men than women whilst management support had a stronger effect on reduced anxiety for women. Finally, significant moderated mediating paths were found, but further research is needed to identify other potential moderators of the mediating effects.Originality/valueThe findings suggest complex relationships between part-time employment, social support, psychological health and gender not examined in previous studies. It highlights the value of diverse sources of support and the necessity of addressing specific gender's needs for enhancing psychological health of part-time employees.
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- 2020
36. Parkinson’s disease-associated alterations of the gut microbiome predict disease-relevant changes in metabolic functions
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Baldini, Federico, Hertel, Johannes, Sandt, Estelle, Thinnes, Cyrille C., Neuberger-Castillo, Lorieza, Pavelka, Lukas, Betsou, Fay, Krüger, Rejko, Thiele, Ines, Aguayo, Gloria, Allen, Dominic, Ammerlann, Wim, Aurich, Maike, Balling, Rudi, Banda, Peter, Beaumont, Katy, Becker, Regina, Berg, Daniela, Binck, Sylvia, Bisdorff, Alexandre, Bobbili, Dheeraj, Brockmann, Kathrin, Calmes, Jessica, Castillo, Lorieza, Diederich, Nico, Dondelinger, Rene, Esteves, Daniela, Ferrand, Jean-Yves, Fleming, Ronan, Gantenbein, Manon, Gasser, Thomas, Gawron, Piotr, Geffers, Lars, Giarmana, Virginie, Glaab, Enrico, Gomes, Clarissa P. C., Goncharenko, Nikolai, Graas, Jérôme, Graziano, Mariela, Groues, Valentin, Grünewald, Anne, Gu, Wei, Hammot, Gaël, Hanff, Anne-Marie, Hansen, Linda, Hansen, Maxime, Haraldsdöttir, Hulda, Heirendt, Laurent, Herbrink, Sylvia, Herzinger, Sascha, Heymann, Michael, Hiller, Karsten, Hipp, Geraldine, Hu, Michele, Huiart, Laetitia, Hundt, Alexander, Jacoby, Nadine, Jarosław, Jacek, Jaroz, Yohan, Kolber, Pierre, Kutzera, Joachim, Landoulsi, Zied, Larue, Catherine, Lentz, Roseline, Liepelt, Inga, Liszka, Robert, Longhino, Laura, Lorentz, Victoria, Mackay, Clare, Maetzler, Walter, Marcus, Katrin, Marques, Guilherme, Martens, Jan, Mathay, Conny, Matyjaszczyk, Piotr, May, Patrick, Meisch, Francoise, Menster, Myriam, Minelli, Maura, Mittelbronn, Michel, Mollenhauer, Brit, Mommaerts, Kathleen, Moreno, Carlos, Mühlschlegel, Friedrich, Nati, Romain, Nehrbass, Ulf, Nickels, Sarah, Nicolai, Beatrice, Nicolay, Jean-Paul, Noronha, Alberto, Oertel, Wolfgang, Ostaszewski, Marek, Pachchek, Sinthuja, Pauly, Claire, Perquin, Magali, Reiter, Dorothea, Rosety, Isabel, Rump, Kirsten, Satagopam, Venkata, Schlesser, Marc, Schmitz, Sabine, Schmitz, Susanne, Schneider, Reinhard, Schwamborn, Jens, Schweicher, Alexandra, Simons, Janine, Stute, Lara, Trefois, Christophe, Trezzi, Jean-Pierre, Vaillant, Michel, Vasco, Daniel, Vyas, Maharshi, Wade-Martins, Richard, and Wilmes, Paul
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Male ,Systemic disease ,Parkinson's disease ,Physiology ,Luxembourg ,Plant Science ,Disease ,Transsulfuration pathway ,Biology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Structural Biology ,RNA, Ribosomal, 16S ,Pantothenic acid ,medicine ,Humans ,Microbiome ,lcsh:QH301-705.5 ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,Aged ,Metabolic modelling ,0303 health sciences ,Gut microbiome ,Methionine ,Dopaminergic ,Parkinson Disease ,Cell Biology ,Middle Aged ,medicine.disease ,3. Good health ,Gastrointestinal Microbiome ,RNA, Bacterial ,chemistry ,Computational modelling ,lcsh:Biology (General) ,Case-Control Studies ,Parkinson’s disease ,Female ,General Agricultural and Biological Sciences ,030217 neurology & neurosurgery ,Developmental Biology ,Biotechnology ,Research Article - Abstract
Background Parkinson’s disease (PD) is a systemic disease clinically defined by the degeneration of dopaminergic neurons in the brain. While alterations in the gut microbiome composition have been reported in PD, their functional consequences remain unclear. Herein, we addressed this question by an analysis of stool samples from the Luxembourg Parkinson’s Study (n = 147 typical PD cases, n = 162 controls). Results All individuals underwent detailed clinical assessment, including neurological examinations and neuropsychological tests followed by self-reporting questionnaires. Stool samples from these individuals were first analysed by 16S rRNA gene sequencing. Second, we predicted the potential secretion for 129 microbial metabolites through personalised metabolic modelling using the microbiome data and genome-scale metabolic reconstructions of human gut microbes. Our key results include the following. Eight genera and seven species changed significantly in their relative abundances between PD patients and healthy controls. PD-associated microbial patterns statistically depended on sex, age, BMI, and constipation. Particularly, the relative abundances of Bilophila and Paraprevotella were significantly associated with the Hoehn and Yahr staging after controlling for the disease duration. Furthermore, personalised metabolic modelling of the gut microbiomes revealed PD-associated metabolic patterns in the predicted secretion potential of nine microbial metabolites in PD, including increased methionine and cysteinylglycine. The predicted microbial pantothenic acid production potential was linked to the presence of specific non-motor symptoms. Conclusion Our results suggest that PD-associated alterations of the gut microbiome can translate into substantial functional differences affecting host metabolism and disease phenotype.
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- 2020
37. Cholangiocarcinoma Following Bariatric Surgery: a Prospective Follow-Up Single-Center Audit
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Jean-Michel Siksik, Nassiba Beghdadi, Laurent Genser, Jean-Christophe Vaillant, Judith Aron-Wisnewsky, Celia Turco, Chetana Lim, Olivier Scatton, Claire Goumard, Adriana Torcivia, and Jean-Michel Oppert
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medicine.medical_specialty ,Percutaneous ,Endocrinology, Diabetes and Metabolism ,Gastric Bypass ,Bariatric Surgery ,030209 endocrinology & metabolism ,Single Center ,Cholangiocarcinoma ,Biliary disease ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Prospective Studies ,Retrospective Studies ,Nutrition and Dietetics ,business.industry ,Incidence (epidemiology) ,Cancer ,Jaundice ,medicine.disease ,Obesity, Morbid ,Surgery ,Obstructive sleep apnea ,Bile Ducts, Intrahepatic ,Bile Duct Neoplasms ,Diabetes Mellitus, Type 2 ,030211 gastroenterology & hepatology ,medicine.symptom ,business ,Dyslipidemia ,Follow-Up Studies - Abstract
Cholangiocarcinoma (CC) incidence is rising worldwide. Obesity and its related metabolic impairments are associated with primitive liver malignancies including CC. While bariatric surgery (BS) is associated with decreased risk of incident cancer, few data are available regarding CC incidence, presentation, and management issues after BS. We retrospectively reviewed collected data on 1911 consecutive patients undergoing BS from 2010 to 2019. We recorded three cases (0.16%) of CC during the postoperative follow-up. All cases underwent a Roux-en-Y gastric bypass (RYGB) for class III obesity with metabolic diseases (i.e., type 2 diabetes mellitus, hypertension, dyslipidemia, and obstructive sleep apnea) without any personal or familial history of biliary disease. The patients presented with an inaugural jaundice or pruritus at 8, 12, and 13 months after RYBG, which enabled the diagnosis of metastatic CCs in all cases. In such palliative setting without access to the pancreato-biliary system, biliary drainage was ensured by a percutaneous trans-hepatic biliary drain. Chemotherapy was initiated in two patients. All the patients died within a delay of 2, 11, and 17 months after the diagnosis, respectively. The incidence of post-BS CC appears low, but the prognosis is poor because of advanced stages at diagnosis. These cases illustrate the difficulty to make both on-time diagnosis and optimal management of CC especially in patients operated of RYGB with limited access to the excluded anatomy.
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- 2020
38. Genetic Causes of Severe Childhood Obesity: A Remarkably High Prevalence in an Inbred Population of Pakistan
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Emmanuel Vaillant, Taeed A. Butt, Philippe Froguel, Sadia M. Din, Mehdi Derhourhi, Emmanuelle Durand, Hina Ayesha, Souhila Amanzougarene, Laraib Inam, Qasim M. Janjua, Muhammad Arslan, Qura-tul Ain, Stéphane Lobbens, Alaa Badreddine, Stefan Gaget, Jaida Manzoor, Amélie Bonnefond, Waqas I. Khan, Sadia Saeed, and Lionel Berberian
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Leptin ,Male ,0301 basic medicine ,Proband ,Pediatric Obesity ,Candidate gene ,Adolescent ,DNA Copy Number Variations ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Biology ,Childhood obesity ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Intellectual disability ,Prevalence ,Internal Medicine ,medicine ,Humans ,Copy-number variation ,Child ,Genetics ,Point mutation ,Infant ,medicine.disease ,Obesity ,Obesity, Morbid ,030104 developmental biology ,Child, Preschool ,Mutation ,Cohort ,Receptor, Melanocortin, Type 4 ,Receptors, Leptin ,Female - Abstract
Monogenic forms of obesity have been identified in ≤10% of severely obese European patients. However, the overall spectrum of deleterious variants (point mutations and structural variants) responsible for childhood severe obesity remains elusive. In this study, we genetically screened 225 severely obese children from consanguineous Pakistani families through a combination of techniques, including an in-house–developed augmented whole-exome sequencing method (CoDE-seq) that enables simultaneous detection of whole-exome copy number variations (CNVs) and point mutations in coding regions. We identified 110 (49%) probands carrying 55 different pathogenic point mutations and CNVs in 13 genes/loci responsible for nonsyndromic and syndromic monofactorial obesity. CoDE-seq also identified 28 rare or novel CNVs associated with intellectual disability in 22 additional obese subjects (10%). Additionally, we highlight variants in candidate genes for obesity warranting further investigation. Altogether, 59% of cases in the studied cohort are likely to have a discrete genetic cause, with 13% of these as a result of CNVs, demonstrating a remarkably higher prevalence of monofactorial obesity than hitherto reported and a plausible overlapping of obesity and intellectual disabilities in several cases. Finally, inbred populations with a high prevalence of obesity provide unique, genetically enriched material in the quest of new genes/variants influencing energy balance.
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- 2020
39. Targeting triple-negative breast cancers with the Smac-mimetic birinapant
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John Silke, Cathrine Hall, Matthias Ernst, Jean Berthelet, Bhupinder Pal, David L. Vaux, Julius Gräsel, Lin Liu, Jane E. Visvader, Göknur Giner, Najoua Lalaoui, Delphine Merino, Tobias Kratina, James R. Whittle, Nima Etemadi, Gordon K. Smyth, Diep Chau, Matthew E. Ritchie, Geoffrey J. Lindeman, and François Vaillant
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Programmed cell death ,Indoles ,Antineoplastic Agents ,Triple Negative Breast Neoplasms ,Mice, SCID ,Inhibitor of apoptosis ,Article ,Transcriptome ,Mice ,RIPK1 ,Breast cancer ,Mice, Inbred NOD ,In vivo ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Molecular Biology ,Cancer ,Mice, Knockout ,business.industry ,Dipeptides ,Cell Biology ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Docetaxel ,Preclinical research ,Cancer research ,Female ,Tumor necrosis factor alpha ,biological phenomena, cell phenomena, and immunity ,business ,medicine.drug - Abstract
Smac mimetics target inhibitor of apoptosis (IAP) proteins, thereby suppressing their function to facilitate tumor cell death. Here we have evaluated the efficacy of the preclinical Smac-mimetic compound A and the clinical lead birinapant on breast cancer cells. Both exhibited potent in vitro activity in triple-negative breast cancer (TNBC) cells, including those from patient-derived xenograft (PDX) models. Birinapant was further studied using in vivo PDX models of TNBC and estrogen receptor-positive (ER+) breast cancer. Birinapant exhibited single agent activity in all TNBC PDX models and augmented response to docetaxel, the latter through induction of TNF. Transcriptomic analysis of TCGA datasets revealed that genes encoding mediators of Smac-mimetic-induced cell death were expressed at higher levels in TNBC compared with ER+ breast cancer, resulting in a molecular signature associated with responsiveness to Smac mimetics. In addition, the cell death complex was preferentially formed in TNBCs versus ER+ cells in response to Smac mimetics. Taken together, our findings provide a rationale for prospectively selecting patients whose breast tumors contain a competent death receptor signaling pathway for the further evaluation of birinapant in the clinic.
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- 2020
40. Tissue-resident ductal macrophages survey the mammary epithelium and facilitate tissue remodelling
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Jane E. Visvader, Scott N. Mueller, Florent Ginhoux, Camille Blériot, Geoffrey J. Lindeman, Caleb A. Dawson, Anne C. Rios, Bhupinder Pal, Zhaoyuan Liu, François Vaillant, Luke C. Gandolfo, and Gordon K. Smyth
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Population ,Biology ,Epithelium ,Monocytes ,Flow cytometry ,Mice ,03 medical and health sciences ,Mammary Glands, Animal ,0302 clinical medicine ,Immune system ,Phagocytosis ,Pregnancy ,medicine ,Animals ,Lactation ,Involution (medicine) ,education ,Cell Proliferation ,030304 developmental biology ,0303 health sciences ,education.field_of_study ,medicine.diagnostic_test ,Macrophages ,Epithelial Cells ,Cell Biology ,Embryonic stem cell ,Cell biology ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Mammary Epithelium ,030220 oncology & carcinogenesis ,Female ,Stem cell - Abstract
Macrophages are diverse immune cells that reside in all tissues. Although macrophages have been implicated in mammary-gland function, their diversity has not been fully addressed. By exploiting high-resolution three-dimensional imaging and flow cytometry, we identified a unique population of tissue-resident ductal macrophages that form a contiguous network between the luminal and basal layers of the epithelial tree throughout postnatal development. Ductal macrophages are long lived and constantly survey the epithelium through dendrite movement, revealed via advanced intravital imaging. Although initially originating from embryonic precursors, ductal macrophages derive from circulating monocytes as they expand during puberty. Moreover, they undergo proliferation in pregnancy to maintain complete coverage of the epithelium in lactation, when they are poised to phagocytose milk-producing cells post-lactation and facilitate remodelling. Interestingly, ductal macrophages strongly resemble mammary tumour macrophages and form a network that pervades the tumour. Thus, the mammary epithelium programs specialized resident macrophages in both physiological and tumorigenic contexts.
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- 2020
41. Topical rapamycin versus betamethasone dipropionate ointment for treating oral erosive lichen planus: a randomized, double‐blind, controlled study
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P. Bernard, Sophie Leducq, F. Boralevi, A. Le Gouge, Loïc Vaillant, F. Pascal, Camille Francès, Jean-Christophe Fricain, S. Agbo-Godeau, Mahtab Samimi, T. Passeron, Service de dermatologie (CHRU de Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Infectiologie et Santé Publique (UMR ISP), Université de Tours-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), U1035 Centre de R ef erence pour les Maladies Rares de la Peau, Service de Dermatologie Adulte et Pédiatrique, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de dermatologie (CHU de Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de Stomatologie et Chirurgie Maxillo-facial [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dermatologie et allergologie [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), French Ministry of Social Affairs and Health (French National Programme of Clinical Research [PHRC]), 2005, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Food intake ,medicine.medical_specialty ,Administration, Topical ,[SDV]Life Sciences [q-bio] ,Betamethasone dipropionate ,Dermatology ,Betamethasone ,Ointments ,Double blind ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,medicine ,Humans ,Psoriasis ,Adverse effect ,Sirolimus ,business.industry ,030206 dentistry ,Odds ratio ,3. Good health ,Treatment Outcome ,Infectious Diseases ,Clinical recurrence ,Neoplasm Recurrence, Local ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,[SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology ,After treatment ,Lichen Planus, Oral ,medicine.drug - Abstract
International audience; Background Although superpotent topical corticosteroids are the first-line treatment for oral erosive lichen planus (OELP), topical rapamycin was found efficient in a previous case series.Objectives To compare the efficacy and safety of topical rapamycin and betamethasone dipropionate ointment for OELP in a randomized, double-blind trial.Methods Patients were randomized to receive treatment with betamethasone dipropionate ointment 0.05% in Orabase(R) or topical rapamycin solution (1 mg/mL) on lesions twice daily for 3 months, followed by 3 months of observation. The primary outcome was clinical remission after 3 months of treatment. Secondary outcomes were clinical remission after 1 and 2 months, reduced oral pain and reduced impact on food intake after 3 months, clinical recurrence after treatment withdrawal, and adverse events.Results During a 4-year period, 76 patients were randomized and 75 received treatment (rapamycin, n = 39; betamethasone, n = 36). At 3 months, 39.4% of patients with betamethasone and 27.3% with rapamycin showed clinical remission (odds ratio 0.68, 95% CI [0.24; 1.89]; P = 0.46). Rates of remission after 1 and 2 months, reduction in pain and impact on food intake after 3 months, were higher with betamethasone than rapamycin. Recurrence of oral erosions was similar between groups. Adverse events occurred in 43.6% of patients with rapamycin (mostly burning sensation, impaired taste) and 27.8% with betamethasone (mostly oral candidiasis).Conclusion Although the study was limited by insufficient recruitment, we did not find any superiority of topical rapamycin over betamethasone dipropionate ointment for OELP. Given the rapid remission and pain improvement in the betamethasone group, it appears that superpotent topical corticosteroids should remain the first-line treatment for OELP.
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- 2020
42. Abstract P4-12-32: Intensity modulated radiotherapy (IMRT) for breast and lymph node irradiation
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Alain Fourquet, M. Robilliard, Youlia M. Kirova, F. Goudjil, Wassim El Amine, Laurent Bartolucci, Marion Vaillant, Marie Lejars, Camille Adrien, Alejandro Mazal, and E. Costa
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Cancer Research ,education.field_of_study ,Side effect ,business.industry ,medicine.medical_treatment ,Population ,Cancer ,medicine.disease ,Tomotherapy ,medicine.anatomical_structure ,Breast cancer ,Oncology ,Medicine ,Intensity modulated radiotherapy ,education ,business ,Nuclear medicine ,Proton therapy ,Lymph node - Abstract
Background:Since 2009, the use of IMRT for the treatment of breast cancer with lymph node involvement has been considerably growing at our institution. Helical Tomotherapy (HT) was chosen as main technique using field width of 2.5 cm (HT_FW_2.5). Alternatively HT using field width of 5 cm (HT_FW_5), Volumetric Modulated Arc Therapy (VMAT), or Proton Therapy with Pencil Beam Scanning (PT-PBS) were used to reduce treatment duration or optimize organs at risk (OAR) sparing. Purpose: the aim of this study is to compare the 4 modalities of treatment available at our site. Patients and methods: We studied 10 patients treated for breast cancer with lymph node involvement. The prescribed dose was 51.8 Gy to breast with simultaneous integrated boost till 63 Gy, 50.4 Gy to the lymph nodes in 28 fractions for all studied patients. The CTV (clinical target volume) were delineated using ESTRO Guidelines. Dosimetric plan used in routine clinical practice was done using HT_FW_2.5. Clinical plan approved was compared to the plan using the 3 others IMRT techniques. Dosimetric parameters were noted down. For Planning Target Volume (PTV) coverage, dosimetric goals were D95% ≥ 95% and D2% ≤ 107% of the prescribed dose. Regarding OAR, mean dose were noted for heart, contralateral/ipsilateral lung and contralateral breast. Maximum dose in the spinal cord was also recorded. Dosimetric score was made to evaluate plan quality. For both PTV score (PTVs) and OAR score (OARs), 1 was the best and 4 the worst achievable score. Results:HT_FW_5 and VMAT plans ensure an equivalent or even better PTV coverage than the initial clinically approved plan (PTVs = 2.3 and 2.0 VS 2.5) but at the cost of a deterioration of OAR sparing (OARs = 3.3 and 3.2 VS 2.3). PT_PBS plans show that an excellent PTV coverage can be maintained with significantly lower doses to OAR (PTVs = 2.0; OARs = 1.1) Conclusion:HT_FW_5 and VMAT plans allow significantly reducing treatment duration and can be good alternative to HT_FW_2.5 for specified population which has already a good OAR sparing and needs to reduce treatment duration. HT_FW_2.5 could be chosen for patient with higher risk of side effect. In addition PT_PBS treatment should be considered in the near future as it showed great potential benefit to lower the risk of side effects without deteriorating PTV coverage. Dosimetric Scores of different IMRT techniquesHT_FW_2,5HT_FW_5VMATPT_PBSD95% (Gy)PTV Breast49.449.950.149.7PTV Tumor Bed60.160.160.361.1PTV Lymph Nodes47.748.148.548.3PTV Score2.52.32.02.0Dmean (Gy)Heart7.28.47.31.0Contralateral Lung4.35.16.40.4Ipsilateral Lung13.513.714.59.3Contralateral Breast3.53.64.30.0OAR Score2.33.33.21.1 Citation Format: Wassim El Amine, Laurent Bartolucci, Camille Adrien, Marie Lejars, Alain Fourquet, Marion Vaillant, Magalie Robilliard, Emilie Costa, Alejandro Mazal, Farid Goudjil, Youlia Kirova. Intensity modulated radiotherapy (IMRT) for breast and lymph node irradiation [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-32.
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- 2020
43. REDD1 deficiency protects against nonalcoholic hepatic steatosis induced by high‐fat diet
- Author
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Karine Dumas, Pascal Peraldi, Faustine Pastor, Chaima Ayachi, Rodolphe Anty, Sandra Lacas-Gervais, Nathalie Vaillant, Stéphanie Patouraux, Philippe Gual, Albert Tran, Jean-François Tanti, Laurent Yvan-Charvet, Sophie Giorgetti-Peraldi, Mireille Cormont, François Bertrand Favier, Stéphanie Bonnafous, Jerome Gilleron, Université Côte d'Azur, Inserm, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 'Cellular and Molecular Pathophysiology of Obesity and Diabetes', Université Côte d'Azur, Centre Commun de Microscopie Appliquée (CCMA), Dynamique Musculaire et Métabolisme (DMEM), Université de Montpellier (UM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA), Université Côte d'Azur, Inserm, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 'Haematometabolism in Diseases', Université Côte d'Azur, Inserm, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 'Chronic Liver Diseases Associated with Steatosis', Fédération d'Hépatologie, Centre Hospitalier Universitaire de Nice (CHU Nice), ANR-15-IDEX-0001,UCA JEDI,Idex UCA JEDI(2015), ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), Tanti, Jean-François, Idex UCA JEDI - - UCA JEDI2015 - ANR-15-IDEX-0001 - IDEX - VALID, Centres d'excellences - Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie - - SIGNALIFE2011 - ANR-11-LABX-0028 - LABX - VALID, Université Nice Sophia Antipolis (1965 - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
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Adult ,Male ,0301 basic medicine ,autophagy ,obesity ,medicine.medical_specialty ,Diet, High-Fat ,Chronic liver disease ,Biochemistry ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Nonalcoholic fatty liver disease ,Mitophagy ,Genetics ,medicine ,Animals ,Humans ,Molecular Biology ,Beta oxidation ,Cells, Cultured ,[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,2. Zero hunger ,Carnitine O-Palmitoyltransferase ,business.industry ,hepatic steatosis ,Autophagy ,REDD1 ,Lipid metabolism ,[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,medicine.disease ,Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ,3. Good health ,Fatty Acid Synthase, Type I ,030104 developmental biology ,Endocrinology ,Female ,Steatosis ,Sterol Regulatory Element Binding Protein 1 ,business ,Gene Deletion ,Stearoyl-CoA Desaturase ,030217 neurology & neurosurgery ,Transcription Factors ,Biotechnology - Abstract
International audience; Nonalcoholic fatty liver disease is a chronic liver disease which is associated with obesity and insulin resistance. We investigated the implication of REDD1 (Regulated in development and DNA damage response-1), a stress-induced protein in the development of hepatic steatosis. REDD1 expression was increased in the liver of obese mice and morbidly obese patients, and its expression correlated with hepatic steatosis and insulin resistance in obese patients. REDD1 deficiency protected mice from the development of hepatic steatosis induced by high-fat diet (HFD) without affecting body weight gain and glucose intolerance. This protection was associated with a decrease in the expression of lipogenic genes, SREBP1c, FASN, and SCD-1 in liver of HFD-fed REDD1-KO mice. Healthy mitochondria are crucial for the adequate control of lipid metabolism and failure to remove damaged mitochondria is correlated with liver steatosis. Expression of markers of autophagy and mitophagy, Beclin, LC3-II, Parkin, BNIP3L, was enhanced in liver of HFD-fed REDD1-KO mice. The number of mitochondria showing colocalization between LAMP2 and AIF was increased in liver of HFD-fed REDD1-KO mice. Moreover, mitochondria in liver of REDD1-KO mice were smaller than in WT. These results are correlated with an increase in PGC-1α and CPT-1 expression, involved in fatty acid oxidation. In conclusion, loss of REDD1 protects mice from the development of hepatic steatosis.
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- 2020
44. Survival and relative dose intensity of 5-fluorouracil, oxaliplatin and irinotecan in real-life treatment of metastatic colorectal cancer
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Maud Basso, Karine Salignon, Willy Vaillant, and Ilfad Blazevic
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,real-life ,Colorectal cancer ,medicine.medical_treatment ,Population ,relative dose intensity ,colorectal cancer ,chemotherapy ,survival ,03 medical and health sciences ,0302 clinical medicine ,FOLFOX ,Internal medicine ,medicine ,Radiology, Nuclear Medicine and imaging ,education ,Original Paper ,education.field_of_study ,Chemotherapy ,business.industry ,Hazard ratio ,medicine.disease ,digestive system diseases ,Oxaliplatin ,Irinotecan ,030104 developmental biology ,030220 oncology & carcinogenesis ,FOLFIRI ,Medicine ,business ,medicine.drug - Abstract
Introduction Combinations of 5-fluorouracil/leucovorin (5-FU/LV) with oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) are part of standard treatments for metastatic colorectal cancer (mCRC). For these molecules, the impact of a low relative dose intensity (RDI) on survival is not sufficiently known in real-life. Material and methods Data were collected retrospectively from patients treated in our center for an unresectable mCRC with FOLFOX or FOLFIRI as a first-line treatment. To study the impact on progression-free survival (PFS) and overall survival (OS), patients were divided into high and low RDI according to the median RDI of 5-FU on one end, and the median RDI of oxaliplatin or irinotecan (OXA-IRI) on the other. Results In our population of 75 patients, the median age was 67.1 years and 77% of patients were treated with FOLFIRI. Patients with high RDI for OXA-IRI had better PFS compared to patients with low RDI (hazard ratio [HR], 0.58; p = 0.03). There was no statistically significant difference in PFS for patients with high RDI for 5-FU (HR, 0.66; p = 0.09). No difference was found in overall survival according to the RDI of OXA-IRI (HR, 0.72; p = 0.18) or 5-FU (HR, 0.77; p = 0.29). RDI had no significant impact on toxicities. Conclusions Our analysis suggests that a low RDI of oxaliplatin and irinotecan has a negative effect on PFS. RDI had no significant effect on OS in our cohort. The clinical benefit of maintaining high RDI in these patients appears low.
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- 2020
45. Stratégies thérapeutiques dans le cancer bronchique non à petites cellules ALK positif de stade IV
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P. Hofman, C. Mascaux, A. Tiotiu, O. Menard, Y. Billon, and P. Vaillant
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Pulmonary and Respiratory Medicine ,Oncology ,Alectinib ,medicine.medical_specialty ,Brigatinib ,Crizotinib ,Ceritinib ,business.industry ,medicine.disease ,Lorlatinib ,03 medical and health sciences ,0302 clinical medicine ,030228 respiratory system ,Tumor progression ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Anaplastic lymphoma kinase ,030212 general & internal medicine ,business ,Lung cancer ,medicine.drug - Abstract
Anaplastic lymphoma kinase (ALK) rearrangement is a therapeutically targetable oncogenic driver found in 5% of patients with non-small-cell lung cancer (NSCLC). The objective of this paper is to synthesise current knowledge on ALK rearrangement and its impact on the management of advanced NSCLC. Several inhibitors of the tyrosine kinase of ALK (crizotinib, ceritinib, alectinib) have been approved as first line therapies in patients with advanced ALK positive NSCLC, which are associated with a better median progression-free survival than conventional chemotherapy. Unfortunately, the emergence of drug resistance leads to tumor progression. In patients with oligoprogressive disease if local ablative therapy can be effected, continuing with the same ALK tyrosine kinase inhibitor is one option. In patients with progression, clinicians may consider switching to another therapy. Rebiopsy of the tumor or liquid biopsy could be attempted to identify the mechanisms of resistance and to customize ALK-target therapy. The emergence of crizotinib drug resistance has prompted the development of next generation drugs including ceritinb, alectinib, brigatinib and lorlatinib. The ability to quickly develop targeted therapies against specific oncogenic drivers will require close co-operation between pathologists, pulmonologists and oncologists in the future to keep pace with drug discoveries and to define optimal therapeutic strategies.
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- 2019
46. Re: Surgical tracheotomy
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F. Tankéré, E. Savier, E. Romanelli, and J.-C. Vaillant
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medicine.medical_specialty ,Tracheotomy ,business.industry ,General surgery ,medicine.medical_treatment ,Medicine ,Humans ,General Medicine ,business - Published
- 2021
47. Unravelling data for rapid evidence-based response to COVID-19: a summary of the unCoVer protocol
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José M Castellano, Marek Majdan, In-Hwan Oh, John Kelleher, Saša Missoni, Natalija Novokmet, João Silva, Guy Fagherazzi, Marianne Van Der Sande, Silvia Riva, Joan B Soriano, David M. Pereira, Julio Ancochea, Michel Vaillant, Jörn Klein, Brecht Devleesschauwer, Patrick Soentjens, Ernestina Menasalvas, Justo Menéndez, Antigona Carmen Trofor, Olga Sánchez-Pernaute, Mihaela Lupse, Dora Buonfrate, Zubair Kabir, Miguel Górgolas, Paula Villares, Lucia Maria Lotrean, Lucía Llanos, Costas Tsiamis, Seval Akgün, Tamara Ursini, José L. Peñalvo, Jelena Dimnjaković, Marija Švajda, Tamara Poljičanin, Jelena Sarac, Enisa Ademović, Ana Lúcia Baltazar, Miran Čoklo, Paula Andrea Diaz Valencia, João C. Fernandes, Enrique Javier Gómez, Paul Hynds, Polychronis Kostoulas, Lucía Llanos Jiménez, Paul Nguewa, Georgie O’Sullivan, Miguel Reina Ortiz, Gloria Soriano, Joan B. Soriano, Fernando Spilki, Mary Elizabeth Tamang, Sabrina Van Ierssel, Jakov Vuković, José M. Castellano, James Cottam, Hanne Van Tiggelen, José Barberán, Mercedes Villareal, Nerea Ruiz del Árbol, Alberto Estirado, Alberto Blázquez Herranz, David Fernandez Lobón, Paloma Chausa, David M Pereira, Morteza Hosseini, Elizabeth Hunter, Brendan Palmer, Milena Man, Mira Florea, Andrei Tudor Cernomaz, Radu Adrian Crisan-Dabija, Cristina Grigorescu, João C Fernandes, Daria Rabarova, Adriana Krsakova, Jaroslava Brnova, Janka Prnova, Jaroslav Slany, Dominika Plancikova, Nisa Boukichou Abdelkader, Adrián Peláez, Elena Ávalos, Gorane Iturricastillo, Arnoldo Santos Oviedo, Sergio Luis Lima, Antonio Herrero, Pablo Minguez, Olympia Lioupi, Eleftherios Meletis, Konstantinos Pateras, Mustafa Asfari, Nicoletta De Santis, Petronille Bogaert, Koen Blot, Miriam Saso, Mathil Vandromme, Ivan Pristas, Marko Brkic, Luka Bočkor, Ivan Dolanc, Antonija Jonjić, Iva Šunić, Tugba Gürgen Erdogan, Süleyman Çetinkünar, Cenk Belibağlı, Kübra Demir, Mustafa Görür, Turgut Bulut, K R NayarSilvia Riva, Carlo Giordani, Petra Golin, Oh In-Hwan, Seok Jun Yoon, Lina Ruíz, Juan Pablo Pérez Bedoya, Oscar Ignacio Mendoza, Camilo Hincapie, Boris Rodriguez, Noël Barengo, Juliane Deise Fleck, Matheus Nunes Weber, Lejla Burnazović-Ristić, Semra Čavaljuga, Džan Ahmed Jesenković, Lejla Džananović, Veritati - Repositório Institucional da Universidade Católica Portuguesa, and UnCoVer Network
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medicine.medical_specialty ,Evidence-based practice ,Exploit ,Interoperability ,Information repository ,computer.software_genre ,03 medical and health sciences ,0302 clinical medicine ,Research Methods ,Medicine and Health Sciences ,Humans ,Medicine ,030212 general & internal medicine ,Statistics & research methods ,Pandemics ,030304 developmental biology ,Protocol (science) ,0303 health sciences ,Public health ,real-world data ,SARS-CoV-2 ,business.industry ,Application server ,COVID-19 ,General Medicine ,Data science ,public health ,statistics & research methods ,3. Good health ,Europe ,Clinical trial ,Human medicine ,business ,computer - Abstract
IntroductionunCoVer—Unravelling data for rapid evidence-based response to COVID-19—is a Horizon 2020-funded network of 29 partners from 18 countries capable of collecting and using real-world data (RWD) derived from the response and provision of care to patients with COVID-19 by health systems across Europe and elsewhere. unCoVer aims to exploit the full potential of this information to rapidly address clinical and epidemiological research questions arising from the evolving pandemic.Methods and analysisFrom the onset of the COVID-19 pandemic, partners are gathering RWD from electronic health records currently including information from over 22 000 hospitalised patients with COVID-19, and national surveillance and screening data, and registries with over 1 900 000 COVID-19 cases across Europe, with continuous updates. These heterogeneous datasets will be described, harmonised and integrated into a multi-user data repository operated through Opal-DataSHIELD, an interoperable open-source server application. Federated data analyses, without sharing or disclosing any individual-level data, will be performed with the objective to reveal patients’ baseline characteristics, biomarkers, determinants of COVID-19 prognosis, safety and effectiveness of treatments, and potential strategies against COVID-19, as well as epidemiological patterns. These analyses will complement evidence from efficacy/safety clinical trials, where vulnerable, more complex/heterogeneous populations and those most at risk of severe COVID-19 are often excluded.Ethics and disseminationAfter strict ethical considerations, databases will be available through a federated data analysis platform that allows processing of available COVID-19 RWD without disclosing identification information to analysts and limiting output to data aggregates. Dissemination of unCoVer’s activities will be related to the access and use of dissimilar RWD, as well as the results generated by the pooled analyses. Dissemination will include training and educational activities, scientific publications and conference communications.
- Published
- 2021
48. 'I Can’t Go Far': Perceptions and Experiences of Heart Failure Patients Regarding Physical Activity: A Qualitative Study Using Semistructured Face-to-Face Interviews
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Frédéric Dutheil, Helene Vaillant Roussel, Elodie Lafarge, Thibault Menini, Philippe Vorilhon, Martial Bernard, Elodie Charuel, Benoit Cambon, Faculté de Médecine - Clermont-Auvergne (FM - UCA), Université Clermont Auvergne (UCA), AutomédiCation aCcompagnement Pluriprofessionnel PatienT (ACCePPT), Faculté de Pharmacie - Clermont-Auvergne (FP - UCA), Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Service Santé Travail Environnement [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Clermont-Ferrand
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Gerontology ,media_common.quotation_subject ,Physical activity ,[SHS.PSY]Humanities and Social Sciences/Psychology ,03 medical and health sciences ,0302 clinical medicine ,Arts and Humanities (miscellaneous) ,Face to face interview ,Perception ,medicine ,Humans ,030212 general & internal medicine ,Exercise ,Qualitative Research ,media_common ,Heart Failure ,030505 public health ,Public Health, Environmental and Occupational Health ,medicine.disease ,3. Good health ,Heart failure ,Chronic Disease ,Life expectancy ,Quality of Life ,0305 other medical science ,Psychology ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Qualitative research - Abstract
Background Participation in regular physical activity (RPA) is beneficial to the quality of life and life expectancy of patients with chronic heart failure (CHF). However, it is inadequate in many patients. Aims To determine the factors that influence the practice of RPA in patients with CHF managed in general practice. Method This was a qualitative study using semistructured, individual face-to-face interviews. Patients with CHF (New York Heart Association Stages 1–3) capable of participating in RPA were enrolled by their general practitioner. A longitudinal and transversal inductive thematic analysis was performed by two researchers. Results Five themes emerged from the 19 interviews that were conducted. Poor knowledge of the disease and the benefits of participating in RPA, as well as the lack of motivation or enjoyment, in particular due to the absence of previous participation, were considered significant obstacles. Fear associated with CHF or other comorbidities was also an obstacle. Attendance at a rehabilitation center, family and social circles, and having a pet all appeared to be beneficial. Family and friends were important for motivating the patient to participate in an activity but could also be an obstacle when they were overprotective. Conclusion This study helps highlight the difficulties for patients with CHF associated with participation in RPA. Despite the obstacles, there are enabling factors on which the general practitioner may rely to motivate their patients.
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- 2021
49. Eltrombopag in adult patients with immune thrombocytopenia in the real-world in France, including off-label use before 6 months of disease duration: The multicenter, prospective ELEXTRA study
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Julia Moeglin, Morgane Mourguet, Laurent Alric, Laure Swiader, Suzanne Tavitian, Jean-Marc Durand, Sylvie Ollier, Aline Moignet‐Autrel, Karen Delavigne, Miguel Carreiro, Pierre Cougoul, Jean Estelle, Sylvain Audia, Benjamin De Sainte Marie, Veronique Remy, Xavier Delbrel, Samuel Deshayes, Francis Gaches, Helene Hennique, Lorraine Leplay, Gaetan Sauvetre, Antoine Briantais, Cécile Borel, Kamel Laribi, Martin Michaud, Stéphane Cheze, Sondess Hadj‐Khelifa, Guillaume Martin‐Blondel, Geoffrey Urbanski, Brice Castel, Guillaume Moulis, Fanny Nuccio, Soraya Leclerc-Teffahi, Odile Beyne‐Rauzy, Benjamin Hebraud, Aurelie Godel‐Labouret, Pierre Duffau, Sarah Khatibi, Baptiste Andre, Gregory Pugnet, Daniel Adoue, Julie Seguier, Clement Gaudin, Marc Michel, Myriam Aroichane, Laurent Prudhomme, Margaux Lafaurie, Manuela Rueter, Philippe Montane De La Roque, Natacha Brun, Aurelie Saunier, Julie Graveleau, Johanne Germain, Willy Vaillant, Agnès Sommet, Maryse Lapeyre-Mestre, Delphine Bonnet, Stephane Sire, Yann Leveneur, Caroline Soubrier, Alina Danu, Veronique Veit, Patrick Giraud, François Lifermann, Gwenola Maigne, Jean-François Viallard, Clothilde Martel, Nicolas Limal, Delphine Brechemier, Frederique Roy‐Peaud, Serge Madaule, Laurent Sailler, Thibault Comont, Benoit Faucher, Laurent Balardy, Carine Courtault, Claire Dingremont, Jean-Robert Harlé, Sophie Arista, Mikael Ebbo, Bertrand Godeau, Jeremie Dion, Bernard Bonnotte, Irène Machelart, Matthieu Mahévas, Nicolas Schleinitz, Arnaud Saint‐Lezer, Corentin Orvain, Christian Recher, Patrick Rispal, and Bertrand Lioger
- Subjects
Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Disease duration ,Eltrombopag ,Off-label use ,Benzoates ,chemistry.chemical_compound ,medicine ,Humans ,Prospective Studies ,Aged ,Purpura, Thrombocytopenic, Idiopathic ,Adult patients ,business.industry ,Hematology ,Off-Label Use ,Middle Aged ,Immune thrombocytopenia ,Hydrazines ,Treatment Outcome ,chemistry ,Pyrazoles ,Female ,France ,business - Published
- 2021
50. Mammary tumour cells remodel the bone marrow vascular microenvironment to support metastasis
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Geoffrey J. Lindeman, Kellie A. Mouchemore, Robin L. Anderson, Yunshun Chen, Elliot Surgenor, Bhupinder Pal, Joel S. Rimes, Raymond K H Yip, Andrew J. Murphy, Edwin D. Hawkins, Bianca D. Capaldo, Gordon K. Smyth, François Vaillant, and Jane E. Visvader
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Science ,General Physics and Astronomy ,Bone Neoplasms ,Breast Neoplasms ,Mammary Neoplasms, Animal ,Biology ,Cellular imaging ,General Biochemistry, Genetics and Molecular Biology ,Article ,Bone and Bones ,Metastasis ,Mice ,Breast cancer ,Imaging, Three-Dimensional ,Bone Marrow ,Granulocyte Colony-Stimulating Factor ,Receptors, Colony-Stimulating Factor ,medicine ,Tumor Microenvironment ,Animals ,Humans ,Neoplasm Metastasis ,Receptor ,Multidisciplinary ,Bone metastasis ,Neoplasms, Second Primary ,General Chemistry ,medicine.disease ,Haematopoiesis ,medicine.anatomical_structure ,Cancer cell ,Cancer research ,Disease Progression ,Bone marrow ,Blood vessel - Abstract
Bone marrow is a preferred metastatic site for multiple solid tumours and is associated with poor prognosis and significant morbidity. Accumulating evidence indicates that cancer cells colonise specialised niches within the bone marrow to support their long-term propagation, but the precise location and mechanisms that mediate niche interactions are unknown. Using breast cancer as a model of solid tumour metastasis to the bone marrow, we applied large-scale quantitative three-dimensional imaging to characterise temporal changes in the bone marrow microenvironment during disease progression. We show that mouse mammary tumour cells preferentially home to a pre-existing metaphyseal domain enriched for type H vessels. Metastatic lesion outgrowth rapidly remodelled the local vasculature through extensive sprouting to establish a tumour-supportive microenvironment. The evolution of this tumour microenvironment reflects direct remodelling of the vascular endothelium through tumour-derived granulocyte-colony stimulating factor (G-CSF) in a hematopoietic cell-independent manner. Therapeutic targeting of the metastatic niche by blocking G-CSF receptor inhibited pathological blood vessel remodelling and reduced bone metastasis burden. These findings elucidate a mechanism of ‘host’ microenvironment hijacking by mammary tumour cells to subvert the local microvasculature to form a specialised, pro-tumorigenic niche., The visualisation of the bone metastasis process in a spatial temporal manner is lacking. Here, the authors use three-dimensional quantitative imaging and show that mouse mammary tumour cells preferentially home to endothelial subtype type H vessels within the bone marrow and remodel this vasculature by producing granulocyte-colony stimulating factor.
- Published
- 2021
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